Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 9th Edition

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Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases
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Contributors
Preface to the 9th Edition
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Contributors
Preface to the 9th Edition
I Basic Principles in the Diagnosis and Management of Infectious Diseases
A Microbial Pathogenesis
1 A Molecular Perspective of Microbial Pathogenicity
Attributes of Microbial Pathogens
Evolution of Bacterial Pathogenicity
Regulation of Bacterial Pathogenicity
Close Encounters: Pathogens as Cell Biologists
Identification and Characterization of Virulence Genes
Molecular Microbiology at the Bedside: Pathogen Detection, Pathogen Discovery, and Genomic Profiling
Dedication
Key References
References
2 The Human Microbiome of Local Body Sites and Their Unique Biology
Defining the Human Microbiome
The Human Microbiome as a Complex Ecosystem Composed of Multiple Body Site Habitats and Niches
From Whence and When Do Our Microbiomes Come?
Oral Microbiome
Associations Between Oral Microbiota and Disease States
Skin and Nasopharynx
Airway and Pulmonary Microbiome
Gastrointestinal Tract
Esophagus
Stomach
Intestine (Small and Large)
Vaginal Microbiome
Bacterial Vaginosis: An Example of a Prevalent Pathobiont in the Vaginal Microbiome
Group B Streptococcus
The Human Microbiome During Pregnancy
Summary and Future Directions
Key References
References
3 Prebiotics, Probiotics, and Synbiotics
Short View Summary
Issues Regarding the Complexity and Variability of Probiotics
Clinical Studies of Probiotics
Proposed Mechanisms of Action of Probiotics
Potential Adverse Effects of Probiotic Therapy
Fecal Microbiota Transplant for Infectious Conditions Other Than Clostridioides Difficile Infection
Summary and Future Directions
Key References
References
B Host Defense Mechanisms
4 Innate (General or Nonspecific) Host Defense Mechanisms
Physical and Chemical Barriers to the Entry of Microorganisms Into the Body
Skin
Mucous Membranes
Respiratory Tract
Gastrointestinal Tract
Genitourinary Tract
Eye
Innate Immune Sensing of Invading Pathogens
Phagocytosis
Autophagy
The Inflammatory Response
Cytokines and Chemotaxis
Pathogen Interference With Innate Immune Responses
Key References
References
5 Adaptive Immunity
Short View Summary
Immunoglobulin Structure
Basic Antibody Structure
F(ab′)2, Fab, and Fc Pieces
Antigen Binding, Affinity, and Avidity
Immunoglobulin Classes
Immunoglobulin M
Immunoglobulin G
Immunoglobulin A
Immunoglobulin D
Immunoglobulin E
Effector Functions Mediated by Antibodies
Blocking or Neutralization
Complement Activation
Opsonization
Antibody-Dependent Cellular Cytotoxicity
Direct Antibody-Mediated Antimicrobial Functions
Antibody-Mediated Catalysis
Kinetics of Antibody Production and Diagnosis of Infections
Laboratory Measurement of Antibodies
Quantification of Total Immunoglobulin
Serum Protein Electrophoresis for Monoclonal Gammopathies
Measurement of Functional Antibody
Western Blot
Agglutination and Complement Fixation
Immunofluorescence and Immunohistochemistry
Enumeration of Antibody-Producing B Cells: The ELISPOT Assay
Assays to Measure Antigen
Measurement of Immune Complexes
B-Cell Maturation and Immunoglobulin Production
DNA Rearrangement and Generation of Diverse Antigen-Binding Sites
Deletion of Autoreactive Clones
Antigen Stimulation: First Signal
Coreceptors Amplify or Suppress Antigen Signaling
Second Signals and Interactions Between B Cells and T Cells
How B Cells Find and Activate T Cells
T-Cell–Independent Antigens
Downregulation of Antibody Production
B1 Cells
Antibody-Mediated Pathology
Gell and Coombs Classification of Hypersensitivity Responses
Type I Hypersensitivity
Type II Hypersensitivity
Origin of Autoreactive Antibodies
Type III Hypersensitivity
Hypergammaglobulinemia
Immunodeficiencies
Immunoglobulin A Deficiency
Agammaglobulinemias
Hyper–Immunoglobulin M Syndrome
Common Variable Immunodeficiency
Immunoglobulin G Subclass Deficiencies
Selective Immunodeficiencies
Combined T-Cell and B-Cell Defects
Malignancies
Therapeutic Uses of Antibodies
Passive Immunization
Intravenous Immune Globulin Replacement
Monoclonal Antibodies
Key References
References
6 Cell-Mediated Defense Against Infection
Short View Summary
T-Cell Subsets and Phenotypic Diversity
CD4 T Cells
Th1 T Cells
Th2 T Cells
Th17 T Cells
T-Regulatory Cells
Helper T-Follicular Cells
Plasticity of Helper T-Cell Subsets
CD8 T Cells
NKT Cells and T Cells With a Restricted αβ TCR Repertoire
γδ T Cells
T-Cell Memory
T-Cell Development and Lymphoid Tissue Organization
Thymic Selection of CD4 and CD8 T Cells
Lymphoid Anatomy
Lymph Nodes
Spleen
Mucosa-Associated Lymphoid Tissue
T-Cell Activation
Organization of the Major Histocompatibility Complex
Antigen Presentation to T Lymphocytes via MHC Class I
MHC Class I Structure
MHC Class I Antigen-Processing Pathway
Viral Interactions With the MHC Class I Antigen-Processing Pathway
MHC Class I Cross-Presentation
Antigen Presentation to T Lymphocytes via MHC Class II
MHC Class II Structure
MHC Class II Antigen-Processing Pathway
CD1 and Antigen Presentation
Innate Immune Recognition: Setting the Stage for T-Cell Responses
Molecular Recognition of Microbial Products
Toll-Like Receptors
NOD-Like Receptors, RIG-I–Like Receptors, the Cyclic GMP-AMP Synthase–Stimulator of Interferon Genes Sensing Pathway, and the Inflammasome
C-Type Lectin Receptors
Links Between Innate Immune Recognition and Adaptive Immune Responses
Dendritic Cells
Microbial Pathogenesis and the Cellular Immune System
Viral Infections
Infections With Intracellular Bacteria and Fungi
Phagosomal Pathogens
Cytoplasmic Pathogens
Infections With Extracellular Bacteria and Fungi
Primer on Basic Immunologic Techniques
Characterizing and Measuring Pathogen-Specific Immunity
Key References
References
7 Mucosal Immunity
Short View Summary
Specialization of Host Responses in Mucosal Tissues
The Challenge
Adaptation of Mucosal Immune Responses
Microbial Communities and Development of Mucosal Immune Responses
Induction of Mucosal Immune Responses
Epithelial Cell Responses and Immunophysiology
Antigen-Presenting Cells
Innate Lymphoid Cells
Sensing Mucosal Microbiota
Sensing Metabolites
Discrimination Between a Commensal and a Pathogen
Adaptive Immunity to Mucosal Stimulation
Immunologic Homeostasis in Mucosal Tissues
When Mucosal Responses Go Wrong
Mucosal Host Response Defines Pathogenicity
Good Bugs, Bad Bugs, and the Hygiene Hypothesis
Mucosal Immunization
Role of Mucosal Immunity: Beyond the Mucosa
Conclusions
Key References
References
8 Granulocytic Phagocytes
Neutrophils
Development
Emergency Granulopoiesis
Mitotic and Postmitotic Cells
Morphologic and Structural Characteristics
Azurophilic Granules
Peroxidase-Negative Granules
Nucleus and Actin Cytoskeleton
Organelles in the Cytoplasm
Surface Receptors
Homeostasis of the Circulating Neutrophil Population
Distribution of Neutrophils
Inflammatory Response
Priming
Step 1: Neutrophil Recruitment
Selectin-Mediated Adhesion and Rolling
β2-Integrin–Mediated Cell-Cell Interaction
Tissue Migration
Production of Inflammatory Mediators
Role of Chemokines in Neutrophil Recruitment
Step 2: Phagocytosis
Opsonins
Phagocytic Receptors
Ingestion
Step 3: Fate of the Ingested Microbe
Respiratory Burst
Reactive Oxygen Species
NADPH Oxidase (Respiratory Burst Oxidase)
Translocation of Cytosolic Components
p40phox
Rac2
Nonphagocyte Oxidases: The NOX Protein Family
Degranulation
Step 4: Resolution of the Inflammatory Response
Apoptosis
Proinflammatory Molecules Alter Apoptosis
Microbial Pathogens Influence Neutrophil Fate
Neutrophils as “Trojan Horses”
Bioactive Lipid Mediators
Microbicidal Mechanisms
Intraphagosomal Killing of Microbes
Oxygen-Dependent Killing of Microbes
Oxygen-Independent Killing of Microbes
Extracellular Microbicidal Activity
Neutrophils and Microbial Evasion of Host Defense
Microbial Responses to Neutrophils
Microbial Targeting of Neutrophil Surface Molecules
Survival of Microbes After Ingestion by Neutrophils
Eosinophils
Development and Characteristics
Eosinophil Surface Receptors
Eosinophil Granules
Recruitment From Circulation
Role in Host Defense
Moderation of Type I Hypersensitivity Reactions
Eosinophil-Mediated Tissue Injury
Key References
References
9 Complement and Deficiencies
Short View Summary
Complement Synthesis, Catabolism, and Distribution
Complement Activation
Overview: C3, the Linchpin of the Complement System
Generation of the Classical-Pathway C3 Convertase
Generation of the Alternative-Pathway C3 Convertase
The “Tickover” Model
The Properdin-Directed Model
Assembly of the Membrane Attack Complex
Regulation of Complement Activation
Regulation of C1 Activation
Regulation of the C3 Convertases
Regulation of the Membrane Attack Complex
Basis for Discriminating Between Host and Microbial Cell Surfaces
Complement Receptors
Families of Complement Proteins
Complement-Mediated Functions
Elimination of Pathogens
Modulation of Adaptive Immune Responses
Clearance of Immune Complexes and Apoptotic Cells
Complement and Metabolism
Complement and Cancer
Complement in Tissue Regeneration and Organogenesis
Microbial Interactions With the Complement System
Complement Deficiency States
Incidence
General Aspects of the Molecular Basis for Complement Deficiencies
Classical-Pathway Deficiencies
Clinical Aspects
Immune Disorders
Pathophysiologic roles for complement in systemic lupus erythematosus.
Infectious Diseases
Molecular Aspects
Lectin-Pathway Deficiencies
Deficiency of Mannose-Binding Protein
Clinical Aspects
Molecular Aspects
Deficiency of Ficolin-3
Deficiencies of Collectin 11 (CL-K1) and MASP-1
Clinical Aspects
Molecular Aspects
Deficiency of Mannose-Binding Protein–Associated Serine Protease 2 (MASP-2)
Alternative-Pathway Deficiencies
Clinical Aspects
Molecular Aspects
C3 Deficiency
Clinical Aspects
Molecular Aspects
Late Complement Component Deficiencies
Clinical Aspects
Meningococcal Disease in Complement Deficiency
Molecular Aspects
Deficiencies of Complement Regulatory Proteins
Hereditary Angioedema: C1 Inhibitor Deficiency
Factor H Deficiency
Clinical Aspects: Membranoproliferative Glomerulonephritis Type II
Clinical Aspects: Atypical Hemolytic-Uremic Syndrome
Clinical Aspects: Age-Related Macular Degeneration
CD59 Deficiency: Paroxysmal Nocturnal Hemoglobinuria
Complement in Disease States
Infectious Diseases
Rheumatologic Disorders
Renal Disorders
Evaluation and Treatment of Complement Disorders
Evaluation
Treatment
Acknowledgment
Key References
References
10 Human Genetics and Infection
Short View Summary
Magnitude of the Host Genetic Effect
Approaches
Diseases
Malaria
Mycobacterial Diseases
Viral Diseases
Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome
Persistent Hepatitis
Other Viral Diseases
Other Infectious Disease Phenotypes
Specific Susceptibility and Resistance Genes
Blood Groups
Human Leukocyte Antigens
Mannose-Binding Lectin
Toll-Like Receptor Pathway Genes
Evolutionary Perspective
Applications
Key References
References
11 Nutrition, Immunity, and Infection
Epidemiology of Malnutrition
Malnutrition and Immune Function
Specific Nutrients and Their Roles in Immunity
Fat-Soluble Vitamins
Vitamin A
Vitamin D
Vitamin E
Water-Soluble Vitamins
Vitamin C
Vitamin B6
Folate
Vitamin B12
Trace Metals
Zinc
Selenium
Iron
Fatty Acids
Overnutrition: Obesity and Infectious Diseases
Special Populations: Clinical Trials of Nutritional Supplementation to Reduce Infection Risk
Surgical and Critically Ill Patients
Total Parenteral Nutrition Versus Enteral Nutrition
Immunonutrition
Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome
Strategies to Combat Weight Loss and Wasting Associated With Human Immunodeficiency Virus
Macronutrient Supplementation
Micronutrient Supplementation
Older Adults
Nutritional Supplements in Older Adults: Effects on Immunity and Clinical Outcomes
Multivitamin and Trace Mineral Supplements
Vitamin E
Zinc
Host Nutritional Status and Pathogen Virulence
Acknowledgments
Key References
References
12 Evaluation of the Patient With Suspected Immunodeficiency
Short View Summary
Index of Suspicion
Initial Evaluation
Lymphocyte Immune Defects
T Cells and Cell-Mediated Immunity
B Cells and Humoral Immunity
Phagocyte Immune Defects: Neutrophils
Neutropenia
Chédiak-Higashi Syndrome
Leukocyte Adhesion Deficiency
Neutrophil-Specific Granule Deficiency
Myeloperoxidase Deficiency
Chronic Granulomatous Disease
Defects Affecting Phagocyte Signaling
Phagocyte and Lymphocyte Defects Affecting Mononuclear Cells
Hyperimmunoglobulin E–Recurrent Infection Syndrome (Job Syndrome)
GATA2 Deficiency
Complement-Mediated Immunity
Acquired Immunodeficiencies
Key References
References
C Epidemiology of Infectious Disease
13 Applied Epidemiology for the Infectious Diseases Physician
What Is Epidemiology?
What Can Epidemiology Tell the Infectious Disease Clinician?
The Epidemiologic Triad Model: Agent, Host, and Environment
The Sufficient-Component Cause Model of Epidemiology
Other Methods to Characterize Infection Transmission
Descriptive Epidemiology
Analytic Epidemiology
Experimental Studies
Observational Studies
Cohort Studies
Case-Control Studies
Cross-Sectional and Ecologic Studies
Determining the Appropriate Epidemiologic Study Design
Basic Biostatistics
Measures of Disease Frequency
Ratios, Proportions, and Rates
Incidence
Prevalence
Measures of Association
Two-by-Two Tables
Prevalence Ratio and Prevalence Odds Ratio
Statistical Significance
P Values
Confidence Intervals
Disease Surveillance
Classification of Surveillance
Disease Prevention
Disease Control: Quarantine and Isolation
Outbreak Investigation Primer
Outbreak Epidemiology
General
Key Outbreak Principles
Incubation Period
Epidemic Curves
Transmission Modes
Chains of Transmission
Types of Outbreaks
Foodborne Outbreaks
Nosocomial Outbreaks
Respiratory and Other Person-to-Person Outbreaks
Sexually Transmitted Outbreaks
Zoonotic and Vector-Borne Outbreaks
Outbreak Investigation and Response
Consequences of an Outbreak
Key References
References
14 Emerging and Reemerging Infectious Disease Threats
Short View Summary
Infectious Causes of Chronic Diseases
Factors That Favor Disease Spread
Antimicrobial Resistance
Acute Respiratory Tract Infections
Human Metapneumovirus
Human Coronaviruses
Human Bocaviruses
Emerging Influenza Viruses
Reservoirs of Influenza A
Influenza A and Pandemics
Novel Influenza A Viruses
Influenza A(H5N1)
Influenza A(H5N6)
Influenza A(H7N9)
Other Influenza A Virus Subtypes
Variant Influenza A Infections From Swine
Influenza Risk Assessment
Enteric Diseases
Routes of Transmission for Enteric Pathogens
International Spread: Cholera in the Western Hemisphere
Evolution of Enteric Pathogens
Noroviruses
Future Trends
Vector-Borne Diseases
The Aedes-Transmitted Viruses: Dengue, Zika, Yellow Fever, and Chikungunya
Dengue
Zika
Yellow Fever
Chikungunya
Plasmodium vivax, Plasmodium knowlesi, and Zoonotic Malaria
Tick-borne Pathogens
Ebola and Marburg Hemorrhagic Fevers
Conclusion: Controlling the Threats
Acknowledgments
Key References
References
15 Bioterrorism
Defining Biological Warfare, Bioterrorism, and Biocrimes
History of Biological Weapons Development and Use in Warfare and Against Insurgencies
Pre–World War I Biological Weapons Development and Use
Development and Use of Biological Weapons During World War I
Development and Use of Biological Weapons During World War II
Biological Weapons in the Post–World War II Period Through the End of the Cold War
Offensive Biological Weapons Programs in the United States
Limiting Use of Biological Weapons: the Biological Weapons Convention
Monitoring and Compliance Under the Biological Weapons Convention
Civilian Research in the Soviet Union
Military Activities in the Soviet Union
Iraq’s Biological Weapons Program
History of Biological Weapons Use to Commit Acts of Bioterrorism
20th-Century Bioterrorism Against Humans: The Rajneeshee Cult
21st-Century Bioterrorism Against Humans: The Anthrax Letters
Limiting Development and Use of Biological Weapons by Terrorists
Classifications of Biological Agents of Concern
Formulation of the CDC List of Category A, B, and C Agents/Diseases of Bioterrorism
The CDC and NIAID Biodefense and Priority Pathogen Lists in Perspective
Dual Use Research of Concern, Gain-of-Function Research, and Synthetic Biology
Addressing the Highest Priority Biological Agents
Approval and Use of Medical Countermeasures for Priority Biological Agents
Emergency Use Authorization
The Animal Rule Use for Approval of Drugs, Vaccines, and Biologics
Clinical Aspects of High-Consequence Bioterrorism Pathogens
Variola (Smallpox) Virus
Bacillus anthracis
Clostridium botulinum Toxin
Yersinia pestis
Francisella tularensis
Rickettsia prowazekii
Burkholderia mallei
Burkholderia pseudomallei
Viral Hemorrhagic Fever Viruses
Bioterrorism Incidents
Clinical Provider Preparedness and Response
Supplementing Health Care Provider Resources
Supplementing MCMs With the Strategic National Stockpile
Health Care Facility Preparedness and Response
Public Health Preparedness and Response
Communication
Epidemiology
Laboratory Preparedness and Response
Surveillance
Acknowledgment
Key References
References
D Clinical Microbiology
16 The Clinician and the Microbiology Laboratory: Test Ordering, Specimen Collection, and Result Interpretation
Short View Summary
Microorganisms Hazardous to Laboratory Workers
Taxonomy
Infection Prevention and Control
Bacterial, Mycobacterial, and Fungal Identification
Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry
Antibacterial Susceptibility Testing
Antimicrobial Stewardship
Specimen Selection, Collection, Transportation, and Initial Processing
Specific Specimen Guidelines and Initial Laboratory Processing
Blood Cultures
Intravenous Catheter Tips
Cerebrospinal Fluid
Peritoneal, Pleural, and Pericardial Fluids
Bone and Joint Specimens
Skin and Soft Tissue Specimens
Respiratory Tract Specimens
Urine
Stool
Vaginitis and Vaginosis Diagnostics
Genital Lesions and Syphilis Diagnostics
Urethritis and Cervicitis Diagnostics
Helicobacter pylori Diagnostics
Mycobacterium tuberculosis Diagnostics
Acknowledgments
Key References
References
E Antiinfective Therapy
17 Principles of Antiinfective Therapy
Short View Summary
The Antibiotic Miracle: What We Are Fighting for
A Brief History of “Antibiotics”
The Power of Antibiotics: What We Stand to Lose Due to Resistance
The Societal Trust of Antibiotics Must Underpin Principles of Use
Antibiotics Are a Societal Trust
Fundamental Principles of Antibiotic Therapy
1. Proper Selection of Empirical Antibiotics Starts With an Accurate Differential Diagnosis That Includes Likely Bacterial Infection
2. Even in a Patient With a Bacterial Infection, Treat Only When Therapy Will Alter the Patient’s Clinical Course
3. Empirically Target Microbes That Cause the Diseases in the Differential Diagnosis
4. A Lower Threshold for Empirical Therapy Should Be Used in Critically Ill Patients
5. Host Factors Affect Breadth of Empirical Therapy by Altering Likely Microbial Causes of Infection
6. Pharmacokinetic-Pharmacodynamic Principles Can Influence Optimal Treatment
7. Deescalate Antibiotic Therapy Based on Microbiology Results and Clinical and Biomarker Responses
8. If Therapy Is Not Working, Consider Source Control and Alternative Diagnoses Before Blaming Resistance and Broadening Therapy
9. Distinguish New Infection From Failure of Initial Therapy
10. The Duration of Therapy Should Be Evidence Based and Short Course Whenever Possible
Controversial Principles of Antibiotic Therapy
The Greatly Misunderstood Dogma of Bactericidal Versus Bacteriostatic
Combination Therapy: The Good, the Bad, and the Ugly
The Good
The Good #1: Ensuring Adequate Empirical Coverage
The Good #2: Preventing Resistance Emergence
The Good #3: Improving Cure
Slow-growing infections/nonreplicating persisters.
Exotoxin-mediated necrotizing infections.
Eukaryotic infections.
“The Bad”: Redundant Definitive Therapy for Typical Bacterial Infections
“The Ugly”: Imperfect Data and Controversy
Controversy Over Superior Outcomes With Combination Therapy for Some Infections
Controversy Over Preventing Emergence of Resistance
Conclusions
Key References
References
18 Molecular Mechanisms of Antibiotic Resistance in Bacteria
Molecular Genetics of Antibiotic Resistance
Plasmids
Transposable Genetic Elements
DNA Integration Elements
Molecular Mechanisms of Antibiotic Resistance
Enzymatic Inhibition of Antimicrobial Activity
β-Lactamases
Extended-Spectrum β-Lactamases
TEM-derived β-lactamases.
SHV-derived β-lactamases.
CTX-M–derived extended spectrum β-lactamases.
OXA-derived β-lactamases.
AmpC β-lactamase enzymes.
Carbapenemases.
Gram-Positive Bacterial β-Lactamases
Anaerobic Bacteria
Contribution of β-Lactamases to β-Lactam Antibiotic Resistance
Aminoglycoside Resistance–Modifying Enzymes
Chloramphenicol Acetyltransferase
Macrolide-, Lincosamide-, Streptogramin-Inactivating Enzymes
Tetracycline Inactivation
Decreased Permeability of Bacterial Membranes
Outer Membrane Permeability
Inner Membrane Permeability
Promotion of Antibiotic Efflux
Tetracyclines
Macrolides and Streptogramins
β-Lactams
Fluoroquinolones
Altered Target Sites
Alteration of Ribosomal Target Sites
Macrolides, Lincosamides, Streptogramins
Tetracyclines
Aminoglycosides
Ketolides
Oxazolidinones
Alteration of Cell Wall Precursor Targets: Glycopeptides
Enterococci
Staphylococci
Alteration of Target Enzymes
β-Lactams
MRSA Resistance
Quinolones
Sulfonamides
Trimethoprim
Protection of Target Site
Tetracyclines
Fluoroquinolones
Overproduction of Target
Sulfonamides and Trimethoprim
Bypass of Antibiotic Inhibition
Resistance to Newer, Older, and Miscellaneous Agents
Oxazolidinones
Fosfomycin
Metronidazole
Multidrug-Resistance Mechanisms Among Bacteria
Control of Antibiotic Resistance
Key References
References
19 Pharmacokinetics and Pharmacodynamics of Antiinfective Agents
Short View Summary
Pharmacokinetics
Absorption
Distribution
Metabolism and Biotransformation
Elimination
Pharmacodynamics
Antimicrobial Potency
Pharmacodynamics Indices
Methodology for Study of Pharmacodynamics Effects of Antiinfective Agents
In Vitro Models
Animal Models
Clinical Trials
Concentration-Dependent Killing Agents
Time-Dependent Killing Agents
Postantibiotic Effect
Applied Clinical Pharmacokinetics and Pharmacodynamics
Higher-Dose Extended-Interval Dosing
Continuous-Infusion and Extended-Infusion Regimens
Dose-Refinement Considerations
Antiretroviral Pharmacodynamics
Defined Exposure (PK)-Response (PD) Relationships by Class
Protease inhibitors.
Nonnucleoside reverse transcriptase inhibitors.
Integrase strand transfer inhibitors.
Entry inhibitors.
Nucleoside reverse transcriptase inhibitors.
Antiretroviral Therapeutic Drug Monitoring
Alternative PK-PD Indices for Antiretroviral Therapy
Pharmacodynamics for Other Antiviral Drugs
Conclusions
Key References
References
20 Penicillins and β-Lactamase Inhibitors
Short View Summary
Penicillins
Chemistry
Mechanism of Action
Resistance Mechanisms
Classification
Pharmacologic Properties
Untoward Reactions
Clinical Use
Prophylactic Use
Properties of Individual Penicillins
Natural Penicillins
Penicillin G
Penicillin V
Penicillinase-Resistant Penicillins
Methicillin
Nafcillin
Isoxazolyl Penicillins
Aminopenicillins
Ampicillin
Amoxicillin
Carboxypenicillins
Ureidopenicillins
β-Lactamase Inhibitors and Inhibitor Combinations
Clavulanic Acid
Pharmacology
Adverse Reactions
Amoxicillin-Clavulanate
Sulbactam
Pharmacology
Adverse Reactions
Clinical Use
Tazobactam
Pharmacology
Adverse Reactions
Piperacillin-Tazobactam
Clinical Use
Ceftolozane-Tazobactam
Avibactam
Pharmacology
Adverse Reactions
Clinical Use
Vaborbactam
Pharmacology
Adverse Reactions
Clinical Use
Key References
References
21 Cephalosporins
Chemistry
Classification
Mechanism of Action
Spectrum of Activity
Mechanisms of Resistance
Pharmacologic Properties
Adverse Reactions and Toxicities
Major Clinical Uses of Cephalosporin Antibiotics
First-Generation Cephalosporins
Second-Generation Cephalosporins
Third-Generation Cephalosporins
Fourth-Generation Cephalosporins
Fifth-Generation Cephalosporins (MRSA-Active Cephalosporins)
Cephalosporin and β-Lactamase Inhibitor Combinations
Key References
References
22 Ertapenem, Imipenem, Meropenem, Doripenem, and Aztreonam
Short View Summary
Carbapenems
Chemistry
Mechanism of Action
Resistance
Carbapenem-Resistant Enterobacteriaceae
Antibacterial Activity
Pharmacology
Adverse Reactions
Clinical Use
Monobactams
Key References
References
23 Antibiotic Allergy
Pathophysiology
Approach to a Patient With an Antibiotic Allergy
Information to Be Obtained When Taking a History of Antibiotic Allergy
Clinical Manifestations
Immediate (Immunoglobulin E–Mediated or Pseudoallergic) Drug Reactions
Nonimmediate Drug Reactions
Drug Rash With Eosinophilia and Systemic Symptoms
Diagnosis and Management of Antibiotic Allergy
Tests for Immunoglobulin E–Mediated Immediate Reactions
Skin Testing: Prick and Intradermal Tests
In vitro Tests
Drug Challenge (Drug Provocation Tests)
Skin and in vitro Tests for Nonimmediate Reactions
Skin Testing: Delayed Intradermal and Patch Tests
In vitro Tests
Procedures to Induce Temporary Drug Tolerance
Drug Desensitization
“Treating Through” Antibiotic-Associated Exanthems
Drug Allergy to Specific Antimicrobial Agents
β-Lactams
Penicillins
Epidemiology
Evaluation of Penicillin Allergy as Part of Antimicrobial Stewardship
Pathophysiology
Clinical Manifestations
Diagnosis
Desensitization
Cephalosporins
Pathophysiology
Clinical Manifestations
Diagnosis
Desensitization
Carbapenems
Monobactams
Cross-Reactivity Among β-Lactams
Sulfonamides
Pathophysiology
Clinical Manifestations
Diagnosis
Treatment
Vancomycin
Fluoroquinolones
Macrolides
Aminoglycosides
Antibiotic Allergy and Antimicrobial Stewardship
Multiple Drug Intolerance Syndrome
Key References
References
24 Fusidic Acid
Short View Summary
Structure and Mechanism of Action
Antimicrobial Activity
Resistance
Administration and Dosing
Pharmacokinetics and Pharmacodynamics
Adverse Reactions
Clinical Uses
Key References
References
25 Aminoglycosides
Short View Summary
Chemistry
Mechanisms of Action
Mechanisms of Resistance
Antimicrobial Activity
Clinical Pharmacology
Nephrotoxicity
Experimental Nephrotoxicity
Clinical Nephrotoxicity
Ototoxicity
Cochlear Toxicity
Vestibular Toxicity
Neuromuscular Blockade
Clinical Indications
Bacteremia
Pneumonia
Intraabdominal Infections
Urinary Tract Infections
Cystic Fibrosis
Prophylaxis
Spectinomycin and Gonorrhea
Aminoglycosides in Orthopedic Surgery
Key References
References
26 Tetracyclines, Glycylcyclines, and Chloramphenicol
Short View Summary
Tetracyclines
Historical Overview and Classification
Structure and Mechanism of Action
Pharmacology
Administration and Dosing
Tetracycline
Doxycycline
Minocycline
Absorption and Bioavailability
Drug Distribution
Drug Elimination
Antimicrobial Activity
Gram-Positive Bacteria
Gram-Negative Bacteria
Atypical Bacteria
Spirochetes and Rickettsiae
Mycobacteria and Nocardia
Parasites
Clinical Uses
General
Respiratory Tract Infections
Gastrointestinal Tract Infections
Genitourinary Tract Infections
Spirochetal Infections
Malaria Treatment and Chemoprophylaxis
Other Infections
Acne Vulgaris
Antiinflammatory Uses
Bioterrorism Prophylaxis
Mechanism of Resistance
Adverse Reactions
General
Gastrointestinal Side Effects
Photosensitivity and Hyperpigmentation
Teeth and Bone
Hepatotoxicity
Nephrotoxicity
Neurotoxicity
Hypersensitivity Reactions
Teratogenicity
Drug and Food Interactions
Glycylcyclines
Tigecycline
Structure and Mechanism of Action
Pharmacology
Administration and Dosing
Absorption and Bioavailability
Drug Distribution
Drug Elimination
Antimicrobial Activity
Gram-Positive Bacteria
Gram-Negative Bacteria
Anaerobic Bacteria
Atypical Bacteria
Mycobacterium and Nocardia
Clinical Uses
Skin and Skin Structure Infections
Intraabdominal Infections
Respiratory Tract Infections
Other Uses
Mechanism of Resistance
Adverse Reactions
Gastrointestinal Side Effects
Hepatotoxicity and Pancreatitis
Other Side Effects
Increased Mortality
Drug Interactions
New Drug Approvals: Eravacycline and Omadacycline
Chloramphenicol
Structure and Mechanism of Action
Pharmacology
Administration and Dosage
Absorption and Bioavailability
Drug Distribution
Drug Elimination
Antimicrobial Activity
Gram-Positive Bacteria
Gram-Negative Bacteria
Anaerobic Bacteria
Other Organisms
Clinical Uses
Bacterial Meningitis and Brain Abscess
Salmonella Infections
Other Infections
Mechanism of Resistance
Adverse Reactions
Hematologic Toxicity
Bone Marrow Suppression
Aplastic Anemia
Gray Baby Syndrome
Optic Neuritis and Neurologic Side Effects
Other Reactions
Drug Interactions
Acknowledgment
Key References
References
27 Rifamycins
Short View Summary
Structure and Mechanism of Action
Mechanisms of Resistance
Shared Properties of the Rifamycins
Rifampin
Pharmacokinetics
Adverse Reactions
Antimicrobial Activity
Rifabutin
Pharmacokinetics
Adverse Reactions
Antimicrobial Activity
Rifapentine
Pharmacokinetics
Adverse Effects
Antimicrobial Activity
Rifaximin
Pharmacokinetics
Adverse Effects
Antimicrobial Activity
Immune-Modulating Effects of Rifampin
Rifamycins for the Treatment of Tuberculosis
Rifamycins for Treatment of Latent Tuberculosis Infection
Rifamycins for Nontuberculous Mycobacterial Infections
Mycobacterium leprae
Mycobacterium avium-intracellulare Complex
Mycobacterium kansasii
Other Nontuberculous Mycobacteria
Rifamycins for Nontuberculous Mycobacterial Infections
Staphylococcal Infections
Staphylococcal Biofilms: Foreign-Body Infections and the Role of Rifampin
Vancomycin-Intermediate and Vancomycin-Resistant Staphylococcus aureus and Rifampin
Prosthetic Joint Infections
Osteomyelitis
Central Nervous System Infections
Infections Caused by Other Bacteria
Streptococcus pneumoniae
Enterococci
Legionella
Rhodococcus
Multidrug-Resistant Gram-Negative Bacilli
Brucella
Bartonella
Fungal Infections
Second-Line Indications for Rifamycins
Chemoprophylaxis
Novel and Future Indications for Rifampin
Rifaximin: a Selective Gastrointestinal Rifamycin
Rifalazil
Rifamycins in Development
Key References
References
28 Metronidazole
Short View Summary
History
Mechanism of Action
Spectrum of Activity
Effects on the Human Microbiome
Pharmacology
Adverse Effects, Contraindications, and Precautions
Contraindications
Precautions
Adverse Effects
Mechanisms of Resistance
Clinical Uses
Parasitic Infections
Trichomonas
Dientamoeba
Entamoeba
Giardia
Anaerobic Infections
Clostridioides difficile Infection
Helicobacter pylori Infection
Other Therapeutic Uses
Prophylactic Use
Drug Interactions and Interference With Laboratory Tests
Other Nitroimidazole Antimicrobials
Key References
References
29 Macrolides and Clindamycin
Short View Summary
Erythromycin
Derivation, Chemistry, and Preparations
Mechanisms of Action
Mechanisms of Resistance
Decreased Microbial Entry or Export of Drug
Target Site Alterations
Drug Inactivation
Antimicrobial Activity
Clinical Pharmacology
Adverse Reactions
Drug Interactions
Uses of Erythromycin
Azithromycin and Clarithromycin
Derivation, Chemistry, and Preparations
Mechanisms of Action and Resistance
Antimicrobial Activity
Clinical Pharmacology
Adverse Reactions
Drug Interactions
Uses of Clarithromycin and Azithromycin
Ketolides
Lincomycin and Clindamycin
Derivation, Chemistry, and Preparations
Mechanism of Action
Mechanisms of Resistance
Antimicrobial Activity
Clinical Pharmacology
Adverse Reactions
Drug Interactions
Uses of Clindamycin
Acknowledgments
Key References
References
30 Glycopeptides (Vancomycin and Teicoplanin) and Lipoglycopeptides (Telavancin, Oritavancin, and Dalbavancin)
Short View Summary
Glycopeptides
Vancomycin
Structure and Mechanism of Action
Antimicrobial Activity
Mechanisms of Resistance
Enterococci
Staphylococcus aureus
Heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA)/VISA.
Mechanisms of decreased susceptibility to vancomycin.
Laboratory detection of hVISA strains.
Clinical impact of strains with increased vancomycin minimal inhibitory concentration.
Vancomycin-resistant Staphylococcus aureus.
Coagulase-Negative Staphylococci
Other Gram-Positive Bacteria
Clinical Pharmacodynamics and Pharmacokinetics
Distribution
Excretion
Administration
Dosing in Renal Insufficiency
Adverse Reactions
Drug Interactions
Clinical Uses
Skin and Soft Tissue Infections
Bacteremia and Endocarditis
Meningitis and Ventriculitis
Pneumonia
Osteomyelitis
Pseudomembranous Colitis
Febrile Neutropenia
Prophylaxis
Other Uses
Teicoplanin
Antimicrobial Activity and Resistance
Clinical Pharmacokinetics
Adverse Events
Clinical Uses
Lipoglycopeptides
Telavancin
Structure and Mechanism of Action
Antimicrobial Activity and Resistance
Clinical Pharmacodynamics and Pharmacokinetics
Efficacy of Telavancin in Animal Models
Adverse Reactions
Clinical Uses
Skin and Soft Tissue Infections
Hospital-Acquired Pneumonia
Other Clinical Uses
Dalbavancin
Structure and Mechanism of Action
Antimicrobial Activity and Resistance
Clinical Pharmacodynamics and Pharmacokinetics
Adverse Reactions
Clinical Uses
Oritavancin
Structure and Mechanism of Action
Antimicrobial Activity and Resistance
Clinical Pharmacokinetics and Pharmacodynamics
Adverse Reactions and Drug Interactions
Clinical Uses
Conclusions
Key References
References
31 Daptomycin and Quinupristin-Dalfopristin
Short View Summary
Daptomycin
Mechanism of Action
Antimicrobial Activity
Resistance
Clinical Pharmacokinetics and Pharmacodynamics
Distribution and Elimination
Pharmacodynamics
Drug Dosage and Administration
Adverse Reactions and Drug Interactions
Clinical Uses
Skin and Soft Tissue Infections
Staphylococcus aureus Bacteremia and Right-Sided Endocarditis
Osteoarticular Infections Caused by Staphylococci
Enterococcal Infections
Other Clinical Uses
Streptogramins
Quinupristin-Dalfopristin
Mechanism of Action
Antimicrobial Activity
Resistance
Clinical Pharmacodynamics and Pharmacokinetics
Distribution and Elimination
Administration and Dosing
Adverse Events and Drug Interactions
Clinical Uses
Key References
References
32 Polymyxins (Polymyxin B and Colistin)
Short View Summary
Structure, Source, and Available Preparations
Mechanism of Action
Antimicrobial Activity
Pharmacokinetics
Colistimethate Sodium
Polymyxin B
Pharmacodynamics
Toxicity
Clinical Use
Key References
References
33 Linezolid, Tedizolid, and Other Oxazolidinones
Short View Summary
Chemical Structure
Mechanism of Action
Antimicrobial Activity
General Considerations
Activity Against Gram-Positive Organisms
Activity Against Higher Order Bacteria
Activity Against Mycobacterium spp.
Activity Against Other Organisms
Resistance
Pharmacology
Linezolid
Tedizolid
Clinical Use
Linezolid
Tedizolid
Staphylococcus aureus Including Methicillin-Resistant S. aureus
Linezolid
Tedizolid
Coagulase-Negative Staphylococci
Vancomycin-Resistant Enterococci
Tedizolid
Streptococci Including Streptococcus pneumoniae
Linezolid
Tedizolid
Mycobacterium Including Mycobacterium tuberculosis
Linezolid
Tedizolid
Nocardia spp.
Linezolid
Tedizolid
Untoward Reactions
Hematologic Toxicity
Monoamine Oxidase Inhibition
Adverse Effects Associated With Mitochondrial Toxicity
Neuropathy
Lactic Acidosis
Miscellaneous Untoward Reactions
Linezolid Versus Tedizolid
Other Oxazolidinones
Key References
References
34 Sulfonamides and Trimethoprim; Trimethoprim-Sulfamethoxazole
Short View Summary
Sulfonamides
Structure
Derivation and Nomenclature
Short-Acting or Medium-Acting Sulfonamides
Long-Acting Sulfonamides
Sulfonamides Limited to the Gastrointestinal Tract
Topical Sulfonamides
Mechanisms of Action
Antimicrobial Activity in vitro
Antimicrobial Resistance
Pharmacology
Routes of Administration
Absorption
Distribution
Metabolism and Excretion
Protein Binding and Blood or Tissue Levels
Toxicity and Adverse Reactions
Drug Interactions
Major Clinical Uses
Trimethoprim
Structure and Derivation
Mechanism of Action
Antimicrobial Activity
Resistance to Trimethoprim
Pharmacology
Routes of Administration
Distribution
Metabolism and Excretion
Clinical Use
Trimethoprim-Sulfamethoxazole
Mechanism of Action and Antimicrobial Activity
Trimethoprim-Sulfamethoxazole Resistance
Metabolism and Excretion
Toxicity and Side Effects
Dermatologic Reactions
Hematologic Reactions
Renal and Electrolyte Abnormalities
Gastroenterologic and Hepatic Effects
Neurologic and Psychiatric Effects
Miscellaneous Adverse Effects
Drug Interactions
Trimethoprim Plus Other Antimicrobial Agents
Clinical Uses of Trimethoprim-Sulfamethoxazole
Urinary Tract Infections
Respiratory Tract Infections
Gastrointestinal Infections
Skin, Soft Tissue, and Bone Infections
Sexually Transmitted Diseases
Other Infections
Pneumocystis jiroveci Infections in HIV-Infected Patients
Trimethoprim-Sulfamethoxazole Use in Other Immunocompromised Patients
Trimethoprim Use in Pregnancy
Iclaprim
Key References
References
35 Quinolones
Short View Summary
Chemical Structures
Mechanism of Action
Mechanisms of Acquired Bacterial Resistance
Antimicrobial Activity
Pharmacology
Absorption
Distribution in Tissues
Elimination
Dosage Adjustments in Renal and Hepatic Insufficiency
Interactions With Other Drugs
Clinical Uses
Urinary Tract Infections
Prostatitis
Sexually Transmitted Diseases
Gastrointestinal and Abdominal Infections
Respiratory Tract Infections
Bone and Joint Infections
Skin and Soft Tissue Infections
Other Uses
Problems With Quinolone Resistance During Clinical Use
Adverse Effects
Key References
References
36 Unique Antibacterial Agents
Short View Summary
Multidrug-Resistant Bacteria
Plazomicin (ACHN-490)
Cefiderocol (S-649266)
Meropenem-Vaborbactam (Vabomere)
Fosfomycin (ZTI-01, Contepo): Intravenous
Omadacycline (PTK 0796, Nuzyra)
Eravacycline (TP-434, Xerava)
Lefamulin (BC-3781)
Iclaprim
Overall Conclusions
Acknowledgments
References
37 Urinary Tract Agents
Short View Summary
Nitrofurantoin
Mechanisms of Drug Action and Bacterial Resistance
Spectrum of Activity
Pharmacology
Absorption
Distribution
Excretion
Dosing
Indications
Acute Uncomplicated Cystitis
Acute Pyelonephritis and Complicated Urinary Tract Infections
Prophylaxis for Recurrent Urinary Tract Infections
Adverse Effects
Pulmonary Reactions
Gastrointestinal Reactions
Cutaneous Reactions
Hepatic Reactions
Hematologic Reactions
Peripheral Neuropathy
Systemic Inflammatory Response Syndrome
Drug Interactions
Use in Children and During Pregnancy
Fosfomycin
Mechanism of Action and Antimicrobial Activity
Pharmacology
Dosing
Indications
Acute Uncomplicated Cystitis
Adverse Effects
Use During Pregnancy
Methenamine
Mechanism of Action and Antimicrobial Activity
Pharmacology
Absorption and Distribution
Factors Affecting Formaldehyde Concentrations in Urine
Acidification of Urine During Methenamine Treatment
Dosing
Indications
Adverse Effects
Key References
References
38 Topical Antibacterials
Short View Summary
General Uses of Topical Antibacterials
Skin Disinfection
Prophylaxis of Infection in Clean Wounds
Prophylaxis of Recurrent Skin and Soft Tissue Infections
Prophylaxis of Infection in Operative Wounds
MRSA Decolonization
Universal Decolonization
Targeted Decolonization for Patients Who Screen Positive for Staphylococcus aureus
Topical Skin Antisepsis
Methods to Decrease Bioburden on Skin
Prophylaxis of Vascular Catheter–Related Infections
Prophylaxis of Peritoneal Dialysis Catheter Infections
Prophylaxis of Hemodialysis Catheter Infections
Prophylaxis of Health Care–Associated Infections
Prophylaxis of Infection in Burn Wounds
Treatment of Pyoderma
Treatment of Erythrasma and Rosacea
Treatment of Acne Vulgaris
Elimination of Staphylococcus aureus Nasal Carriage
Specific Topical Antibacterials
Bacitracin
Mechanism of Effects
In Vitro Spectrum of Activity
Clinical Uses
Adverse Effects
Neomycin
Mechanism of Action
In Vitro Spectrum of Activity
Clinical Uses
Adverse Effects
Polymyxin B
Mechanism of Action
In Vitro Spectrum of Activity
Clinical Uses
Adverse Effects
Mupirocin
Structure and Mechanism of Action
In Vitro Spectrum of Activity
Pharmacokinetics
Clinical Uses
Adverse Effects
Key References
References
39 Antimycobacterial Agents
Short View Summary
First-Line Antituberculous Drugs
Isoniazid
Derivation and Structure
Mechanism of Action
Antimicrobial Activity and Resistance
Pharmacology
Adverse Reactions
Hepatitis.
Neurotoxicity.
Hypersensitivity reactions.
Miscellaneous adverse reactions.
Overdose
Significant Drug Interactions
Usage
Availability and Dosage
Rifampin (see also Chapter 27)
Derivation and Structure
Mechanism of Action
Antimicrobial Activity and Resistance
Pharmacology
Adverse Reactions
Hepatitis.
Effects on immune parameters.
Hypersensitivity reactions.
Miscellaneous adverse reactions.
Significant Drug Interactions
Usage
Availability and Dosage
Pyrazinamide
Derivation and Structure
Mechanism of Action
Antimicrobial Activity and Resistance
Pharmacology
Adverse Reactions
Significant Drug Interactions
Usage
Availability and Dosage
Ethambutol
Derivation and Structure
Mechanism of Action
Antimicrobial Activity and Resistance
Pharmacology
Adverse Reactions
Significant Drug Interactions
Usage
Availability and Dosage
Streptomycin
Derivation, Structure, and Pharmacology
Antimicrobial Activity and Resistance
Adverse Reactions
Significant Drug Interactions
Usage
Availability and Dosage
Alternatives to Rifampin
Rifabutin
Derivation and Pharmacology
Adverse Reactions
Significant Drug Interactions
Usage
Rifapentine
Derivation and Pharmacology
Adverse Drug Reactions
Significant Drug Interactions
Usage
Availability and Dosage
Second-Line Antituberculous Drugs
Quinolones (see Chapter 35)
Mechanism of Action
Antimicrobial Activity and Resistance
Usage
Adverse Reactions
Significant Drug Reactions
Linezolid (see Chapter 33)
Capreomycin, Amikacin, and Kanamycin
Capreomycin
Antimicrobial Activity and Resistance
Adverse Reactions
Significant Drug Interactions
Usage
Availability and Dosage
Amikacin
Antimicrobial Activity and Resistance
Adverse Reactions
Usage
Kanamycin
Availability and Dosage
Para-Aminosalicylic Acid
Derivation, Structure, and Pharmacology
Adverse Reactions
Usage
Availability and Dosage
Cycloserine
Derivation and Mechanism of Action
Pharmacology
Adverse Reactions
Usage
Availability and Dosage
Ethionamide
Derivation, Mechanism of Action, and Resistance
Pharmacology
Adverse Reactions
Usage
Availability and Dosage
β-Lactams
Amithiozone
New Drugs for Tuberculosis
World Health Organization Antituberculosis Drug Classification for Drug-Resistant Tuberculosis
Therapeutic Drug Monitoring
Coadministration of Antituberculosis Therapy and Human Immunodeficiency Virus Medications
Major Drugs for Treatment of Nontuberculous Mycobacterial Infections (see Chapters 251 and 252)
Macrolides (see Chapter 29)
Antimicrobial Activity and Resistance
Pharmacology
Adverse Reactions
Significant Drug Interactions
Dosage
Rifampin
Antimicrobial Activity
Pharmacology, Adverse Events, and Significant Drug Interactions
Usage
Rifabutin
Antimicrobial Activity
Pharmacology, Adverse Events, and Significant Drug Interactions
Usage
Aminoglycosides
Ethambutol
Less Frequently Used Miscellaneous Antimicrobial Agents for Treatment of Nontuberculous Mycobacteria
Isoniazid
Tetracyclines
Sulfonamides
Quinolones
Linezolid
β-Lactams
Clofazimine
Susceptibility Tests
Drugs for Treatment of Hansen Disease (Leprosy) (see Chapter 250)
Background
Dapsone
Derivation and Structure
Mechanism of Action
Antimicrobial Activity
Pharmacology
Adverse Reactions
Usage
Availability and Dosage
Rifampin
Mechanism of Action and Resistance
Usage
Clofazimine (Lamprene)
Derivation and Structure
Mechanism of Action and Antimicrobial Activity
Pharmacology
Adverse Reactions
Usage
Availability and Dosage
Additional or Second-Line Drugs
Thiacetazone (Amithiozone)
Ethionamide and Protionamide
Other Substituted Rifamycins
Other Sulfones
Acedapsone
Sulfoxone
Newer Agents
Chemotherapy-Associated Reactions in Leprosy
Key References
References
40A Antifungal Agents
General Features
Mechanism of Action
Spectrum of Activity and Mechanisms of Resistance
Available Formulations
Amphotericin B Deoxycholate
Formulation
Pharmacology
Toxicity
Nephrotoxicity
Other Chronic Toxicity
Acute Reactions
Administration
Dosage
Lipid-Associated Formulations of Amphotericin B
Pharmacology and Toxicity
Amphotericin B Lipid Complex
Liposomal Amphotericin B
Comparison of Amphotericin B Deoxycholate and the Lipid-Associated Formulations of Amphotericin B
Other Routes for Amphotericin B
Key References
References
40B Antifungal Drugs
Short View Summary
Mechanisms of Triazole Resistance
Fluconazole (Diflucan)
Formulations and Pharmacology
Drug Interactions
Side Effects
Therapeutic Drug Monitoring
Indications
Candidiasis
Cryptococcosis
Other Mycoses
Prophylaxis in Neutropenic Patients
Prophylaxis in Acquired Immunodeficiency Syndrome
Prophylaxis in Preterm Neonates
Itraconazole (Sporanox) and Enhanced Bioavailability Suba-Itraconazole (Tolsura/Lozanoc)
Formulations and Pharmacology
Drug Interactions
Side Effects
Therapeutic Drug Monitoring
Clinical Use
Voriconazole (Vfend)
Formulations and Pharmacology
Drug Interactions
Side Effects
Therapeutic Drug Monitoring
Clinical Use
Aspergillosis
Febrile Neutropenia
Other Mycoses
Posaconazole (Noxafil)
Formulations and Pharmacology
Drug Interactions
Side Effects
Therapeutic Drug Monitoring
Clinical Use
Prophylaxis in High-Risk Patients
Other Mycoses
Isavuconazole (Cresemba)
Formulations and Pharmacology
Drug Interactions
Side Effects
Therapeutic Drug Monitoring
Aspergillosis and Mucormycosis
Other Use
Investigational Agents
Acknowledgments
Key References
References
40C Antifungal Drugs
Short View Summary
Structure, Mechanism of Action, and Spectrum of Activity
Pharmacology
Susceptibility Testing in vitro
Echinocandin Resistance
Clinical Indications
Candidiasis
Aspergillosis
Empirical Treatment of Febrile Neutropenia and Antifungal Prophylaxis
New Agents: Rezafungin and Ibrexafungerp
Key References
References
40D Antifungal Drugs
Short View Summary
Pharmacology
Antimicrobial Activity
Resistance
Pharmacokinetics
Pharmacodynamics
Dosing, Administration, and Monitoring
Therapeutic Drug Monitoring
Toxicity
Gastrointestinal
Myelosuppression
Hepatotoxicity
Key References
References
41 Antimalarial Drugs
Short View Summary
Artemisinin Derivatives
Structures of Artemisinin Compounds
Pharmacokinetics and Dynamics
Clinical Use
Severe Malaria
Resistance
Toxicity
Artemisinin Partner Drugs
Lumefantrine
Pharmacokinetics
Clinical Use
Toxicity
Piperaquine
Pharmacokinetics
Clinical Use
Resistance
Toxicity
Pyronaridine
Pharmacokinetics
Clinical Use
Toxicity
Amodiaquine
Pharmacokinetics
Clinical Use
Toxicity
Mefloquine
Pharmacokinetics
Clinical Use
Resistance
Toxicity
Chloroquine
Pharmacokinetics
Clinical Use
Resistance
Toxicity
Quinine and Quinidine
Pharmacokinetics
Clinical Use
Quinine Resistance
Quinine for Treatment of Babesiosis
Toxicity
8-Aminoquinolines
Primaquine
Pharmacokinetics
Clinical Use
Radical Cure
Reduction of Transmission
Chemoprophylaxis
Toxicity
Tafenoquine
Pharmacokinetics
Clinical Use
Toxicity
Atovaquone
Pharmacokinetics
Clinical Use
Resistance
Toxicity
Folate Antagonists
Dihydrofolate Reductase Inhibitors
Proguanil (Chloroguanide)
Pharmacokinetics
Pyrimethamine
Pharmacokinetics
Toxicity
Trimethoprim
Dihydropteroate Synthetase Inhibitors
Sulfonamides
Sulfadiazine and Sulfamethoxazole
Sulfadoxine
Pharmacokinetics
Toxicity
Sulfones
Antibiotics With Antimalarial Activity
Doxycycline and Tetracycline
Macrolides
Azithromycin
Clindamycin
Key References
References
42 Drugs for Protozoal Infections Other Than Malaria
Short View Summary
Drugs for Leishmaniasis and Trypanosomiasis
Amphotericin B
Antimonials
Triazoles
Miltefosine
Paromomycin
Pentamidine
Benznidazole
Fexinidazole
Eflornithine
Melarsoprol
Nifurtimox
Suramin
Nitazoxanide
Diloxanide
Nitroimidazoles
Spiramycin
Atovaquone
Other Drugs Rarely Used to Treat Intestinal Protozoal Infections
Key References
References
43 Drugs for Helminths
Short View Summary
Benzimidazoles
Albendazole
Mebendazole
Thiabendazole
Triclabendazole
Macrocyclic Lactones
Ivermectin
Moxidectin
Diethylcarbamazine
Piperazine
Doxycycline
Pyrantel and Oxantel Pamoate
Levamisole
Tribendimidine
Praziquantel
Oxamniquine
Metrifonate
Niclosamide
Nitazoxanide
Bithionol
Key References
References
44 Antiviral Agents
Mechanisms of Action of Antiviral Agents
Inhibition of Viral Nucleic Acid Synthesis
Integrase Strand Inhibitors
CAP-Dependent Endonuclease Inhibitor
RNA Antisense Nucleotides
Viral Entry Inhibition
Protease Inhibition
Inhibition of Virus Uncoating
Inhibition of Virus Release
Modifiers of Host Defenses Against Viruses
Interferons
Innate Immunity Stimulators
Host Sialidases
Determination of Sensitivity of Viruses to Antiviral Agents
Quantitation of Virus (Virus Load)
Resistance to Antiviral Agents
Combinations of Antiviral Agents
Pharmacodynamics
References
45 Antiviral Drugs for Influenza and Other Respiratory Virus Infections
Short View Summary
Amantadine and Rimantadine
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Amantadine
Rimantadine
Interactions
Toxicity
Clinical Studies
Influenza A
Other Viruses
DAS181 (Fludase)
Favipiravir (T-705)
Laninamivir Octanoate
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Toxicity
Clinical Studies
Oseltamivir
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Peramivir
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Ribavirin
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Toxicity
Interactions
Clinical Studies
Respiratory Syncytial Virus
Other Respiratory Viruses
RSV604
Zanamivir
Spectrum
Resistance
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Polymeric Zanamivir Conjugates
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Interactions and Toxicity
Clinical Studies
Baloxavir Marboxil
Key References
References
46 Antivirals Against Herpesviruses
Acyclovir and Valacyclovir
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Herpes Simplex Virus
Varicella-Zoster Virus Infections
Cytomegalovirus
Other Viruses
Brivudin
Cidofovir
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
CMX-001 (Brincidofovir)
Docosanol
Famciclovir and Penciclovir
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Fomivirsen
Foscarnet
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Ganciclovir and Valganciclovir
Spectrum
Mechanism of Action
Resistance
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Idoxuridine
Letermovir (AIC246)
Trifluridine
Vidarabine
Maribavir
Helicase-Primase Inhibitors (Amenamevir, Pritelivir)
Amenamevir (ASP2151)
Pritelivir (AIC316)
Tenofovir
Key References
References
47 Antiviral Drugs Against Hepatitis Viruses
Short View Summary
Hepatitis B
Overview
Adefovir
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Entecavir
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Interferons
Lamivudine
Spectrum and Mechanism of Action
Resistance
Toxicity
Clinical Studies
Telbivudine
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Tenofovir Disoproxil Fumarate
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Toxicity
Clinical Studies in Hepatitis B Virus Infection
Tenofovir Alafenamide
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Drug Interactions
Toxicity
Clinical Studies
Other Agents of Potential Interest
Emtricitabine
Clevudine
The Future
Hepatitis C
Overview
Interferons
Ribavirin
Boceprevir
Spectrum and Mechanism of Action
Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Telaprevir
Spectrum and Mechanism of Action
Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Simeprevir
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Sofosbuvir
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Ledipasvir/Sofosbuvir (Harvoni)
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Drug Interaction
Toxicity
Clinical Studies
Paritaprevir/Ritonavir/Ombitasvir Plus Dasabuvir (Viekira Pak)
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Paritaprevir/Ritonavir/Ombitasvir (Technivie)
Elbasvir/Grazoprevir (Zepatier)
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Drug Interactions
Toxicity
Clinical Studies
Daclatasvir (Daklinza)
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Drug Interactions
Toxicity
Clinical Studies
Velpatasvir/Sofosbuvir (Epclusa)
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Drug Interactions
Toxicity
Clinical Studies
Glecaprevir/Pibrentasvir (Mavyret)
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Drug Interactions
Toxicity
Clinical Studies
Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi)
Spectrum and Mechanism of Action
Resistance
Pharmacology/Pharmacokinetics
Drug Interactions
Toxicity
Clinical Studies
State of the Art
Key References
References
48 Miscellaneous Antiviral Agents (Interferons, Tecovirimat, Imiquimod, Pocapavir, Pleconaril)
Short View Summary
Interferons
Classification
Mechanisms of Action
Pharmacokinetics
Interactions
Toxicity
Clinical Studies
Herpesviruses
Human Immunodeficiency Virus
Papillomavirus
Respiratory Viruses
Enteroviruses
Tecovirimat
Imiquimod and Resiquimod
Pleconaril
Pocapavir
Key References
References
49 Immunomodulators
Short View Summary
Colony-Stimulating Factors
Granulocyte Colony-Stimulating Factor
Adverse Effects of Granulocyte Colony-Stimulating Factor
Granulocyte Transfusions
Granulocyte-Macrophage Colony-Stimulating Factor
Adverse Effects of Granulocyte-Macrophage Colony-Stimulating Factor
Macrophage Colony-Stimulating Factor
Interferons
Interferon-α
Interferon-β
Interferon-γ
Interleukins
Interleukin-1
Interleukin-2
Interleukin-7
Interleukin-10
Interleukin-11
Interleukin-12
Thymic Hormones
Immunoglobulins
Monoclonal Antibodies
Glucocorticosteroids
Synthetic Compounds With Immunomodulatory Activity
Cell-Based Immunomodulatory Therapy
Immunomodulatory Therapy and Infectious Risks
Key References
References
50 Hyperbaric Oxygen
Short View Summary
Physiologic Effects in Experimental Models
Modulation of Inflammation and Immune Function
Angiogenesis and Improved Wound Healing
Antibacterial Properties
Activity of Antimicrobial Agents
Administration
Indications
Diabetic Foot Ulcers
Necrotizing Soft Tissue Infections
Clostridial Myonecrosis (Gas Gangrene)
Refractory Osteomyelitis
Bacterial Intracranial Abscess
Mucormycosis
Side Effects and Complications
Patient Selection and Evaluation
Cost
Controversy
Certification in Hyperbaric Medicine
Conclusions
Key References
References
51 Antimicrobial Stewardship
Short View Summary
Antimicrobial Stewardship
Philosophy and Sociology of Antimicrobial Use
Antimicrobial Stewardship Strategies
Educational Strategies
Antimicrobial Formulary Restriction Strategies
Preauthorization Strategies
Postprescription Review With Feedback
Computer-Assisted Antimicrobial Stewardship
Measuring Outcomes From Antimicrobial Stewardship Programs
Clinical Outcomes
Economic Outcomes
Microbiologic Outcomes
Antimicrobial Stewardship Program Structure and Implementation
Acute-Care Hospitals and Long-Term Care Facilities
Outpatient and Ambulatory Care
The Future
Acknowledgment
Key References
References
52 Designing and Interpreting Clinical Studies in Infectious Diseases
Lexicon of Terms in Clinical Study Design and Analysis
Types of Studies
Controls in Clinical Studies
Trial Hypotheses
Types of Error in Clinical Trials
Methods to Control Bias in Clinical Trials
Types of Nonrandomized Studies
Methods to Attempt to Control Selection Bias in Nonrandomized Studies
Outcomes of Clinical Studies
Analysis Populations
Analysis of Study Results
Overview
History
Defining Terms
Choosing a Research Question and Defining Goals of a Study
Types of Analytical Study Designs
Comparison With a Control Group
Types of Hypotheses
Design of Noninferiority Trials
Selection of Study Participants
Minimizing Error in Studies
Baseline Comparability Between Study Groups
Outcome Assessments
Analysis of Study Results
Analysis of Populations
Examining Baseline Comparability
Calculating Differences Between Groups
Examining the Evidence: P Values and Confidence Intervals
Measurement of Harms
Subgroup Analyses
Examining the Conclusions
Key References
References
53 Outpatient Parenteral Antimicrobial Therapy
The History and Growth of OPAT
Patient Selection for OPAT
OPAT in People Who Inject Drugs
Alternate Options for OPAT
Use of Oral Antibiotic Therapy
Use of Long-Acting Parenteral Agents
Programmatic Requirements
Infectious Diseases Provider
OPAT Pharmacist
Infusion Nurse Support
Antimicrobial Stewardship
System for Data Management and Communication
Antimicrobial Considerations
Drug Characteristics and Regimens
Methods of Infusion and Drug Delivery
Laboratory Monitoring of Antibiotic Therapy
OPAT Program Outcome Measurement
Readmissions
Complications of Vascular Access Devices
Financial Analysis of OPAT Programs
Patient Satisfaction
Future of OPAT
Key References
References
54 Tables of Antiinfective Agent Pharmacology
Dosage Guidelines
Dosage Adjustment for Renal Impairment
Dosage Adjustment for Hepatic Impairment
Dosage Adjustment for Body Size (Obese and Underweight)
Drug-Drug Interactions
Suggested Readings
II Major Clinical Syndromes
A Fever
55 Temperature Regulation and the Pathogenesis of Fever
Short View Summary
Terminology
Clinical Thermometry
Anatomic Variability
Physiologic Variables
“Normal Body Temperature”
Thermoregulation
The Generation of Fever
Acute-Phase Response
Biologic Value of Fever
Biologic Value of Fever: the Case of Sepsis
Biologic Value of Hypothermia
Antipyretic Therapy: General Considerations
Antipyretic Therapy: the Case of Sepsis
Antipyretic Therapy: Pharmacologic Agents
Antipyretic Therapy: Physical Methods of Antipyresis
Acknowledgment
Key References
References
56 Fever of Unknown Origin
Short View Summary
Terminology and Definitions
Classic Fever of Unknown Origin
Infants and Children
Elderly Persons
Returned Travelers
Nosocomial (Health Care–Associated) Fever of Unknown Origin
Postoperative Patients
Intensive Care Unit Patients
Stroke Patients
Neutropenic (Immune-Deficient) Fever of Unknown Origin
HIV-Related Fever of Unknown Origin
Diagnosis
History
Verification of Fever and Fever Pattern
Physical Examination
Laboratory Investigations
Imaging Studies
Invasive Diagnostic Procedures
Molecular Genetic Testing
Therapy
Therapeutic Trials
Management
Prognosis
Acknowledgement
Key References
References
57 The Acutely Ill Patient With Fever and Rash
Short View Summary
Approach to the Patient
Pathogenesis of Rash
Differential Diagnosis in Rash
Characteristics of the Lesion
Maculopapular Rash
Nodular Lesions
Diffuse Erythema
Vesiculobullous Eruptions
Petechial and Purpuric Eruptions
Enanthems
Neutrophilic Dermatoses, Including Sweet Syndrome
Pathogens or Infectious Conditions Strongly Associated With Rash
Sepsis
Neisseria meningitidis Infection
Pseudomonas Infection
Bacterial Endocarditis
Infections Due to Staphylococcus aureus and Streptococcus pyogenes
Staphylococcal Scalded Skin Syndrome
Staphylococcal Toxic Shock Syndrome
Streptococcal Infections
Rickettsial Infections
Ehrlichia and Anaplasma Species
Borrelia burgdorferi Infection
Syphilis
Candidiasis
Measles
New and Emerging Infectious Diseases
Dengue, Chikungunya, and Zika Viruses
Viral Hemorrhagic Fever
Bacterial Diseases Due to Bartonella Species
Orthopoxviruses
Skin Lesions in Immunocompromised Patients
Key References
References
B Upper Respiratory Tract Infections
58 The Common Cold
Short View Summary
Etiology
Epidemiology
Transmission
Predisposing Factors
Immunity
Clinical Manifestations
Pathogenesis
Differential Diagnosis
Complications
Therapy
Symptomatic Therapy
Homeopathic Remedies
Antiviral Therapy
Hand Hygiene
Key References
References
59 Pharyngitis
Short View Summary
Definition
Etiology
Epidemiology
Pathogenesis
Microbiology
Group A Streptococcus
Non–group A Streptococcus
Fusobacterium necrophorum
Arcanobacterium haemolyticum
Corynebacterium diphtheriae
Neisseria gonorrhoeae
Atypical Bacteria
Epstein-Barr Virus
Human Immunodeficiency Virus
Enteroviruses
Adenovirus
Herpes Simplex Virus
Diagnosis
Culture for Group A Streptococci
Rapid Antigen Detection Test
Other Diagnostic Tests
Therapy
Complications
Key References
References
60 Acute Laryngitis
Short View Summary
Definition
Epidemiology
Microbiology
Diagnosis and Therapy
Complications
Key References
References
61 Otitis Externa, Otitis Media, and Mastoiditis
Short View Summary
Otitis Externa
Pathogenesis
Clinical Manifestations and Management
Otitis Media
Epidemiology
Pathogenesis
Microbiology
Bacteria.
Viruses
Mycoplasma, Chlamydia, and Unusual Organisms
Immunology
Diagnosis and Clinical Course
Management
Acute Otitis Media
Systemic and Topical Treatment of Otalgia
Antibiotic Therapy Versus Observation
Selection of Antimicrobial Agents
Treatment of Otitis Media With Effusion
Surgical Management
Prevention of Acute Otitis Media
Chemoprophylaxis
Pneumococcal Vaccines
Respiratory Virus Vaccines
Additional Complications of Acute Otitis Media
Mastoiditis
Clinical Manifestations
Diagnosis
Management
Key References
References
62 Sinusitis
Short View Summary
Anatomy and Physiology of the Paranasal Sinuses
Pathogenesis
Microbiology
Chronic Sinusitis
Epidemiology
Clinical Manifestations
Diagnosis of Sinusitis
Clinical Diagnosis
Imaging
Therapy
Antimicrobial
Adjunctive Treatment
Corticosteroids
Antihistamines/Decongestants
Saline
Sinus Surgery
Complications
Prevention
Key References
References
63 Epiglottitis
Short View Summary
Epidemiology and Etiology
Clinical Manifestations
Diagnosis
Differential Diagnosis
Therapy
Initial Management
Antibiotic Therapy
Prevention
Key References
References
64 Infections of the Oral Cavity, Neck, and Head
Short View Summary
Microbiologic Considerations
Unique Niches of the Indigenous Oral Microbiota
Microbial Specificity in Odontogenic Infections
Pathogenetic Mechanisms
Mucosal Immunity of the Oral Cavity
Anatomic Considerations
Clinical Manifestations and Management
Orofacial Odontogenic Infections
Dentoalveolar Infections
Gingivitis and Periodontal Infections
Gingivitis
Periodontitis
Periodontal Abscess
Pericoronitis
Deep Fascial Space Infections
Space Infections Around the Face
Masticator spaces.
Buccal, canine, and parotid spaces.
Suprahyoid Space Infections
Submandibular and sublingual spaces.
Ludwig angina.
Lateral pharyngeal space.
Infrahyoid Space Infections
Retropharygeal and danger spaces.
Pretracheal space.
Complications of Odontogenic Infections
Suppurative Jugular Thrombophlebitis (Lemierre Syndrome) and Carotid Artery Erosion
Septic Cavernous Sinus Thrombosis
Maxillary Sinusitis
Osteomyelitis of the Jaws
Association With Cardiovascular Risk
Orofacial Nonodontogenic Infections
Infections of the Oral Mucosa
Noma (Gangrenous Stomatitis)
Aphthous Stomatitis
Mucositis and Stomatitis in the Severely Immunocompromised Patient
Infections of the Salivary Gland
Suppurative Parotitis
Chronic Bacterial Parotitis
Viral Parotitis
Miscellaneous Infections of the Neck and Head
Suppurative Cervical Adenitis
Infected Embryologic Cysts
Suppurative Thyroiditis
Infections from Bites, Irradiation, and Surgical Wounds
Human and Animal Bites
Irradiation and Postsurgical Wounds
Diagnostic Approaches
Microbiologic Investigation
Imaging Techniques for the Localization of Infection
Therapeutic Considerations
Dental Caries and Periodontitis
Suppurative Soft Tissue Infections
Osteomyelitis
Key References
References
C Pleuropulmonary and Bronchial Infections
65 Acute Bronchitis
Short View Summary
Microbial Etiology
Pathogenesis
Clinical Manifestations
Diagnosis
Therapy
Prevention
Key References
References
66 Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Short View Summary
Epidemiology
Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Clinical Presentation
Diagnosis
Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Radiology
Pathophysiology
Mucosal Inflammation
Microbes in Stable Chronic Obstructive Pulmonary Disease
Microbes in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Treatment
Nonantimicrobial Treatment of Steady-State Chronic Obstructive Pulmonary Disease
Nonantimicrobial Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Antibiotic Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Rationale for Antibiotics
Whom to Treat
Choice of Antibiotic
Duration of Antibiotic Treatment
Treatment of Viral Infection
Preventions of Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Antibiotic Prophylaxis in Steady-State Chronic Obstructive Pulmonary Disease
Vaccination
Key References
References
67 Acute Pneumonia
Short View Summary
Host Defenses and Pathogenesis
Pulmonary Defense Systems
Impairment of Pulmonary Defenses
Clinical Evaluation
History
Physical Examination
Diagnostic Testing
Sputum Examination and Examination of Other Respiratory Tract Samples
Fiberoptic Bronchoscopy
Other Techniques
Lung Biopsy
Examination of Pleural Effusions
Blood Culture, Serologic Studies, and Urine Studies, Including Antigen Detection
Radiologic Examination
Pneumonia Syndromes
Acute Community-Acquired Pneumonia
Community-Acquired Pneumonia in the Older Adult
Severe Community-Acquired Pneumonia
Health Care–Associated Pneumonia
“Atypical” Pneumonia Pathogens
Pneumonia in the Setting of Aspiration
Eosinophilic Pneumonias
Hospital-Acquired Pneumonia
Pneumonia in the Immunosuppressed Host
Management and Therapy of Pneumonia
Antimicrobial Therapy
Timing of Antibiotics
Duration of Treatment and Use of Clinical Practice Guidelines
Adjunctive Therapy
Prevention of Pneumonia
Key References
References
68 Pleural Effusion and Empyema
Short View Summary
Physiology and Staging
Noninfectious Effusion and Empyema
Outcomes of Effusion and Empyema
Microbiology
Tuberculosis
Other Bacteria
Viruses
Mycobacteria Other Than Tuberculosis
Fungi
Parasites
Nematodes
Cestodes
Trematodes
Other Parasites
Diagnosis
Fluid Analysis
Treatment
Key References
References
69 Bacterial Lung Abscess
Short View Summary
Definition
Pathophysiology
Epidemiology
Clinical Presentation
Microbiology
Diagnosis
Therapy
Duration of Therapy
Surgical Intervention
Response to Therapy and Prognosis
Prevention
Key References
References
70 Chronic Pneumonia
Short View Summary
Causes
Epidemiology
Age, Gender, and Race
Occupation and Hobbies
Residence and Travel
Contacts, Habits, and Drugs
Underlying Disease
Clinical Features
Symptoms
Signs
Diagnostic Procedures
Initial Laboratory Studies
Additional Studies
Chest Radiographic Studies
Patients With Radiographic Evidence of Localized Infiltrates or Cavitation
Invasive Procedures
Patients With Radiographic Evidence of Diffuse Pulmonary Infiltration and Fibrosis
Therapy
Antimicrobial Agents
Corticosteroids
Bronchoscopy and Surgery
Key References
References
71 Cystic Fibrosis
Short View Summary
Clinical Disease
Pathogenesis of Cystic Fibrosis–Related Lung Disease
The Cystic Fibrosis Microbiome
Major Cystic Fibrosis Pathogens
Staphylococcus aureus
Methicillin-Resistant Staphylococcus aureus
Pseudomonas aeruginosa
Burkholderia cepacia Complex
Other Bacteria
Nontuberculous Mycobacteria
Respiratory Viruses
Fungal Disease
Treatment (Table 71.1)
Antimicrobial Treatment
Azithromycin
Inhaled Antibiotics
Cystic Fibrosis–Specific Antibiotic Treatment Approaches
Non–Antibacterial-Based Treatments
Restoring CFTR Function
Infection Control
Lung Transplantation
Future Directions
Key References
References
D Urinary Tract Infections
72 Urinary Tract Infections
Short View Summary
Terminology
Pathologic Characteristics
Acute Pyelonephritis
Chronic Pyelonephritis (Chronic Interstitial Nephritis)
Papillary Necrosis Caused by Infection
Pathogenesis of Urinary Tract Infection
Ascending Route
Hematogenous Route
Urovirulence in Bacteria
Adhesins
Fimbriae
P Fimbriae
Type I Fimbriae
Other Adhesins
Expression and Selection of Virulence Factors
Other Virulence Factors of Uropathogenic E. coli
Host Factors in Urinary Tract Infections
Host Defense of the Urinary Tract
Innate Immunity
Urine and Bladder Defenses
Adherence and Colonization
Humoral and Cellular Immunity
Genetic Factors
Structural Abnormalities
Epidemiology and Natural History of Urinary Tract Infection77
Infecting Organisms
Asymptomatic Bacteriuria Versus Symptomatic Infection
Urinary Tract Infection in Children
Urinary Tract Infection in Adults
Urinary Tract Infection in the Elderly
Urinary Tract Infection in Other Conditions
Infection in the Obstructed Kidney After Urologic Treatment of Hydronephrosis
Infections in Polycystic Kidneys
Clinical Manifestations
Symptoms
Alterations in Renal Function
Diagnosis
Presumptive Diagnosis of Urinary Tract Infection
Diagnosis of Urinary Tract Infection by Culture
General Considerations
Urinary Tract Infection With Low Numbers of Organisms
Localization of Site of Infection
Management of Urinary Tract Infection
General Considerations
Nonantimicrobial Therapy
Prevention of Urinary Tract Infection
Principles of Antimicrobial Therapy
Serum, Tissue, and Urine Concentrations of Antimicrobial Agents
Response to Therapy
Bacteriologic Cure
Bacteriologic Persistence
Bacteriologic Relapse
Reinfection
Considerations in Choice of Therapy
Classification and Antimicrobial Therapy for Different Groups
Infection in Children
Acute Uncomplicated Pyelonephritis in Women
Oral Therapy
Parenteral Therapy
Uncomplicated Cystitis in Women
Complicated Urinary Tract Infection, Including Infection in Men
Asymptomatic Bacteriuria
Relapsing Urinary Tract Infection
Reinfection of the Urinary Tract and Antimicrobial Prophylaxis
Fungal Infections
Urinary Tract Infection in Pregnancy
Physiologic Alterations in the Urinary Tract
Epidemiology
Management of Bacteriuria of Pregnancy
Perinephric Abscess and Intrarenal Abscess
Perinephric Abscess
Intrarenal Abscess
Diagnosis and Therapy
Imaging Studies
Surgical Management
Summary of Treatment Approaches
Key References
References
E Sepsis
73 Sepsis and Septic Shock
Short View Summary
Definition
Clinical Signs and Symptoms
Source of Sepsis
Organ Failure in Sepsis
Acute Lung Injury
Cardiovascular Dysfunction
Renal Dysfunction
Dysfunction of Brain, Peripheral Nerves, and Muscles
Coagulopathy and Disseminated Intravascular Coagulation
Gastrointestinal Tract and Hepatic Injury
Epidemiology
Incidence
Mortality
Trends in Time: Incidence and Mortality
Risk Factors
Microbiology
Main Causative Agents
Virulence Factors of Bacteria Causing Sepsis
Antimicrobial Resistance Trends in the Setting of Sepsis
Pathogenesis
Hyperinflammation
Instigation of Inflammation
Activation of the Complement System
Activation of Coagulation and Vascular Endothelium
Interaction Between Complement and Coagulation Systems
Endothelial Dysfunction
Neutrophil Extracellular Traps
Platelets
Antiinflammatory Mechanisms and Immunosuppression
Suppression of Innate Immune Cell Functions
Suppression of Adaptive Immune Cell Functions
Diagnosis
Hematologic and Biochemical Evaluation
Pathogen Detection
Diagnostic Imaging
Host Response Biomarkers
Therapy
Surviving Sepsis Campaign Guidelines
Empirical Antibiotic Therapy
Immunomodulation
Therapeutics That Seek to Inhibit Hyperinflammation
Therapeutics That Seek to Stimulate the Immune System
Mesenchymal Stem Cells
Prognosis
Future Perspectives
Key References
References
F Intraabdominal Infections
74 Peritonitis and Intraperitoneal Abscesses
Short View Summary
Anatomy and Physiology
Peritonitis
Primary Peritonitis
Etiology
Bacteriologic Characteristics
Pathogenesis
Clinical Manifestations
Laboratory Findings
Diagnosis
Prognosis
Therapy
Prevention
Secondary and Tertiary Peritonitis
Etiology
Microbiologic Characteristics
Pathogenesis
Pathophysiologic Responses
Local Response
Systemic Response
Gastrointestinal.
Cardiovascular.
Respiratory.
Renal.
Metabolic.
Clinical Manifestations
Symptoms
Physical Findings
Diagnostic Studies
Prognosis
Therapy
Antimicrobial Therapy
Chloramphenicol.
Clindamycin.
Metronidazole.
Tetracyclines.
Cephalosporins.
Penicillins.
Carbapenems and aztreonam.
Aminoglycosides.
Fluoroquinolones.
Tigecycline.
Eravacycline.
Pharmacodynamic Considerations
Duration of antimicrobial therapy.
Hyperbaric Oxygen
Gastrointestinal Drainage
Water and Electrolyte Administration
Blood and Plasma Transfusion
Respiratory Support
Operative Approach
Prevention
Peritonitis During Peritoneal Dialysis
Long-Term Peritoneal Dialysis
Source of Infection and Risk Factors
Microbiology
Diagnosis
Treatment and Prognosis
Catheter Removal and Prevention
Acute Peritoneal Dialysis
Intraperitoneal Abscesses
Etiology
Bacteriologic Findings
Pathogenesis
Clinical Manifestations
Diagnosis
Prognosis
Therapy
Key References
References
75 Infections of the Liver and Biliary System (Liver Abscess, Cholangitis, Cholecystitis)
Short View Summary
Liver Abscess
Epidemiology/Etiology
Amebic Liver Abscess
Pyogenic Liver Abscess
Pathogenesis and Pathophysiology
Amebic Liver Abscess
Pyogenic Liver Abscess
Microbiology
Amebic Liver Abscess
Pyogenic Liver Abscess
Epidemic Klebsiella pneumoniae Pyogenic Liver Abscess
Clinical Manifestations
Amebic Liver Abscess
Pyogenic Liver Abscess
Diagnosis
Therapy
Amebic Liver Abscess
Pyogenic Liver Abscess
Infection of the Biliary System
Pathogenesis
Cholecystitis
Acalculous Cholecystitis
Cholangitis
Clinical Manifestations
Diagnosis
Imaging Studies
Microbiology
AIDS Cholangiopathy (AIDS-Related Sclerosing Cholangitis)
Therapy
Acute Cholecystitis
Acute Cholangitis
Key References
References
76 Pancreatic Infection
Short View Summary
Infectious Causes of Acute Pancreatitis
Pancreatitis and Human Immunodeficiency Virus Infection
Infection Complicating Acute Pancreatitis
Background
Significance of Infection in Acute Pancreatitis
Defining Pancreatic Infections
Diagnosis of Pancreatic Infection
Microbiology of Pancreatic Infection
Management of Pancreatic Infection
Prevention of Pancreatic Infection
Early Enteral Feeding
Selective Decontamination of the Digestive Tract
Preemptive Systemic Antibiotic Therapy
Additional Data
Review Article Recommendations
Guidelines
Actual Practice
Conclusions
Key References
References
77 Splenic Abscess
Short View Summary
Epidemiology
Pathogenesis
Microbiology
Clinical Manifestations
Diagnosis
Ultrasonography
Computed Tomography
Magnetic Resonance Imaging
Therapy
Key References
References
78 Appendicitis
Short View Summary
Epidemiology
Pathogenesis
Microbiology
Clinical Manifestations
Diagnosis
Therapy
Key References
References
79 Diverticulitis and Neutropenic Enterocolitis
Short View Summary
Diverticulitis
Epidemiology
Pathogenesis
Microbiology
Clinical Manifestations
Diagnosis
Therapy
Neutropenic Enterocolitis (Typhlitis)
Pathogenesis
Clinical Manifestations
Diagnosis
Therapy
Key References
References
G Cardiovascular Infections
80 Endocarditis and Intravascular Infections
Short View Summary
Infective Endocarditis
Epidemiology
Age
Health Care–Associated Infective Endocarditis
Pattern of Valvular Involvement
Predisposing Factors
Pathogenesis and Pathophysiology
Nonbacterial Thrombotic Endocarditis
Hemodynamic Factors
Transient Bacteremia
Microorganism–Nonbacterial Thrombotic Endocarditis Interaction
Viridans-Group Streptococcal Interactions With Platelets
Adhesion to Nonbacterial Thrombotic Endocarditis by Other Organisms
Pathogenesis of Staphylococcus aureus Infective Endocarditis
Effect of Antibiotics on Development of Infective Endocarditis
Platelets and the Pathogenesis of Infective Endocarditis
Interactions Between Bacteria and the Growing Vegetation
Immunopathologic Factors
Pathologic Changes
Heart
Kidney
Mycotic Aneurysms
Central Nervous System
Spleen
Lung
Skin
Eye
Clinical Manifestations
Cardiac Murmurs
Peripheral Manifestations of Infective Endocarditis
Splenomegaly
Musculoskeletal Manifestations
Embolic Events
Neurologic Manifestations
Renal Manifestations
Infective Endocarditis in Drug Addicts
Laboratory Findings
Special Diagnostic Tests
Echocardiography
Transesophageal Echocardiography
Cardiac Catheterization
Diagnostic Criteria
Etiologic Agents
Streptococci
Enterococci
Streptococcus pneumoniae
β-Hemolytic Streptococci
Gemella
Aerococci
Staphylococci
Coagulase-Negative Staphylococci
Gram-Negative Bacilli
HACEK Group Bacteria (Haemophilus, Aggregatibacter [Formerly Actinobacillus spp.], Cardiobacterium, Eikenella, Kingella)
Other Gram-Negative Bacteria
Gram-Positive Bacilli
Anaerobic Bacteria
Other Bacteria
Coxiella burnetii
Chlamydia psittaci
Tropheryma whipplei
Brucella species
Unusual Bacterial Causes of Infective Endocarditis
Fungi
Viruses
Culture-Negative Endocarditis
Polymicrobial Endocarditis
Etiology of Infective Endocarditis in Injection Drug Users
Therapy for Infective Endocarditis
General Principles
Tests Useful for Antimicrobial Treatment Monitoring
Antimicrobial Therapy
Penicillin-Sensitive Streptococcal Endocarditis
Endocarditis Caused by Streptococci With Penicillin Minimal Inhibitory Concentration Greater Than 0.5 µg/mL or by Enterococci
Alternatives to Full-Course Aminoglycoside Therapy for Enterococcal Infective Endocarditis
Staphylococcal Endocarditis
Daptomycin for Staphylococcal Infective Endocarditis
Other Antibiotics for Staphylococcal Infective Endocarditis
Therapy for Highly Resistant Staphylococci
Treatment of S. aureus Bacteremia Without Proven Infective Endocarditis
Coagulase-Negative Staphylococci
Endocarditis Due to Enterobacteriaceae or Pseudomonas Species
Endocarditis Due to Anaerobic Bacilli
Pneumococcal, Gonococcal, and Meningococcal Endocarditis
Fungal Endocarditis
Q Fever Endocarditis
Infective Endocarditis Due to Chlamydiae
Culture-Negative Endocarditis
Surgical Therapy
Suppurative Thrombophlebitis
Epidemiology
Pathogenesis
Pathologic Changes
Clinical Manifestations
Laboratory Findings
Etiologic Agents
Presumptive Therapy
Prevention
Infective Endarteritis and Mycotic Aneurysms
Epidemiology
Pathogenesis
Pathologic Changes
Clinical Manifestations
Laboratory Findings
Etiologic Agents
Therapy
Key References
References
81 Prosthetic Valve Endocarditis
Short View Summary
Prosthetic Valves
Mechanical Valves
Bioprosthetic Valves
Transcatheter Expandable Valves
Epidemiology
Prosthetic Valve Endocarditis After Transcatheter Valve Replacement
Microbiology
Early- and Late-Onset Prosthetic Valve Endocarditis
Health Care–Associated Prosthetic Valve Endocarditis
Community-Acquired Prosthetic Valve Endocarditis
Outbreaks of Nontuberculous Mycobacterial Infections
Pathogenesis
Microbial Adherence
Formation and Growth of Vegetations
Persistence and Growth of Microorganisms
Tissue Destruction and Invasion
Pathology
Clinical Presentation
Diagnosis
Echocardiography
Nuclear Medicine Imaging Techniques
Labeled Leukocyte Scintigraphy
Positron Emission Tomography/ Computer Tomography
Limitations of Positron Emission Tomography/Computer Tomography
Identification of the Pathogen
Blood Cultures
Valve Culture
Serologic Methods
Broad-Range Polymerase Chain Reaction Based on the Bacterial 16S rRNA Gene
Histology
Antimicrobial Therapy
Staphylococcal Prosthetic Valve Endocarditis
Streptococcal Prosthetic Valve Endocarditis
Enterococcal Prosthetic Valve Endocarditis
HACEK Prosthetic Valve Endocarditis
Diphtheroid Prosthetic Valve Endocarditis
Enteric Gram-Negative Bacillary Prosthetic Valve Endocarditis
Fungal Prosthetic Valve Endocarditis
Prosthetic Valve Endocarditis Due to Nontuberculous Mycobacteria
Culture-Negative Prosthetic Valve Endocarditis
Surgical Intervention
Indications for Surgical Intervention
Severe Heart Failure Due to Prosthetic Valve Dysfunction
Perivalvular Extension of Infection
High-Grade Pathogens
Multiple Emboli
Timing of Surgery
Timing of Surgery in Patients With Central Nervous System Embolism
Surgical Treatment
Outcome of Patients Treated Surgically for Prosthetic Valve Endocarditis
Duration of Antimicrobial Therapy Postoperatively
Anticoagulation Therapy
Prevention
Key References
References
82 Infections of Nonvalvular Cardiovascular Devices
Short View Summary
Cardiovascular Implantable Electronic Devices
Epidemiology of Cardiovascular Implantable Electronic Device Infections
Pathogenesis of Cardiovascular Implantable Electronic Device Infections
Risk Factors for Cardiovascular Implantable Electronic Device Infections
Microbiology of Cardiovascular Implantable Electronic Device Infection
Clinical Manifestations of Cardiovascular Implantable Electronic Device Infection
Diagnosis of Cardiovascular Implantable Electronic Device (CIED) Infection
Role of Echocardiography in Diagnosis of Cardiovascular Implantable Electronic Device Infection
Complications of Cardiovascular Implantable Electronic Device Infection
Management of Cardiovascular Implantable Electronic Device Infection
Prevention
Left Ventricular Assist Devices
Epidemiology of Left Ventricular Assist Device Infections
Pathogenesis of Left Ventricular Assist Device Infections
Risk Factors for Left Ventricular Assist Device Infections
Clinical Manifestations of Left Ventricular Assist Device Infections
Microbiology of Left Ventricular Assist Device Infections
Management of Left Ventricular Assist Device Infections
Prevention
Prosthetic Vascular Grafts
Epidemiology of Prosthetic Vascular Graft Infection
Pathogenesis of Prosthetic Vascular Graft Infection
Risk Factors for Prosthetic Vascular Graft Infection
Microbiology of Prosthetic Vascular Graft Infection
Clinical Manifestations of Prosthetic Vascular Graft Infection
Diagnosis of Prosthetic Vascular Graft Infection
Management of Prosthetic Vascular Graft Infection
Surgical Management of Extracavitary Prosthetic Vascular Graft Infection
Antimicrobial Management of Extracavitary Prosthetic Vascular Graft Infection
Surgical Management of Intraabdominal Prosthetic Vascular Graft Infection
Antimicrobial Management of Intraabdominal Prosthetic Vascular Graft Infection
Management of Intrathoracic Prosthetic Vascular Graft Infection
Prevention
Hemodialysis Prosthetic Vascular Grafts
Epidemiology
Clinical Manifestations
Management
Prevention
Invasive Nonsurgical Cardiologic Procedures
Epidemiology
Risk Factors
Clinical Manifestations
Microbiology
Treatment
Prevention
Coronary Artery Stents
Peripheral Vascular Stents
Epidemiology
Diagnosis
Management and Outcome
Prevention
Vascular Closure Devices
Epidemiology and Clinical Manifestations
Microbiology
Management
Prevention of Percutaneous Vascular Closure Device–Related Infection
Intraaortic Balloon Pumps
Vena Cava Filters
Dacron Carotid Patches
Clinical Manifestations
Management
Cardiac Suture Line Infections
Clinical Manifestations
Management of Cardiac Suture Line Infections
Closure Device Treatment of Patent Ductus Arteriosus, Atrial Septal Defect, and Ventricular Septal Defect
Key References
References
83 Prevention of Infective Endocarditis
Short View Summary
Pathogenesis of Infective Endocarditis in the Context of Prevention
Estimation of the Risk for Infective Endocarditis
Procedures at Risk for Causing Infective Endocarditis
Preexisting Cardiac Conditions
Indirect Evidence Regarding the Risk for Infective Endocarditis Posed by Dental Procedures and the Efficacy of Prophylaxis
Cohort Studies
Case-Control Studies
In Vitro Antibiotic Susceptibility Studies
Experimental Infective Endocarditis
Potential Interventions to Prevent Endocarditis
Correction of Predisposing Cardiac Conditions
Minimization of Portals of Entry for Microorganisms
Prevention of Health Care–Associated Infections
Administration of Systemic Antibiotics
Evolution of Clinical Practice in Prevention of Infective Endocarditis
Historical Trends Over 7 Decades
Current Guidelines
Timing, Dosage and Duration of Antibiotic Prophylaxis
Cost-Benefit and Cost-Effectiveness Analyses
Specific Issues in Prevention of Infective Endocarditis
Prevention of Health Care–Associated Infective Endocarditis
Prevention of Infective Endocarditis Due to the Implantation of Cardiac Implantable Electronic Devices
Prevention of Infective Endocarditis Due to Valvuloplasty and Valve Replacement
Prevention of Infective Endocarditis in Patients With Prosthetic Heart Valves
Cardiac Assist Devices and Artificial Hearts
Cardiac Transplantation
Medical Diagnostic Procedures
Invasive Procedures Involving Infected or Nonsterile Sites
Prophylaxis of Infective Endocarditis for Children
Anticoagulant Therapy
Medicolegal Liability Issues
New Horizons for Antibiotic Prophylaxis of Infective Endocarditis
Oral Hygiene
“Big Data” as a Vehicle to Assess the Usefulness of Infective Endocarditis Prevention Measures
Novel Approaches
Conclusion
Key References
References
84 Myocarditis and Pericarditis
Short View Summary
Myocarditis
Etiologic Agents
Nonviral Pathogens That Cause Myocarditis
Pathology and Pathogenesis
Clinical Manifestations
Diagnosis
Treatment
Prevention
Pericarditis
Etiologic Agents
Pathology, Pathogenesis, and Pathophysiology
Clinical Manifestations
Diagnosis
Treatment
Key References
References
85 Mediastinitis
Short View Summary
Anatomic Considerations
Acute Mediastinitis
Epidemiology and Pathogenesis
Mediastinitis Secondary to Esophageal Perforation
Mediastinitis Secondary to Head and Neck Infections or From Other Sites
Mediastinitis Secondary to Cardiothoracic Surgery
Risk Factors for Mediastinitis
Pathogenesis
Bacteriology
Clinical Manifestations and Diagnosis
Mediastinitis Caused by Bacillus anthracis
Cardiac Surgery–Related Mediastinitis
Therapy
Mediastinitis Due to Esophageal Perforation
Mediastinitis Due to Head and Neck Infection
Cardiac Surgery–Related Mediastinitis
Prevention of Mediastinitis After Cardiac Surgery
Complications and Prognosis
Chronic/Fibrosing Mediastinitis
Definition and Etiology
Manifestations and Diagnosis
Pathogenesis
Treatment
Key References
References
H Central Nervous System Infections
86 Approach to the Patient With Central Nervous System Infection
Clinical Manifestations
Meningitis
Encephalitis
Focal Central Nervous System Syndromes
Lumbar Puncture
Opening Pressure and Appearance
Cell Count
Glucose and Protein
Other Cerebrospinal Fluid Tests
Neuroimaging Studies
Management
Antimicrobial Therapy
Surgical Therapy
Adjunctive Therapy
References
87 Acute Meningitis
Short View Summary
Defining Acute Meningitis
Epidemiology and Etiology
Viral Meningitis
Enteroviruses
Herpesviruses
Arboviruses
Other Viruses
Bacterial Meningitis
Overview of Bacterial Meningitis
Haemophilus influenzae
Neisseria meningitidis
Streptococcus pneumoniae
Listeria monocytogenes
Streptococcus agalactiae (Group B Streptococcus)
Aerobic Gram-Negative Bacilli
Staphylococci
Other Bacteria
Spirochetal Meningitis
Treponema pallidum
Borrelia burgdorferi
Protozoal and Helminthic Meningitis
Amebas
Angiostrongylus cantonensis
Pathogenesis and Pathophysiology
Viral Meningitis
Initiation of Infection
Viremia and Central Nervous System Invasion
Virus Spread Within the Central Nervous System
Bacterial Meningitis
Mucosal Colonization and Systemic Invasion
Intravascular Survival
Meningeal Invasion
Bacterial Survival Within the Subarachnoid Space
Induction of Subarachnoid Space Inflammation
Alterations of the Blood-Brain Barrier
Cerebral Edema and Increased Intracranial Pressure
Alterations in Cerebral Blood Flow
Clinical Manifestations
Viral Meningitis
Enteroviruses
Herpesviruses
West Nile virus
Mumps Virus
Bacterial Meningitis
Neonates, Infants, and Children
Adults
Older Adults
Underlying Conditions
Pathogen-Specific Findings
Spirochetal Meningitis
Treponema pallidum
Neuroborreliosis
Protozoal and Helminthic Meningitis
Amebas
Angiostrongylus cantonensis
Diagnosis
Viral Meningitis
Cerebrospinal Fluid Examination
Bacterial Meningitis
Cerebrospinal Fluid Examination
Differentiation of Bacterial From Viral Meningitis
Radiography
Spirochetal Meningitis
Treponema pallidum
Borrelia burgdorferi
Protozoal and Helminthic Meningitis
Amebas
Angiostrongylus cantonensis
Initial Management of Patients With Acute Meningitis
Who Should Have a Lumbar Puncture?
Who Should Undergo Cranial Computed Tomography Before Lumbar Puncture
Empirical Therapy of Community-Acquired Acute Bacterial Meningitis in Adults
Selecting the Right Antimicrobial
Adjunctive Corticosteroids
Experimental Data
Clinical Studies of Corticosteroids in Infants and Children
Clinical Studies of Corticosteroids in Adults
Antimicrobial Therapy
Viral Meningitis
Bacterial Meningitis
Principles of Therapy
Specific Antimicrobial Therapy
Haemophilus influenzae
Neisseria meningitidis
Streptococcus pneumoniae
Listeria monocytogenes
Streptococcus agalactiae
Aerobic Gram-Negative Bacilli
Staphylococci
Other Bacteria
Duration of Therapy
Spirochetal Meningitis
Treponema pallidum
Borrelia burgdorferi
Protozoal and Helminthic Meningitis
Amebas
Angiostrongylus cantonensis
Adjunctive Therapy
Viral Meningitis
Bacterial Meningitis
Antiinflammatory Agents
Reduction of Intracranial Pressure
Surgery
Helminthic Meningitis
Prevention
Bacterial Meningitis
Haemophilus influenzae
Chemoprophylaxis
Neisseria meningitidis
Chemoprophylaxis
Streptococcus pneumoniae
Chemoprophylaxis
Streptococcus agalactiae
Chemoprophylaxis
Basilar Skull Fracture
Haemophilus influenzae
Immunoprophylaxis
Neisseria meningitidis
Immunoprophylaxis
Streptococcus pneumoniae
Immunoprophylaxis
Key References
References
88 Chronic Meningitis
Short View Summary
Distinction From Other Chronic Central Nervous System Infections
Myelitis, Myeloradiculitis, and Polyradiculitis
Encephalitis
Brain Abscess
Chronic Meningitis
Clinical Manifestations
Diagnosis
Physical Examination
History
Imaging
Laboratory Findings
Cerebrospinal Fluid
Peripheral Blood
Brain Biopsy
Differential Diagnosis
Cryptococcus Meningitis
Coccidioides Meningitis
Histoplasma Meningitis
Candida Meningitis
Sporothrix Meningitis
Blastomyces Meningitis
Phaeohyphomycotic Meningitis
Other Molds Causing Meningitis
Mycobacterium tuberculosis Meningitis
Treponema pallidum Meningitis
Borrelia burgdorferi
Tropheryma whipplei Meningitis
Nocardia and Actinomyces Meningitis
Brucella Meningitis
Amebic Granulomatous Meningitis
Angiostrongylus cantonensis Meningitis
Taenia solium Meningitis
Enteroviral Meningitis
Postneurosurgical Meningitis
Sarcoidosis Meningitis
Vogt-Koyanagi-Harada Syndrome Meningitis
Behçet Syndrome Meningitis
Neoplastic Meningitis
IgG4-Related Hypertrophic Pachymeningitis
Empirical Therapy for Presumed Tuberculous Meningitis
Key References
References
89 Encephalitis
Short View Summary
Clinical Syndromes
Autoimmune Encephalitis
General Clinical Approach
Clinical Manifestations
Diagnostic Tests
Neuroimaging
Cerebrospinal Fluid Analysis
Cerebrospinal Fluid Profile
Polymerase Chain Reaction and Antibody Studies
Future diagnostic approaches.
Electroencephalography
Other Diagnostic Studies
Management
Viral Etiology of Encephalitis
Herpesviruses
Herpes Simplex Virus Types 1 and 2
Herpes Simplex Virus Pathogenesis
Herpes Simplex Virus Encephalitis: Clinical Presentation
Herpes Simplex Virus Encephalitis: Diagnosis
Herpes Simplex Virus Encephalitis: Treatment and Outcomes
HSV-2 Central Nervous System Disease
Herpes Simplex Virus Myelitis
Varicella-Zoster Virus
Varicella-Zoster Virus Pathogenesis and Central Nervous System Disease
Varicella-Zoster Virus Vasculopathy
Varicella-Zoster Virus Meningitis
Varicella-Zoster Virus Central Nervous System Disease Treatment
Cytomegalovirus
Epstein-Barr Virus
Human Herpesvirus 6
Herpesvirus B
Vector-Borne Viral Infections
Encephalitic Arbovirus Pathogenesis
West Nile Virus (Also See Chapter 153)
West Nile Virus Pathogenesis
West Nile Virus: Infection Clinical Features
West Nile Virus Infection: Diagnosis
West Nile Virus: Prevention and Treatment
West Nile Virus: Infection Outcome
St. Louis Encephalitis
St. Louis Encephalitis Virus Infection: Clinical Features
St. Louis Encephalitis Virus Infection: Diagnosis
Zika Virus (Also See Chapter 153)
Zika Virus Clinical Features
Zika Virus: Transmission
Zika Virus Infection: Diagnosis and Management
Eastern Equine Encephalitis Virus
Western Equine Encephalitis
Venezuelan Equine Encephalitis
Chikungunya
California Encephalitis Group
Japanese Encephalitis
Influenza
Colorado Tick Fever Virus (See Chapter 149)
Enteroviruses
Poliovirus
Nonpoliovirus Enteroviruses
Rabies Virus
Measles Virus
Key References
References
90 Brain Abscess
Short View Summary
Epidemiology and Etiology
Bacterial Brain Abscess
Fungal Brain Abscess
Protozoal and Helminthic Brain Abscess
Pathogenesis and Pathophysiology
Pathogenesis
Natural History of Infection
Clinical Presentation
Diagnosis
Initial Management of the Patient With Brain Abscess
Therapy
Bacterial Brain Abscess
Antimicrobial Therapy
Surgical Therapy
Fungal Brain Abscess
Key References
References
91 Subdural Empyema, Epidural Abscess, and Suppurative Intracranial Thrombophlebitis
Short View Summary
Subdural Empyema
Epidemiology and Etiology
Clinical Features
Diagnosis
Management and Outcome
Epidural Abscess
Epidemiology and Etiology
Clinical Features
Diagnosis
Management and Outcome
Suppurative Intracranial Thrombophlebitis
Epidemiology and Etiology
Clinical Features
Diagnosis
Management and Outcome
Key References
References
92 Cerebrospinal Fluid Shunt and Drain Infections
Short View Summary
Epidemiology
Etiology
Pathogenesis
Clinical Features
Diagnosis
Therapy
Antimicrobial Therapy
Intraventricular and Intrathecal Antimicrobial Therapy
Shunt Removal
Duration of Antimicrobial Therapy and Shunt Reimplantation
Surgical Management of Ventriculoperitoneal Shunt–Related Peritoneal Pseudocyst
Surgical Management of Intraventricular Empyema
Prevention
Antimicrobial Prophylaxis
Antimicrobial-Impregnated Catheters
Combined Interventions
Key References
References
I Skin and Soft Tissue Infections
93 Cellulitis, Necrotizing Fasciitis, and Subcutaneous Tissue Infections
Short View Summary
Cellulitis and Superficial Infections
Primary Pyodermas
Impetigo
Pathologic Characteristics and Pathogenesis
Clinical Manifestations
Laboratory Findings
Etiologic Agents
Differential Diagnosis
Presumptive Therapy
Bullous Impetigo
Clinical Manifestations
Presumptive Therapy
Staphylococcal Scalded Skin Syndrome
Clinical Manifestations
Presumptive Therapy
Staphylococcal Scarlet Fever
Toxic Shock Syndrome
Folliculitis
Furuncles and Carbuncles
Definition and Pathologic Characteristics
Clinical Manifestations
Presumptive Therapy
Ecthyma
Chancriform Lesions: Anthrax
Pathogenesis
Clinical Manifestations
Presumptive Therapy
Erysipelas
Clinical Manifestations
Differential Diagnosis
Presumptive Therapy
Cellulitis
Clinical Manifestations
Presumptive Therapy
Membranous Ulcers
Cutaneous Diphtheria
Clinical Manifestations
Laboratory Findings
Differential Diagnosis
Presumptive Therapy
Infectious Gangrene (Gangrenous Cellulitis)
Pathologic Characteristics and Pathogenesis
Clinical Manifestations
Streptococcal gangrene.
Progressive bacterial synergistic gangrene.
Gas gangrene, anaerobic cellulitis, and other forms of crepitant cellulitis.
Gangrenous cellulitis in immunocompromised hosts.
Differential Diagnosis
Presumptive Therapy
Erythrasma
Secondary Bacterial Infections Complicating Preexisting Skin Lesions
Diabetic Foot and Other Chronic Superficial Skin Ulcers
Decubitus Ulcers
Diabetic Ulcers
Occupation-Related Ulcers
Posttraumatic Opportunistic Skin Infections in Immunocompromised Patients
Bacillary Angiomatosis in Patients With Acquired Immunodeficiency Syndrome
Hidradenitis Suppurativa
Infected Epidermal Cysts
Self-Induced Skin Infections
Cutaneous Involvement in Systemic Bacterial and Mycotic Infections
Bacteremias
Staphylococcus aureus
Pseudomonas aeruginosa
Neisseria meningitidis
Neisseria gonorrhoeae
Salmonella enterica Serovar Typhi
Haemophilus influenzae
Helicobacter cinaedi
Infective Endocarditis
Fungemias: Candida albicans and Other Yeasts
Subcutaneous Tissue Infections and Abscesses
Clostridial Anaerobic Cellulitis
Pathologic Characteristics and Pathogenesis
Clinical Manifestations
Etiologic Agents
Differential Diagnosis
Presumptive Therapy
Nonclostridial Anaerobic Cellulitis
Necrotizing Fasciitis
Clinical Manifestations
Fournier gangrene.
Other special anatomic forms of necrotizing fasciitis.
Other microbial causes of necrotizing fasciitis.
Differential Diagnosis
Presumptive Therapy
Synergistic Necrotizing Cellulitis
Clinical Manifestations
Etiologic Agents
Presumptive Therapy
Miscellaneous Infections Secondary to Trauma
Bite Infections
Burn Infections
Injection Site Abscesses
Factitial Disease (Self-Induced Abscesses)
Subcutaneous Infections Originating in Contiguous Foci
Osteomyelitis
Actinomycosis
Primary Pyodermas
Subcutaneous Abscesses in the Course of Bacteremic Infections
Mycetoma
Key References
References
94 Myositis and Myonecrosis
Short View Summary
Pyomyositis
Pathogenesis and Pathologic Characteristics
Clinical Manifestations
Etiologic Agents
Differential Diagnosis
Diagnosis
Empirical Therapy
Group a Streptococcal Necrotizing Myositis
Gas Gangrene (Clostridial Myonecrosis)
Pathogenesis and Pathologic Characteristics
Clinical Manifestations
Laboratory Findings
Etiologic Agents
Differential Diagnosis
Empirical Therapy
Nonclostridial (Crepitant) Myositis
Anaerobic Streptococcal Myonecrosis
Synergistic Nonclostridial Anaerobic Myonecrosis
Infected Vascular Gangrene
Aeromonas hydrophila Myonecrosis
Psoas Abscess
Other Specific Sites of Muscle Abscesses
Myalgias
Influenza
Infective Endocarditis
Toxoplasmosis
Other Causes
Pleurodynia Syndromes
Myalgias With Eosinophilia (Parasitic Myositis)
Trichinosis
Cysticercosis (Cysticercus cellulosae Myositis)
Muscle Degeneration Associated With Infections at Other Sites
Acute Rhabdomyolysis
Muscle Proteolysis and Mediators of Fever in Patients With Sepsis
Key References
References
95 Lymphadenitis and Lymphangitis
Short View Summary
Lymphadenitis
Pathogenesis and Pathologic Changes
Acute Lymphadenitis
Chronic Lymphadenitis
Clinical Manifestations
Acute Regional Lymphadenitis Due to Pyogenic Bacteria
Syndromes Due to Suppurative Lymphadenitis at Specific Anatomic Sites
Cervical Lymphadenitis
Acute Axillary Lymphadenitis
Subpectoral Lymphadenitis
Deep Neck Space Lymphadenitis
Acute Mediastinal Lymphadenitis
Acute Suppurative Epitrochlear Lymphadenitis
Suppurative Iliac Lymphadenitis
Acute Regional Lymphadenitis Due to Infecting Agents Other Than Pyogenic Bacteria
Specific Types of Nonpyogenic Regional Lymphadenitis
Scrofula (Tuberculous Cervical Lymphadenitis)
Granulomatous Lymphadenitis Caused by Nondiphtheria Corynebacteria
Oculoglandular (Parinaud) Syndrome
Cat-Scratch Disease
Mediastinal Lymphadenopathy
Inguinal Buboes of Sexually Transmitted Disease
Inguinal Buboes of Other Than Sexually Transmitted Disease Origin
Generalized Lymphadenitis Associated With Systemic Infections
Recurrent Lymphadenitis
Periodic Fever, Aphthous Ulcers, Pharyngitis, and Adenitis Syndrome
Filarial Lymphangitis
Etiologic Agents and Differential Diagnosis
Generalized Lymphadenopathy With Acquired Immunodeficiency Syndrome
Presumptive Treatment of Lymphadenitis
Lymphangitis
Pathologic Changes and Pathogenesis
Clinical Findings
Acute Lymphangitis
Chronic Granulomatous Lymphangitis
Pseudolymphangitis
Etiologic Agents
Differential Diagnosis
Presumptive Therapy
Key References
References
J Gastrointestinal Infections and Food Poisoning
96 Syndromes of Enteric Infection
Short View Summary
Occurrence and Scope of Gastrointestinal Infections
Occurrence and Scope of Gastrointestinal Infections in High-Income Countries
Pathogens Associated With Gastrointestinal Infections
Environmental Risk Factors for Gastrointestinal Infection
Host Factors in Gastrointestinal Infection
Age
Gastric Acidity and Physical Barriers
Intestinal Microbiome
Immunocompromise
Genetic Determinants
Nutritional Status
Microbial Factors in Gastrointestinal Infection
Inoculum Size
Adherence/Attachment
Invasion
Toxins
Neurotoxins
Enterotoxins
Cytotoxins
Major Clinical Syndromes
Acute Vomiting
Acute Watery Diarrhea
Diarrhea With Fever
Persistent Diarrhea
Enteric Fever
Complications of Acute Enteric Infection
Asymptomatic Passage of Enteropathogens
Diagnostic Approach to Enteric Infections
Therapy for Enteric Infections
Prevention and Control of Enteric Infections
Key References
References
97 Esophagitis
Short View Summary
Clinical Manifestations
Specific Etiologic Agents
Candida Esophagitis
Diagnosis
Radiology
Cytomegalovirus Esophagitis
Herpes Simplex Virus Esophagitis
Diagnosis
Aphthous (Idiopathic) Ulceration of the Esophagus
Management of Esophageal Infection
General Considerations in Therapy
Esophagitis in Patients With Acquired Immunodeficiency Syndrome
Key References
References
98 Diarrhea With Little or No Fever
Short View Summary
Epidemiology of Acute Noninflammatory Diarrhea
Community-Acquired Diarrhea
Acute Pediatric Diarrhea
Diarrhea Caused by Rotavirus
Acute Nausea and Vomiting (Winter Vomiting Disease)
Norovirus
Sapovirus
Diarrhea Caused by Astrovirus, Adenovirus, and Other Possible Viral Etiologies
Cryptosporidiosis
Diarrhea Due to Enteropathogenic Bacteria
Diarrhea in Adults
Diarrhea in Immunocompromised Patients
Patients With HIV Infection
Patients With Solid-Organ Transplants and Others Receiving Immunosuppressants
Travel-Associated Diarrhea (Turista)
Diarrhea in Institutions
Epidemic Nosocomial Diarrhea in Newborns
Hospitals
Long-Term Care Facilities
Daycare Centers
Treatment of Acute Noninflammatory Diarrhea
Chronic Noninflammatory Diarrhea
Bacterial Overgrowth Syndromes
Brainerd Diarrhea
Other Noninfectious Mimics of Gastroenteritis
Acknowledgment
Key References
References
99 Acute Dysentery Syndromes (Diarrhea With Fever)
Short View Summary
Definition
Epidemiology
Microbiology and Pathogenesis of the Major Causes of Acute Dysenteric Syndromes
Shigella spp. and Enteroinvasive Escherichia coli
Shiga Toxin–Producing Escherichia coli
Enteropathogenic and Enteroaggregative Escherichia coli
Campylobacter Enteritis
Clostridioides difficile Colitis
Vibriosis
Salmonellosis and Enteric Fever
Yersiniosis
Amebiasis
Diagnosis
Therapy
Prevention
Other Acute Infectious/Inflammatory Processes Involving the Intestinal Tract
Gonococcal Proctitis
Unusual Causes of Dysentery
Necrotizing Enterocolitis in the Newborn
Darmbrand, Pig-Bel, Necrotizing Enteritis in Adults (Enteritis Necroticans)
Chronic Infectious/Inflammatory Processes Involving the Intestinal Tract
Syphilis
Gastrointestinal Tuberculosis
Key References
References
100 Typhoid Fever, Paratyphoid Fever, and Typhoidal Fevers
Short View Summary
Enteric Fever (Typhoid and Paratyphoid Fever)
History
Etiologic Agents of Enteric Fever
Nomenclature and Classification of Typhoidal Salmonella enterica
Clinical Distinction Between Typhoidal and Nontyphoidal Salmonella enterica
Genomic Features
Epidemiology
Burden and Distribution
Severity
Source of Infection
Mode of Transmission
Acquisition of Disease in Areas Where Enteric Fever Occurs Sporadically
Antibiotic Resistance and Emergence of Pandemic Salmonella Typhi
Host Factors and Susceptibility to Infection
Pathogenesis
Invasion
Latency and Dissemination
Intestinal and Other Local Pathology
Relapse and Chronic Carriage
Clinical Manifestations
Uncomplicated Typhoid Fever
Laboratory Findings in Uncomplicated Infection
Severe Illness
Gastrointestinal Complications
Neurologic Complications
Metastatic Pyogenic Complication
Diagnosis
Culture-Based Diagnostics
Serologic Tests
Molecular Approaches
Screening for Chronic Carriage
Management
Chloramphenicol, Ampicillin, and Trimethoprim-Sulfamethoxazole
Fluoroquinolones
Cephalosporins
Azithromycin
Other Antibiotics
Adjunctive Therapy
Supportive Care and Management of Complications
Treatment of Relapse and Chronic Carriage
Prevention
Differential Diagnosis of Enteric and Typhoidal Fevers
Bacteremia Associated With Nontyphoidal Salmonella
Typhoidal Fever
Additional Causes of Prolonged or Persistent Fever
Assessing an Individual With an Acute Febrile Illness in a Resource-Limited Area or After International Travel
Fever and Mesenteric Adenitis or Ileocecitis
Fever, Abdominal Pain, and Peripheral Eosinophilia
Key References
References
101 Foodborne Disease
Short View Summary
Clinical Manifestations and Pathogenesis
Foodborne Syndromes Caused by Microbial Agents or Their Toxins
Nausea and Vomiting Lasting Less Than 24 Hours
Watery Diarrhea Without Fever Lasting 1 to 2 Days
Watery Diarrhea and Abdominal Cramps Lasting More Than 2 Days
Diarrhea, Abdominal Cramps, and Fever
Bloody Diarrhea With Minimal Fever
Persistent Diarrhea Lasting 2 or More Weeks
Cranial Nerve Palsies and Descending Paralysis
Systemic Illness
Postinfection Syndromes
Foodborne Syndromes Caused by Nonbacterial Toxins
Nausea, Vomiting, and Abdominal Cramps Associated With Heavy Metal Ingestion
Histamine Reaction After Eating Seafood
Paresthesias After Eating Shellfish
Gastrointestinal, Neurologic, and Cardiovascular Symptoms After Eating Fish
Rapid Paralysis After Eating Puffer Fish
Diarrhea and Chills Within 12 Hours After Eating Shellfish
Diarrhea, Abdominal Cramps, Memory Loss, and Disorientation After Eating Shellfish
Abdominal Cramps, Vomiting, and Diarrhea Followed by Hepatorenal Failure
Miscellaneous Other Mushroom Poisoning Syndromes With Onset Within 2 Hours
Epidemiology
Foods
Nonfoodborne Transmission
Vulnerable Populations
Seasonality
Geographic Location
Epidemiologic Assessment
Laboratory Diagnosis
Diagnosis in Foodborne Outbreaks
Specific Considerations About Important Pathogens
Staphylococcus aureus
Bacillus cereus
Clostridium perfringens
Classic Bacterial Enteropathogens
Botulism
Protozoa
Heavy Metals
Unknown or Rare Causes
Therapy
Surveillance
Prevention
Key References
References
102 Tropical Sprue and Environmental Enteric Dysfunction
Short View Summary
Tropical Sprue
Environmental Enteric Dysfunction
Exposures/Epidemiology
Tropical Sprue
Environmental Enteric Dysfunction
Clinical Features
Tropical Sprue
Environmental Enteric Dysfunction
Pathogenesis
Tropical Sprue
Intestinal Abnormalities
Tropical Sprue
Histopathology
Tropical Sprue
Environmental Enteric Dysfunction
Diagnosis
Tropical Sprue
Environmental Enteric Dysfunction
Increased Intestinal Permeability/Impaired Gut Barrier Integrity
Intestinal Damage and Repair
Mucosal and Systemic Inflammation
Microbial Translocation and Immune Activation
Fecal Messenger mRNA Transcripts
Therapy
Tropical Sprue
Environmental Enteric Dysfunction
Key References
References
K Bone and Joint Infections
103 Infectious Arthritis of Native Joints
Short View Summary
Acute Bacterial Arthritis
Epidemiology
Route of Infection
Predisposing Host Factors
Nongonococcal Arthritis
Pathophysiology
Microbiology
Gram-Positive Bacteria
Gram-Negative Bacteria
Other Bacteria
Clinical Manifestations
Joints Involved
Clinical Presentation
Laboratory Findings
Microbiologic Diagnosis
Conventional culture.
Molecular tests.
Radiographic Features
Gonococcal Arthritis
Epidemiology
Pathogenesis
Antimicrobial Resistance
Clinical Manifestations
Laboratory Testing
Septic Arthritis in Persons Who Inject Drugs
Management
Initial Approach to the Patient
Patient Assessment
Laboratory Assessment
Synovial Fluid Assessment
Other Analysis
Differential Diagnosis
Crystalline Arthritis
Other Causes of Arthritis
Therapy
Joint Drainage
Antimicrobial Therapy
Initial antimicrobial selection.
Antimicrobial deescalation.
Directed therapy for MRSA infections.
Directed therapy for other situations.
Duration of therapy.
Adjuvant Therapy
Viral Arthritis
Parvovirus B19
Alphaviruses, Including Chikungunya
Other Causes of Viral Arthritis
Chronic Infectious Arthritis
Fungal Arthritis
Candida Arthritis
Cryptococcus Arthritis
Arthritis Due to Dimorphic Fungi
Arthritis Due to Molds
Therapy for Fungal Arthritis
Mycobacterial Arthritis
Tuberculosis Arthritis
Clinical Features
Diagnosis
Treatment
Nontuberculous Mycobacterial Arthritis
Septic Bursitis
Key References
References
104 Osteomyelitis
Short View Summary
Classification
Lessons From Experimental Models
Pathogenesis in Experimental Models
Antimicrobial Therapy in Experimental Models
General Principles
General Principles of Diagnosis
General Principles of Microbiologic Diagnosis
General Principles of Therapy
Established Agents for Antimicrobial Therapy
Oral Agents for Antimicrobial Therapy
New Agents for Antimicrobial Therapy
Duration of Antimicrobial Therapy
Hyperbaric Oxygen Therapy
Osteomyelitis After a Contaminated Open Fracture
Microbiology of Osteomyelitis After Contaminated Open Fracture
Management of Open Contaminated Fractures to Prevent Osteomyelitis
Signs and Symptoms of Osteomyelitis After Contaminated Open Fracture
Management of Osteomyelitis After Contaminated Open Fracture
Vertebral Osteomyelitis and Spondylodiskitis
Clinical Signs and Symptoms of Vertebral Osteomyelitis
Microbiology of Vertebral Osteomyelitis
Diagnosis of Vertebral Osteomyelitis
Microbiologic Diagnosis of Vertebral Osteomyelitis
Therapy for Vertebral Osteomyelitis
Role of Surgery for Vertebral Osteomyelitis
Follow-Up Evaluation for Vertebral Osteomyelitis
Hardware-Associated Vertebral Infection
Osteomyelitis in Patients With Diabetes Mellitus or Vascular Insufficiency
Prevention of Diabetic Foot Osteomyelitis
Diagnosis of Osteomyelitis in Patients With Diabetes or Vascular Insufficiency
Management of Osteomyelitis in Patients With Diabetes or Vascular Insufficiency
Antimicrobial Therapy for Osteomyelitis in Patients With Diabetes or Vascular Insufficiency
Acute Hematogenous Osteomyelitis
Pathophysiology of Acute Hematogenous Osteomyelitis
Microbiology of Acute Hematogenous Osteomyelitis
Management of Acute Hematogenous Osteomyelitis
SAPHO Syndrome
Diagnosis of SAPHO Syndrome
Management of SAPHO Syndrome
Other Forms of Osteomyelitis: Specific Hosts, Unusual Locations, or Unusual Organisms
Osteitis Pubis
Sterile Osteitis Pubis
Osteomyelitis of the Clavicle
Osteomyelitis in Hemodialysis Patients
Osteomyelitis in Patients With Sickle Cell Disease
Gaucher Disease
Osteomyelitis in Injection Drug Users
Skeletal Mycobacterial Infection
Vertebral Tuberculosis (Pott disease)
Diagnosis of Tuberculous Osteomyelitis
Nontuberculous Mycobacterial Osteomyelitis
Fungal Osteomyelitis
Brodie Abscess
Culture-Negative Osteomyelitis
Summary
Key References
References
105 Orthopedic Implant– Associated Infections
Short View Summary
Periprosthetic Joint Infection
Definition
Pathogenesis
Classification
Risk Factors
Patient Characteristics
Surgery-Related Risk Factors
Postoperative Factors
Risk During Bacteremia
Microbiology
Clinical Manifestations and Differential Diagnosis
Acute Periprosthetic Joint Infection
Chronic Periprosthetic Joint Infection
Diagnostic Procedures
Blood Tests
Synovial Fluid Cell Counts
Synovial Fluid Culture
Intraoperative Samples for Culture and Histopathology
Sonication
Novel Diagnostic Procedures
α-Defensin Test
Molecular Diagnostics
Imaging Procedures
Positron Emission Tomography
Treatment Concepts
General Aspects
Débridement With Retention of Implant
One-Stage Exchange
Two-Stage Exchange
Antimicrobial Therapy
Internal Fixation– Associated Infection
Definition
Incidence of Infection
Pathogenesis and Classification
Microbiology
Clinical Manifestations
Diagnostic Procedures
Microbiology and Histopathology
Imaging
Treatment Concepts
General Aspects
Systemic Antimicrobial Therapy
Local Antimicrobial Therapy
Surgical Interventions
Plate-Associated Osteomyelitis
Intramedullary Nail–Associated Osteomyelitis
Pin-Tract Infection
Prevention in Orthopedic Surgery
Perioperative Antimicrobial Prophylaxis
Arthroplasty and Closed Fractures
Open Fractures
Prevention of Hematogenous Infection
Key References
References
L Diseases of the Reproductive Organs and Sexually Transmitted Diseases
106 Genital Skin and Mucous Membrane Lesions
Short View Summary
History of Presentation
Clinical Manifestations
Location
Pain, Dysesthesias, and Systemic Symptoms
Lymphadenopathy
Lesion Morphology
Duration
Epidemiology
Genital Lesions in Patients With Human Immunodeficiency Virus
Laboratory Testing
Therapy
Other Management Issues
Nonvenereal Genital Lesions
Key References
References
107 Urethritis
Short View Summary
Examination of the Urethra
Examination of the Urethral Specimen and Consideration of Etiologies
Noninfectious Urethritis
Infectious Urethritis
Gonococcal and Nongonococcal Urethritis
Etiology of Nongonococcal Urethritis
Postgonococcal Urethritis
Persistent or Recurrent Urethritis
Asymptomatic Urethral Infection
Urethral Syndrome and Related Diseases of Women
Complications of Urethritis
Therapy
Therapy for Sexual Partners of Men With Nongonococcal Urethritis
Reactive Arthritis
Clinical Manifestations
Laboratory Findings
Therapy
Key References
References
108 Vulvovaginitis and Cervicitis
Short View Summary
Vaginal Secretions
Approach to the Patient
History
Age
Mode of Onset
Quantity of Discharge
External Irritation
Odor
Abdominal Pain
Sexual History
Other Diseases
Medications
Physical Examination
Diagnostic Evaluation
Trichomoniasis
Epidemiology
Etiology and Pathogenesis
Diagnosis
Therapy
Pregnancy
Vulvovaginal Candidiasis
Etiology and Pathogenesis
Clinical Manifestations
Diagnosis
Therapy
Bacterial Vaginosis
Epidemiology
Pathophysiology
Dysbiosis
Hydrogen Peroxide Production
Biofilm Formation
Risk Factors
Diagnosis
Therapy
Pregnancy
Desquamative Inflammatory Vaginitis
Etiology and Pathogenesis
Diagnosis
Therapy
Cervicitis
Etiology and Pathogenesis
Symptoms and Diagnosis
Therapy
Estrogen-Deficiency Vaginitis (Genitourinary Syndrome)
Etiology and Pathogenesis
Diagnosis
Therapy
Vulvar Pain Syndrome (Formerly Vulvodynia, Vestibulodynia, Vulvar Vestibulitis, or Focal Vulvitis)
Definition and Terminology
Epidemiology
Etiology and Pathogenesis
Clinical Manifestations
Diagnosis
Therapy
Key References
References
109 Infections of the Female Pelvis
Short View Summary
Intrapartum, Postpartum, and Postabortal Infections
Postpartum Endometritis
Refractory Postpartum Fever of Undetermined Origin
Infections After Perineal Lacerations
Postabortal Infections
Surgical Site Infection After Gynecologic Surgery
Pathogenesis
Risk Factors
Cuff Cellulitis
Pelvic Abscess
Osteomyelitis Pubis
Pelvic Inflammatory Disease
Risk Factors
Diagnosis
Management of Acute Pelvic Inflammatory Disease
Management of Suspected Tubo-ovarian Abscess
Sequelae
Acknowledgment
Key References
References
110 Prostatitis, Epididymitis, and Orchitis
Short View Summary
Anatomy and Physiology of the Testes and Male Accessory Sex Organs
Host Defenses of the Male Lower Urogenital Tract
Prostatitis
Classification
Acute Bacterial Prostatitis
Chronic Bacterial Prostatitis
Chronic Prostatitis/Chronic Pelvic Pain Syndrome
Asymptomatic Inflammatory Prostatitis
Granulomatous Prostatitis
Prostatic Abscess
Epididymitis
Nonspecific Bacterial Epididymitis
Sexually Transmitted Epididymitis
Follow-Up
Orchitis
Viral Orchitis
Bacterial Orchitis
Urologic Manifestations in Men With HIV Infection
Semen as a Vector for HIV Infection
Semen as a Vector for Zika Virus Infection
Key References
References
M Eye Infections
111 Introduction to Eye Infections
Anatomy
Types of Eye Infections
Conjunctivitis
Keratitis
Endophthalmitis
Uveitis
Periocular Infections
Understanding the Ophthalmologist’s Note
Visual Acuity and Measuring Low Vision
Intraocular Pressure
Ophthalmology Examination
Case Example 1
Ophthalmologist’s Examination
Discussion
Case Example 2
Ophthalmologist’s Examination
Discussion
Ophthalmic Glossary of Interest to the Infectious Diseases Practitioner
Conclusion
112 Microbial Conjunctivitis
Short View Summary
Conjunctivitis
Anatomy and Physiology
Clinical Presentation
History and Physical Examination
Eye Pain
Itching
Visual Acuity
Conjunctival Hyperemia
Periocular and Periorbital Skin
Discharge
Conjunctival Edema (Chemosis) and Conjunctivochalasis
Conjunctival Papillae
Conjunctival Follicles
Membranes and Pseudomembranes
Conjunctival Phlyctenules and Granulomas
Corneal Involvement
Preauricular Adenopathy
Laboratory Evaluation
Viral Conjunctivitis
Adenoviral Conjunctivitis
Pharyngoconjunctival Fever
Epidemic Keratoconjunctivitis
Acute Hemorrhagic Conjunctivitis
Herpes Simplex Conjunctivitis
Varicella and Varicella-Zoster Conjunctivitis
Variola (Smallpox) Conjunctivitis
Vaccinia Conjunctivitis
Other Viral Etiologies
Chlamydial Conjunctivitis
Chlamydia trachomatis Infection
Chlamydia pneumoniae Infection
Trachoma
Adult Inclusion Conjunctivitis
Treatment of Adult Inclusion Conjunctivitis
Lymphogranuloma Venereum
Bacterial Conjunctivitis
Pathogenesis
Acute (Mucopurulent) Bacterial Conjunctivitis
Treatment of Acute Bacterial Conjunctivitis
Hyperacute (Purulent) Bacterial Conjunctivitis
Treatment of Hyperacute Bacterial Conjunctivitis
Chronic Bacterial Conjunctivitis
Treatment of Chronic Bacterial Conjunctivitis
Neonatal Conjunctivitis
Neonatal Chemical Conjunctivitis
Neonatal Chlamydial Conjunctivitis
Neonatal Gonococcal Conjunctivitis
Nongonococcal Neonatal Bacterial Conjunctivitis
Neonatal Viral (Herpetic) Conjunctivitis
Parinaud Oculoglandular Conjunctivitis
Parasitic Conjunctivitis
Leishmaniasis
Other Parasites and Ectoparasites
Fungal Conjunctivitis
Noninfectious Vision-Threatening Conditions Associated With Red Eye
Key References
References
113 Microbial Keratitis
Short View Summary
Etiologic Agents and Risk Factors
Microbial Agents
Anatomic Protection
Geographic Variation
Risk Factors
Contact Lenses
Laboratory Data and Clinical Response
Clinical Presentation
Eye Pain
Conjunctival Injection and Discharge
Corneal Infiltrates
Epithelial Defect
Stromal Suppuration
Corneal Edema
Corneal Neovascularization
Intraocular Inflammatory Reaction
Stromal Melting (Keratolysis)
Laboratory Evaluation
Stains and Media Inoculation
Viral Cultures
Bacterial Keratitis
Etiology
Pathogenesis
Geographic Variation
Gram-Positive Bacteria
Gram-Negative Bacteria
Mycobacteria
Therapy for Bacterial Keratitis
Immediate, Aggressive Therapy
Hospital Admission
Antibiotic Solutions
Local and Systemic Administration
Contact Lenses and Collagen Shields
Unique Pharmacokinetics With Topical Antibiotics
Initial Therapy
Topical Fluoroquinolones
Comparison of Fluoroquinolones and Fortified Antibiotics
Proposed Therapy Guidelines
Topical Corticosteroids
Supportive Measures
Chlamydial and Syphilitic Keratitis
Chlamydial Keratitis
Ocular Associations With Chlamydia
Syphilitic Keratitis (Interstitial Keratitis)
Therapy for Chlamydial and Syphilitic Keratitis
Therapy for Interstitial Keratitis (Syphilitic and Lyme Associated)
Viral Keratitis
Herpes Simplex Virus
Primary Herpes Simplex Virus Keratitis
Recurrent Keratitis
Stromal Inflammation and Intraocular Reaction
Neurotrophic Keratitis
Varicella-Zoster Virus
Herpes Zoster Ophthalmicus
Clinical Manifestations of Herpes Zoster Ophthalmicus
Corneal Anesthesia
Ocular Complications With Vaccinia (Smallpox) Vaccination
Vaccinia Keratitis
Adenoviral Keratitis
Differential Diagnosis of Epidemic Keratoconjunctivitis
Therapy for Viral Keratitis
Self-Limited Cases
Therapy for Herpes Simplex Virus and Varicella-Zoster Virus
Therapy for Ocular Vaccinia
Therapy for Viral Keratoconjunctivitis
Fungal Keratitis
Clinical Presentation
Fusarium Keratitis
Candida Keratitis
Therapy for Fungal Keratitis: Limited Therapy Options
Parasitic Keratitis
Acanthamoeba Keratitis
Clinical Signs and Symptoms With Acanthamoeba Keratitis
Onchocerciasis
Leishmaniasis
Microsporidia and Trypanosomes
Therapy for Parasitic Keratitis
Novel Therapeutics
Key References
References
114 Endophthalmitis
Short View Summary
Categories
Acute Postoperative Endophthalmitis
Chronic Postcataract Endophthalmitis
Postinjection Endophthalmitis
Bleb-Related Endophthalmitis
Posttraumatic Endophthalmitis
Keratitis-Related Endophthalmitis
Endogenous Bacterial Endophthalmitis
Mycobacterial Endophthalmitis
Fungal Endophthalmitis
Endogenous Candida Endophthalmitis
Exogenous Candida Endophthalmitis
Mold Endophthalmitis
Diagnosis
Therapy
Acute Bacterial Endophthalmitis
Chronic Postcataract Endophthalmitis
Fungal Endophthalmitis
Endogenous Candida Endophthalmitis
Exogenous Candida Endophthalmitis
Mold Endophthalmitis
Visual Outcome
Preventing Endophthalmitis
Prophylaxis for Eye Surgery
Prophylaxis for Intravitreal Injections
Prophylaxis for Eye Trauma
Key References
References
115 Infectious Causes of Uveitis
Short View Summary
Epidemiology
Clinical Manifestations
Acute Retinal Necrosis
Brucellosis
Cat-Scratch Disease
Chikungungya Virus
Cytomegalovirus Anterior Uveitis
Cytomegalovirus Retinitis
Dengue
Ebola Virus
Herpetic Anterior Uveitis
Leprosy
Leptospirosis
Lyme Disease
Presumed Ocular Histoplasmosis Syndrome
Progressive Outer Retinal Necrosis
Syphilis
Ocular Toxocariasis
Toxoplasmosis
Tuberculosis
West Nile Virus
Whipple Disease
Zika Virus
Endophthalmitis Mimicking Uveitis
Chronic Postcataract Endophthalmitis
Chronic Endophthalmitis Due to Fungi
Diagnosis of Infectious Uveitis
Approach to the Patient With Uveitis
Therapy
Key References
References
116 Periocular Infections
Short View Summary
Eyelid Infections
Anatomy
Hordeolum
Chalazion
Blepharitis
Infections of the Lacrimal System
Anatomy
Dacryoadenitis
Canaliculitis
Dacryocystitis
Preseptal Cellulitis and Orbital Infections
Anatomy
Epidemiology
Etiology and Bacteriology
Clinical Manifestations
Preseptal and Orbital Cellulitis
Orbital and Subperiosteal Abscesses
Orbital Apex, Superior Orbital Fissure, and Cavernous Sinus Syndromes
Cavernous Sinus Thrombophlebitis
Laboratory and Radiologic Studies
Therapy
Key References
References
N Hepatitis
117 Viral Hepatitis
Short View Summary
Acute Viral Hepatitis
Clinical Manifestations
Laboratory Features
Prognosis of Acute Hepatitis
Fulminant Hepatitis
Complications of Acute Hepatitis
Agents of Viral Hepatitis
Hepatitis A Virus (Also See Chapter 174)
Hepatitis B Virus (Also See Chapter 145)
Hepatitis C Virus (Also See Chapter 154)
Hepatitis D Virus (Also See Chapter 146)
Hepatitis E Virus (Also See Chapter 178)
Diagnosis
Differential Diagnosis
Treatment
Prevention
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Chronic Viral Hepatitis
Chronic Hepatitis B
Distinctions Based on Relative Levels of Hepatitis B Virus Replication
Distinctions Based on Epidemiologic Considerations
Distinctions Based on Viral Variants
Pathophysiology and Natural History
Clinical Manifestations
Treatment
Interferon-Based Therapy for Chronic Hepatitis B
Direct Oral Antiviral Agents
Lamivudine.
Adefovir dipivoxil.
Entecavir.
Telbivudine.
Tenofovir.
Other Agents for Chronic Hepatitis B
Optimal Use of Available Agents for Hepatitis B
Recommendations for Therapy
Choice of Antiviral Agents
Special Patient Populations
Pregnancy
Liver Transplantation
HIV Coinfection (Also See Chapter 124)
Immune-Complex Disease
Oncology Patients Who Need Cytotoxic Chemotherapy
Chronic Hepatitis D
Treatment
Chronic Hepatitis C
Pathophysiology and Natural History
Clinical Manifestations
Hepatitis C Virus–HIV Coinfection (Also See Chapter 124)
Treatment
Pegylated Interferon and Ribavirin: Standard of Care 2001 to 2011— Treatment Principles Established
Tailored pegylated interferon and ribavirin therapy.
Clinical benefits of interferon-based therapy.
First-Generation NS3-4A Protease Inhibitors for Chronic Hepatitis C: Boceprevir and Telaprevir—Standard of Care for Genotype 1, 2011–13
Second-Generation NS3-4A Protease Inhibitor and First-Generation Nucleoside Polymerase Inhibitor for Chronic Hepatitis C: Simeprevir and Sofosbuvir—Standard of Care, 2014–15
First-Generation NS5A Inhibitors, Second-Generation Nucleoside Polymerase Inhibitors, and Third-Generation NS3-4A Protease Inhibitors—Standard of Care, 2015 to September 2017
Ledipasvir-sofosbuvir (Harvoni).
Ritonavir-booster paritaprevir, ombitasvir, and dasabuvir (Viekira Pak).
Elbasvir-Grazoprevir (Zepatier).
Daclatasvir (Daklinza).
Paritaprevir-ritonavir-ombitasvir (Technivie).
Second-Generation NS5A Inhibitors and Fourth-Generation NS3-4A Protease Inhibitors—Standard of Care, September 2017
Sofosbuvir-velpatasvir (Epclusa).
Sofosbuvir-velpatasvir-voxilaprevir (Vosevi).
Glecaprevir-pibrentasvir (Mavyret).
Considerations in Direct-Acting Antiviral Therapy of Chronic Hepatitis C
The role of resistance testing.
Reactivation of hepatitis B.
Does DAA cure increase the risk of HCC?
Candidates for Therapy
Challenge to Benefits of Direct-Acting Antiviral Therapy
Special Patient Populations
Liver Transplantation
HIV Coinfection (Also See Chapter 124)
Immune-Complex Disease
B-Cell Lymphoma
Other Special Populations
Chronic Hepatitis E
Treatment
Key References
References
O Acquired Immunodeficiency Syndrome
118 Global Perspectives on Human Immunodeficiency Virus Infection and Acquired Immunodeficiency Syndrome
Size of the Problem
Western Europe
Eastern Europe and Central Asia
Sub-Saharan Africa
Middle East and North Africa
Asia and the Pacific
Latin America and the Caribbean
Dynamics of the Spread of Human Immunodeficiency Virus
Modes of Transmission
Reducing the Spread of Human Immunodeficiency Virus
Safer Sexual Behavior
Male Circumcision
Preexposure Prophylaxis
Treatment as Prevention
Combination Prevention
Demography and Social Context
Gender
Stigma and Discrimination
Impact of Prevention and Care Programs
Impact of the AIDS Epidemic
Global Responses to AIDS
Key References
References
119 Epidemiology and Prevention of AIDS and HIV Infection, Including Preexposure Prophylaxis and HIV Vaccine Development
HIV and AIDS Surveillance in the United States
HIV Infection and AIDS in Adults
Incidence and Prevalence of AIDS and HIV in the United States (Also See Chapter 118 for Global Data)
Serologic Monitoring of the HIV Epidemic
Exposure Categories
AIDS Trends
Demographic Characteristics of HIV Infection
Geographic Distribution of HIV Infection
Clinical Manifestations of HIV Infection
Spectrum and Progression of HIV Infection
AIDS-Indicator Diseases
HIV Infection and Tuberculosis
Mortality of Persons With HIV Infections and AIDS
HIV/AIDS in Children
Modes of Transmission
Sexual Transmission
Infectiousness of the Source Partner
Susceptibility of the Recipient Partner
Transmission Through Injection Drug Use
Transmission by Blood and Other Tissues
Perinatal Transmission
Transmission of HIV in Health Care Settings
Other Modes of Transmission
HIV Infection and AIDS Outside the United States
HIV-2
Prevention of HIV Infection
Prevention of Sexual Transmission
Preexposure Prophylaxis
Prevention of Transmission by Injection Drug Use
Prevention of Transmission Through Blood and Other Tissues
Prevention of Transmission in the Health Care Setting
Prevention of Perinatal Infection
Counseling and HIV Antigen/Antibody Testing
Vaccines for HIV Type 1 Infection
Animal Models
Human Trials
Phase II Clinical Studies
Phase IIb and III Efficacy Studies
Broadly Neutralizing Antibodies Against HIV-1
Early Phase Clinical Trials
Summary
Key References
References
120 Diagnosis of Human Immunodeficiency Virus Infection
Short View Summary
Background/Perspective
Laboratory Advances
Implementation of HIV Diagnostics
Reporting HIV Infection
Terminology and Performance Characteristics
Specific Laboratory Methods for Detection of HIV Infection
Immune Responses to HIV
HIV Screening Assays
Serologic Techniques to Detect Anti-HIV Antibody
Standard ELISA Assays
Particle Agglutination Assays
Alternative ELISA Formats: Simple/Rapid Tests
Saliva as Source of Patient Material for ELISA Assay
Urine as Source of Patient Material for ELISA
Serologic Techniques to Screen for HIV Antigens
Fourth-Generation HIV Antigen-Antibody Assays
False-Positive and False-Negative Results in Screening Tests for HIV Antibody
Nonserologic Techniques to Screen for HIV
Hybridization and Amplification Assays to Detect HIV Nucleic Acids
HIV Supplemental and Confirmatory Assays
HIV-1/2 ELISA for Confirmation of HIV Infection
Western Blotting
Immunofluorescence
Virologic Techniques to Detect HIV Infection
Diagnostic Algorithms and Practical Application of HIV Detection Assays
HIV-1/2 Screening Phase
Acute HIV Infection
HIV-1/2 Supplemental Analysis
Test Counseling
Alternative Strategies for Screening/Confirmation HIV Detection
Specific Circumstances and Special Populations
HIV Diagnosis in Individuals Undergoing Preexposure Prophylaxis
Detection of HIV-2 and HIV-1/2 Dual Infections
Detecting Non-B HIV-1 Types and Subtypes Other Than Subtype B
Detecting HIV-1 Dual Infections
HIV Testing During Pregnancy or at Delivery
HIV in Perinatal Diagnosis
HIV Testing for Blood Donor Screening
HIV Testing in Tissue Procurement for Transplantation
HIV Testing in Vaccine, Prevention, Postexposure, and Gene Therapy Studies
HIV Testing in Gene Therapy Studies Using Lentiviral Vectors
HIV Infection but Viral RNA Less Than 50 Copies/mL: HIV Elite Controllers
HIV Testing in the Setting of Acute Retroviral Syndrome or Other Acute Illness
HIV Testing in Occupational Exposure
HIV Testing in Idiopathic CD4 Lymphopenia
Factitious HIV Infection and AIDS Phobia
HIV Testing to Estimate Duration of Infection and Incidence
Home Collection and Self-Testing for HIV
Other Human Retroviral Infections and New Retroviral Zoonoses
Regulatory Issues
Regulation of HIV Testing Modalities
Regulation of HIV Reporting
Conclusion
Acknowledgments
Key References
References
121 The Immunology of Human Immunodeficiency Virus Infection
HIV Entry and Dissemination
HIV Receptors and Entry Into Cells
Dissemination of HIV Infection
HIV-Specific Immune Responses
Humoral Immune Responses
Cellular Immune Responses
Cytotoxic T Lymphocytes
Soluble CD8+ T-Cell–Secreted Factors
CD4+ T-Cell Responses
Host Genetic Factors
Long-Term Nonprogressors/Elite Controllers
Host Immune Response Factors
Virologic Factors
Reservoirs of HIV Infection
Latent Reservoirs of HIV
Lymphoid Tissues
Strategies for HIV Eradication
Immune Dysfunction Caused by HIV Infection
Lymphoid Tissues
CD4+ T Cells
Mechanisms of CD4+ T-Cell Depletion
Increased Destruction
Direct infection.
Death by apoptosis and pyroptosis.
Lymphocyte turnover.
Decreased Production
Redistribution.
CD8+ T Cells
B Cells
Natural Killer Cells
Monocytes and Macrophages
Dendritic Cells
Role of Immune Activation in the Pathogenesis of HIV Infection
Cytokines and HIV Disease: Dysregulation of Cytokine Production
Role of Cytokines as Therapeutic Agents in HIV Infection
Conclusions
Key References
References
122 General Clinical Manifestations of Human Immunodeficiency Virus Infection (Including Acute Retroviral Syndrome and Oral, Cutaneous, Renal, Ocular, Metabolic, and Cardiac Diseases)
Short View Summary
History
Natural History of HIV Infection
Classification of HIV Infection
Clinical Manifestations
Effect of Antiretroviral Therapy on Natural History of HIV Infection
Acute Retroviral Syndrome
Persistent Generalized Lymphadenopathy
Constitutional Disease and Wasting
Metabolic and Endocrine Abnormalities
Oral Disease
Oral Candidiasis
Oral Hairy Leukoplakia
Gingivitis and Periodontitis
Oral Ulcers
Other Oral Lesions
Musculoskeletal Complications
Cutaneous Manifestations
Viral Infections of the Skin and Mucous Membranes
Bacillary Angiomatosis
Kaposi Sarcoma
Other Cutaneous Manifestations
Scabies
Renal Disease
Ocular Complications
Cardiac Manifestations
Hematologic Manifestations
Non–AIDS-Related Cancers
Immune Reconstitution Syndromes
Tuberculosis
Mycobacterium avium Complex Disease
Cytomegalovirus Disease
Infection With Varicella-Zoster Virus
Viral Hepatitis
Other Diseases
Key References
References
123 Pulmonary Manifestations of Human Immunodeficiency Virus Infection
Short View Summary
Epidemiology
Differential Diagnosis
Clinical or Laboratory Stage of Immunosuppression
Tempo of the Illness
Receipt and Type of Pneumocystis Prophylaxis
Receipt of Antiretroviral Therapy
History of Opportunistic Processes
Injection Drug Use and Smoking
Local Epidemiology or Past Residence
Characteristic Radiographic Findings
Triage of Patients: Infection Control Issues
Diagnostic Tests
Specific Pathogens
Pneumocystis Jirovecii Pneumonia
Bacterial Pneumonia
Mycobacterial Pneumonia
Fungal Pneumonia
Viral Pneumonia
Parasitic Pneumonia
Neoplastic and Other Noninfectious Pulmonary Complications of HIV Infection
Treatment
Key References
References
124 Gastrointestinal, Hepatobiliary, and Pancreatic Manifestations of Human Immunodeficiency Virus Infection
Short View Summary
Disorders of the Esophagus
Disorders of the Stomach
Disorders of the Biliary Tree and Gallbladder
Disorders of the Liver
Disorders of the Pancreas
Disorders of the Small and Large Intestine
Key References
References
125 Neurologic Diseases Caused by Human Immunodeficiency Virus Type 1 and Opportunistic Infections
Short View Summary
Principal Neurologic Manifestations of HIV Type 1 Infection
Meningeal Syndrome
Patient Otherwise Asymptomatic, CD4+ T-Lymphocyte Counts >200 Cells/µL: Aseptic Meningitis
Clinical presentation.
Laboratory investigations.
Treatment.
Patient at Any Stage of HIV-1 Infection and CD4+ T-Lymphocyte Counts at Any Level: Syphilitic Meningitis
Clinical presentation.
Laboratory investigations.
Treatment.
Patient With AIDS, CD4+ T-Lymphocyte Counts of <200 Cells/µL: Cryptococcal Meningitis
Clinical presentation.
Laboratory investigations.
Treatment.
Differential Diagnosis of Meningitis
Cognitive and Motor Syndromes
HIV Type 1–Associated Neurocognitive Disorder
Clinical presentation.
Laboratory investigations.
Imaging studies.
Brain biopsy and histologic analysis.
Treatment.
Central Nervous System Mass Lesions
Toxoplasma Encephalitis
Clinical presentation.
Laboratory investigations.
Imaging studies.
Brain biopsy.
Treatment.
Secondary prophylaxis.
Primary Central Nervous System Lymphoma
Clinical presentation.
Laboratory investigations.
Imaging studies.
Brain biopsy.
Treatment.
Progressive Multifocal Leukoencephalopathy
Clinical presentation.
Laboratory investigations.
Imaging studies.
Brain biopsy.
Treatment.
Inflammatory Progressive Multifocal Leukoencephalopathy
Cytomegalovirus Encephalitis
Clinical presentation.
Laboratory investigations.
Imaging studies.
Brain biopsy.
Treatment.
Miscellaneous Mass Lesions and Rationale for Brain Biopsy
Spinal Syndrome
Vacuolar Myelopathy
Clinical presentation.
Laboratory investigations.
Imaging studies.
Histologic studies.
Treatment.
Differential Diagnosis of a Noncompressive Myelopathy
Peripheral Nervous System Syndromes
HIV-Associated Neuropathies
Inflammatory Demyelinating Polyneuropathies
Laboratory investigations.
Electrophysiologic studies.
Nerve biopsy.
Treatment.
Distal Sensory Polyneuropathy
Clinical presentation.
Laboratory investigations.
Electrophysiologic studies.
Nerve and skin biopsy.
Treatment.
Nucleoside Neuropathy
Clinical presentation.
Laboratory investigations.
Treatment.
Mononeuritis Multiplex
Clinical presentation.
Laboratory investigations.
Electrophysiologic studies.
Nerve biopsy.
Treatment.
Progressive Polyradiculopathy
Clinical presentation.
Laboratory investigations.
Electrophysiologic studies.
Nerve biopsy.
Treatment.
Diffuse Infiltrative Lymphocytosis Syndrome–Associated Neuropathy
Clinical presentation.
Electrophysiologic studies.
Nerve biopsy.
Treatment.
Amyotrophic Lateral Sclerosis–Like Syndrome
Musculoskeletal Syndromes
HIV-Associated Myopathies
Muscular Complications From Therapies in HIV
Opportunistic Infections and Tumor Infiltrations
Seizures
Temporal Trends and Aging in Neurologic Manifestations of HIV Infection
Key References
References
126 Human Immunodeficiency Virus Infection in Women
Epidemiology
Epidemiology in the United States
Risk Factors for and Changing Patterns of Transmission
Racial and Ethnic Disparities in HIV Incidence
Age Patterns in Women Living With HIV in the United States
HIV Care Continuum Among Women
Worldwide Epidemiology
Disproportionate Impact on Young Women
Update on Perinatal Transmission Rates
Risk Factors for HIV Transmission to Women Worldwide
Regional Variation in HIV Incidence and the Impact on Women
AIDS-Related Mortality and Its Impact on Women and Families
Transmission and Acquisition in Women and Preventive Strategies
Heterosexual Transmission
Efficiency of Transmission
Factors Associated With Transmission
Impact of Hormonal Contraception on HIV Transmission and Acquisition
Sexually Transmitted Infections
HIV Infection Within the Genital Tract
Strategies to Prevent Heterosexual Transmission
Barrier Methods
Treatment of Sexually Transmitted Infections
Microbicides
Treatment as Prevention
Preexposure Prophylaxis in Women
Reproductive Care of Women Living With HIV
Conception for Women Living With or at Risk of HIV
Reproductive Desires
Fertility Issues
Safe Conception
Contraception for Women With or at Risk of HIV
Impact of Hormonal Contraceptives on HIV Progression
Drug-Drug Interactions Between ART and Hormonal Contraceptives
HIV and Pregnancy
Guidelines on Use of Antiretroviral Agents in Pregnant HIV-Infected Women
Perinatal Transmission: Timing, Risk Factors, and Strategies to Eliminate
Timing of Perinatal Transmission
Risk Factors for Perinatal Transmission
Use of Antiretroviral Drugs to Decrease Perinatal Transmission
Potential Mechanisms of Antiretroviral Drugs to Reduce Perinatal Transmission
Impact of Pregnancy on HIV Infection
Impact of HIV Infection on Pregnancy Outcomes
Antepartum Care of Women Living With HIV
HIV-Infected Pregnant Women Who Have Never Received Antiretroviral Drugs
HIV-Infected Pregnant Women Who Are Currently Receiving Antiretroviral Therapy
Stopping Antiretroviral Therapy During Pregnancy
HIV-Infected Pregnant Women Who Have Previously Received Antiretroviral Therapy but Are Not Currently Receiving Medication
Monitoring of the Woman and Fetus During Pregnancy
Teratogenicity
Intrapartum Antiretroviral Therapy
Care of Newborn
Postpartum Follow-Up of HIV-Infected Women
Clinical Manifestations of HIV Infection in Women
Opportunistic Processes and Nongynecologic Malignancies
Gynecologic Infections and Disease
Human Papillomavirus Infections
Cervical Infection
Extracervical Infection
Prevention of Human Papillomavirus Infection
Vaginal Infections
Bacterial Vaginosis
Vulvovaginal Candidiasis
Trichomonal Vaginitis
Pelvic Inflammatory Disease
Genital Ulcer Disease
Sex Differences in HIV Infection and Treatment Responses
Sex Differences in Clinical Progression
Virologic and Immunologic Differences Between Men and Women Off ART
Sex Differences in the HIV Reservoir and Possible Impact on Cure Strategies
Sex Differences in Responses to Antiretroviral Therapy and Pharmacokinetics
Treatment Outcomes
Pharmacokinetics
Sex Differences in Comorbidities
Sex Differences in Aging
Inclusion of Women in Clinical Research
Key References
References
127 Pediatric Human Immunodeficiency Virus Infection
Short View Summary
Current Epidemiology of Domestic Pediatric and Adolescent HIV Infection
Remaining Challenges in Domestic Pediatric HIV Infection
Elimination of New Pediatric HIV Infection
Maternal Determinants of Mother-to-Child Transmission
Postpartum Mother-to- Child Transmission
Elimination of Mother-to- Child Transmission
Management of the HIV-Exposed Infant
General Measures
Antiretroviral Agents
Diagnosis of HIV Infection in the HIV-Exposed Infant
Adolescent HIV Infection
Prevention of Infection
Issues in the Care of Aging HIV-Infected Youth
Disclosure of the HIV Diagnosis
Care Refusal and Low Adherence Among HIV-Infected Youth
Transition of HIV-Infected Youth From the Pediatric Care Model to the Adult Care Model
Adult Complications of Perinatal HIV Infection
Key References
References
128 Antiretroviral Therapy for Human Immunodeficiency Virus Infection
Short View Summary
Antiretroviral Agents
Nucleoside and Nucleotide Reverse-Transcriptase Inhibitors
Lamivudine-Emtricitabine
Abacavir
Tenofovir
Integrase Strand Transfer Inhibitors
Raltegravir
Elvitegravir
Dolutegravir
Bictegravir
Nonnucleoside Reverse-Transcriptase Inhibitors
Efavirenz
Rilpivirine
Protease Inhibitors
Boosted Atazanavir
Boosted Darunavir
Ritonavir
Drugs Used Less Commonly or of Historical Interest
Nucleoside and Nucleotide Reverse-Transcriptase Inhibitors (See Fig. 128.2)
Zidovudine
Stavudine
Didanosine
Nonnucleoside Reverse Transcriptase Inhibitors (See Fig. 128.4)
Nevirapine
Etravirine
Protease Inhibitors (See Fig. 128.5)
Saquinavir
Indinavir
Nelfinavir
Fosamprenavir
Lopinavir/Ritonavir
Tipranavir
Entry Inhibitors
Enfuvirtide
Maraviroc
Ibalizumab
Initiating Antiretroviral Therapy
When to Begin Therapy?
What to Begin With?
Dual-NRTI Backbone
Initial INSTI-, NNRTI-, or PI-Based Therapy
Initial Integrase Inhibitor–Based Therapy
Initial PI-Based Regimens
Alternative NNRTI-Based Regimens
Triple NRTI and Four-Drug Therapy
Two-Drug Therapy
Interrupting Therapy
Laboratory Testing During Antiretroviral Therapy
CD4 T-Cell Counts
HLA-B*5701 Screening
Plasma Viral Load Monitoring
HIV Drug Resistance Testing
Determining HIV Coreceptor Usage
Changing Therapy
Special Circumstances
Preexposure Prophylaxis
Postexposure Prophylaxis
Occupational HIV Exposures
Nonoccupational HIV Exposures
Conclusions and Future Directions
Key References
References
129 Management of Opportunistic Infections Associated With Human Immunodeficiency Virus Infection
Short View Summary
Immunologic Monitoring
Spectrum of Opportunistic Pathogens
Infections Due to Pathogens That Are Not Opportunistic
Management of Antiretroviral Therapy for Patients With Acute Opportunistic Infection
Drug Interactions
Prevention of Opportunistic Infections
Antiretroviral Therapy
Empirical Versus Specific Therapy
Management of Specific Opportunistic Infections
Pneumocystis jirovecii Pneumonia
Toxoplasma gondii
Herpes Simplex Virus and Varicella-Zoster Virus
Cytomegalovirus
Epstein-Barr Virus and Human Herpesvirus 6 and 7
JC Virus Encephalitis (Progressive Multifocal Leukoencephalopathy)
Candida Species
Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis/Coccidioides posadii
Bacterial Pneumonia
Mycobacterium Species Infection
Mycobacterium tuberculosis
Mycobacterium avium Complex
Enteric Pathogens: Salmonella, Shigella, and Campylobacter Species and Clostridiodes difficile (formerly Clostridium difficile)
Cryptosporidium, Cystoisospora, Cyclospora, and Microsporida Species
Treponema pallidum
Bartonella Species
Kaposi Sarcoma and Human Herpesvirus 8
Viral Hepatitis
Key References
References
P Miscellaneous Syndromes
130 Chronic Fatigue Syndrome (Systemic Exertion Intolerance Disease)
Short View Summary
History
Epidemiology
Etiology and Pathogenesis
Role of Infection
Role of the Autonomic Nervous System
Role of the Immune System
Role of the Central Nervous System
Role of the Genome
Clinical Manifestations
Laboratory Findings
Management
General Principles
Pharmacologic Therapy
Nonpharmacologic Therapy
Summary
Key References
References
III Infectious Diseases and Their Etiologic Agents
A Viral Diseases
131 Biology of Viruses and Viral Diseases
History
Virus Structure and Classification
Virus-Cell Interactions
Attachment
Penetration and Disassembly
Genome Replication
Release
Cell Killing
Antiviral Drugs
Virus-Host Interaction
Entry
Spread
Tropism
Persistent Infections
Viruses and Cancer
Viral Virulence Determinants
Host Responses to Infection
Key References
References
i DNA Viruses
a. Poxviridae
132 Orthopoxviruses Vaccinia (Smallpox Vaccine), Variola (Smallpox), Monkeypox, and Cowpox
Short View Summary
Background
Morphology and Chemical Structure
Pathogenesis
Vaccinia (Smallpox Vaccine)
Immunity Resulting From Vaccination
Complications Resulting From Vaccination
Vaccinia Virus as a Zoonosis
Variola (Smallpox)
Monkeypox
Pathogenesis
Clinical Manifestations
Diagnosis
Epidemiology and Control
Cowpox
Clinical Manifestations
Newly Described Orthopoxviruses
Orthopoxvirus Laboratory Diagnostics
Therapy
Key References
References
133 Other Poxviruses That Infect Humans: Parapoxviruses (Including Orf Virus), Molluscum Contagiosum, and Yatapoxviruses
Short View Summary
Parapoxviruses
Morphology and Composition of the Agent
Pathogenesis and Immune Response
Clinical Manifestations
Diagnosis
Epidemiology
Therapy
Molluscum Contagiosum
Description of the Agent
Pathogenesis and Pathology
Clinical Manifestations
Diagnosis
Epidemiology and Control
Therapy
Yatapoxviruses
Tanapox
Pathophysiology and Clinical Manifestations
Diagnosis
Epidemiology and Control
Yaba Monkey Tumor Virus
Clinical Manifestations
Key References
References
b. Herpesviridae
134 Introduction to Herpesviridae
Classification
Genome Structure and Proteins
Virus Replication
Virus Latency and Reactivation
Pathogenesis
Epidemiology
Clinical Syndromes
Immunity
Oncogenesis
Diagnosis
Therapy
Prevention
Key References
References
135 Herpes Simplex Virus
Short View Summary
Description of Virus
Microbiology Virus Structure
Virus Replication
Molecular Features of Latency
Dynamics of Herpes Simplex Virus Latency and Reactivation
Epidemiology
Herpes Simplex Virus Type 1
Herpes Simplex Virus Type 2
Herpes Simplex Virus Type 2 Risk Factors
Transmission
Pathogenesis
Primary Infection
Ganglionic Cell–Mediated Immunity
Mucosal Cell–Mediated Immunity
Innate Host Factors Impacting Pathogenesis and Disease Severity
Cell-Mediated Host Factors Impacting Pathogenesis and Disease Severity
Humoral Host Factors Impacting Pathogenesis and Disease Severity
Spectrum of Diseases Caused by Herpes Simplex Virus
Orofacial Herpes Simplex Virus Infection
Complications of Oral Herpes Simplex Virus Type 1
Genital Herpes Simplex Virus Infection
Local Complications of Genital Herpes Simplex Virus Infection
Aseptic Meningitis, Transverse Myelitis, and Sacral Radiculopathy
Extragenital Lesions
Disseminated Infection
Superinfection
Recurrent Mucocutaneous Herpes Simplex Virus Infections
Frequency of Reactivation and Recurrence
Subclinical Herpes Simplex Virus Type 2 Shedding
Herpetic Whitlow
Herpes Gladiatorum
Eye Infections
Herpes Simplex Virus Encephalitis
Visceral and Pulmonary Herpes Simplex Virus Infections
Genital Herpes Simplex Virus Infection in HIV-Infected Patients
Increased Risk of HIV-1 Acquisition in Herpes Simplex Virus Type 2–Infected Patients
Impact of Herpes Simplex Virus Type 2 Infection on HIV Transmission Probability From Coinfected Patients
Herpes Simplex Virus Infections in Immunocompromised Hosts Not Infected With HIV
Neonatal Herpes
Prevention Measures for Neonatal Herpes
Herpes Simplex Virus Infection in Pregnancy
Clinical Course of Genital Herpes in Pregnancy
Surveillance Strategies for Neonatal Transmission of Herpes Simplex Virus
Prevention of Herpes Simplex Virus Acquisition in Pregnancy by Use of Antiviral Agents
Diagnosis of Active Herpes Simplex Virus Infections
Diagnosis of Established Herpes Simplex Virus Infections
Overview of Therapies for Herpes Simplex Virus Infections
Treatment of Primary Genital Herpes Simplex Virus Infection
Suppressive Therapy for Persistent Genital Herpes Simplex Virus Infection
Episodic Therapy for Persistent Genital Herpes Simplex Virus Infection
Therapy for Severe Herpes Simplex Virus Infection
Prophylaxis of Herpes Simplex Virus in Immunocompromised Hosts and Development of Drug Resistance
Treatment of Drug-Resistant Herpes Simplex Virus
Novel Antiviral Agents for Herpes Simplex Virus Type 1 and Type 2 Infections
Counseling and Prevention
Herpes Simplex Virus Vaccines
Key References
References
136 Chickenpox and Herpes Zoster (Varicella-Zoster Virus)
Short View Summary
Historical Overview
Pathogen and Its Replication
Epidemiology of Varicella-Zoster Virus Infections
Chickenpox
Herpes Zoster
Pathogenesis
Clinical Manifestations
Chickenpox
Chickenpox in the Immunocompromised Patient
Herpes Zoster
Diagnosis
Therapy
Prevention
Key References
References
137 Cytomegalovirus
Short View Summary
Microbiology
Virus Structure
Replication
Persistence in the Host
Host Interaction and Responses
Pathogenesis of HCMV Infection
Pathogenesis of HCMV in the Setting of Immunosuppression and Virus Dissemination
Pathogenesis of Diseases That Lack a Direct Relationship to Levels of Virus Replication
Routes of Transmission and Sources of HCMV Infection
Clinical Manifestations
Infection in the Immunocompetent Host (Infectious Mononucleosis)
Transfusion-Acquired Infection
Association With Inflammatory Bowel Disease
HCMV Infections in the Immunocompromised Host
HCMV Infections in Solid-Organ Transplant Recipients (See Also Chapter 308)
HCMV Infection and Allograft Survival and Function in Solid-Organ Transplantation
HCMV Infections in Hematopoietic Stem Cell Transplant Recipients (See Also Chapter 307)
Congenital HCMV Infection
Diagnosis of HCMV Infections
Quantitative Nucleic Acid Amplification Technologies
Antigen Detection
Virus Culture
Serology
Diagnosis of Congenital Infections
Therapy of HCMV Infections (see also Chapter 46)
Prophylaxis and Preemption
Viral Resistance
Therapy of Congenital Infections
Passive Immunotherapies for the Prevention and Treatment of HCMV Infections
Vaccines for the Prevention and Treatment of HCMV Infections
Key References
References
138 Epstein-Barr Virus (Infectious Mononucleosis, Epstein-Barr Virus–Associated Malignant Diseases, and Other Diseases)
Short View Summary
History
Description of Epstein-barr Virus
Physical Properties
Life Cycle
Latent Infection and Growth Transformation
Epstein-Barr Virus Drives B Cells to Proliferate
Epstein-Barr Virus Genome Is Circularized in Latent Infection and Expresses a Subset of Viral Genes
Functions of Epstein-Barr Virus Genes Expressed in Latent Infection
Patterns of Epstein-Barr Virus Gene Expression Vary in Different Malignancies
Lytic Infection
Epidemiology
Serum Antibody Prevalence
Incidence of Infection
Methods of Spread
Public Health Impact
Pathogenesis
Host Immune Response
Immune Response Controls Epstein-Barr Virus Infection and Is the Cause of Mononucleosis Symptoms
Cellular Response to Epstein-Barr Virus
Humoral Response to Epstein-Barr Virus
Heterophile Antibodies Generated Early During Primary Epstein-Barr Virus Infection Have No Known Role in Pathogenesis
Epstein-Barr Virus Immune Evasion
Histopathologic Findings
Clinical Manifestations
Infectious Mononucleosis (Primary Infection)
Spectrum of Illness
Symptoms and Signs
Complications
Dermatologic Complications
Hematologic Complications
Splenic Rupture
Neurologic Manifestations
Hepatic Manifestations
Renal Manifestations
Cardiac Manifestations
Pulmonary Manifestations
Death
Clinical Course
Genetic Disorders Associated With Severe Epstein-Barr Virus Disease
X-linked Genetic Predispositions to Severe Epstein-Barr Virus Disease
Autosomal Genetic Predispositions to Severe Epstein-Barr Virus Disease
Genetic Disorders That Predispose to Severe Epstein-Barr Virus Disease and Other Infections
Chronic Active Epstein-Barr Virus Infection
Epstein-Barr Virus–Associated Hemophagocytic Lymphohistiocytosis
Oral Hairy Leukoplakia
Epstein-Barr Virus–Associated Malignant Diseases
Lymphoproliferative Disease
Burkitt Lymphoma
Hodgkin Lymphoma
Diffuse Large B-Cell Lymphoma
Nasopharyngeal Carcinoma
Gastric Carcinoma
Other Malignant Diseases
Multiple Sclerosis and Other Autoimmune Diseases
Laboratory Diagnosis
Infectious Mononucleosis
Hematologic Findings
Heterophile Antibodies
Epstein-Barr Virus–Specific Antibodies
Viral Capsid Antigen Antibodies
Early Antigen Antibodies
Epstein-Barr Nuclear Antigen Antibodies
Culture of Epstein-Barr Virus
Epstein-Barr Virus Viral Load
Other Laboratory Abnormalities
Posttransplant Lymphoproliferative Disease
Nasopharyngeal Carcinoma
Central Nervous System Lymphoma in Acquired Immunodeficiency Syndrome
Differential Diagnosis of Infectious Mononucleosis
Heterophile-Negative Infectious Mononucleosis Caused by Epstein-Barr Virus
Cytomegalovirus as a Cause of Heterophile-Negative Infectious Mononucleosis
Primary Human Immunodeficiency Virus Infection
Group A Streptococcal Pharyngitis
Hepatitis A, B, or C
Toxoplasmosis and Other Infections
Therapy
Infectious Mononucleosis
Supportive
Antiviral Agents
Corticosteroids
Lymphoproliferative Disease
Epstein-Barr Virus Targeted Therapy in Associated Malignant Diseases
Oral Hairy Leukoplakia
Prevention
Public Health Measures
Vaccine
Key References
References
139 Human Herpesvirus Types 6 and 7 (Exanthem Subitum)
Short View Summary
Human Herpesvirus Type 6
History
Description of the Virus
Epidemiology
Pathogenesis
Clinical Manifestations
Infantile Fever and Seizures
Exanthem Subitum (Roseola Infantum or Sixth Disease)
Other Neurologic Symptoms Associated With HHV-6
Infectious Mononucleosis
Other Complications in Healthy Persons
Congenital Infection
Infection in the Immunocompromised Host
Laboratory Diagnosis
Healthy Persons
Immunocompromised Persons
Therapy
Human Herpesvirus Type 7
History
Description of the Virus
Epidemiology
Pathogenesis
Clinical Manifestations
Laboratory Diagnosis
Therapy
Key References
References
140 Kaposi Sarcoma–Associated Herpesvirus (Human Herpesvirus 8)
Short View Summary
History
Discovery of KSHV
Classification and Biology
Virus Description
KSHV Entry Into Cells
Lytic Virus Infection
Latent Virus Infection
KSHV Gene Expression in Latent Infection
Possible Paracrine Effects of Lytic Virus Infection
Laboratory Infection Models
Pathogenesis
Suppression of Immunity as a Factor Leading to KSHV Malignancy
KSHV and Inflammation
Epidemiology
Assays to Identify KSHV Infection
Geographic Variance of KSHV Seroprevalence in Contrast to Other Herpesviruses
KSHV Transmission
Clinical Manifestations
Primary Infection
Kaposi Sarcoma
Four Epidemiologic Forms of KS
Diagnosis
KSHV Viral Load Measurement
Genetic Predisposition to KS
Treatment
KS-Associated IRIS After Institution of Antiretroviral Therapy
Primary Effusion Lymphoma
Multicentric Castleman Disease
KSHV Inflammatory Cytokine Syndrome
Other Syndromes
Therapy and Prevention
Key References
References
141 Herpes B Virus
Short View Summary
History
Description of the Virus
Epidemiology
Pathogenesis
Clinical Manifestations
Laboratory Diagnosis After Exposure
Postexposure Evaluation and Prophylaxis
Diagnosis of Herpes B Virus Disease
Therapy
Prevention
Key References
References
c. Adenoviridae
142 Adenoviruses
Short View Summary
Description of the Pathogen
Interactions With the Host
Epidemiology
Clinical Syndromes
Respiratory Tract Disease
Ocular Disease
Gastrointestinal Tract Disease
Genitourinary Tract Disease
Central Nervous System Disease
Other Clinical Syndromes
Infections in Immunocompromised Patients
Hematopoietic Stem Cell Transplant Recipients
Solid-Organ Transplant Recipients
Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients
Diagnosis
Therapy
Prevention
Adenoviruses as Vectors for Gene Therapy and Vaccination
Key References
References
d. Papillomaviridae
143 Papillomaviruses
Short View Summary
Virology
Epidemiology
Incidence and Prevalence
Transmission
Association Between Human Papillomavirus and Malignant Diseases
Pathogenesis
Clinical Manifestations
Cutaneous Warts
Epidermodysplasia Verruciformis
Anogenital Warts
Recurrent Respiratory Papillomatosis
Other Human Papillomavirus Infections
Diagnosis
Therapy
Cutaneous Warts
Anogenital Warts
Other Warts
Prevention and Vaccination
Vaccination
Key References
References
144 JC, BK, and Other Polyomaviruses: Progressive Multifocal Leukoencephalopathy (PML)
Short View Summary
Virology
History
Epidemiology
Genome
Receptors and Cell Entry
JC Virus
BK Virus
New Human Polyomaviruses
Progressive Multifocal Leukoencephalopathy and Other JC Virus–Associated Syndromes
Epidemiology
Pathogenesis
Clinical Manifestations
Classic Progressive Multifocal Leukoencephalopathy
Progressive Multifocal Leukoencephalopathy–Immune Reconstitution Inflammatory Syndrome
JC Virus Granule Cell Neuronopathy
JC Virus Encephalopathy
JC Virus Meningitis
Diagnosis
Imaging
Brain Biopsy
Cerebrospinal Fluid Polymerase Chain Reaction Assay
Prognosis
Therapy
Nephropathy and Other BK Virus–Associated Diseases
Epidemiology
Pathogenesis
Clinical Manifestations
Nephropathy
Ureteral Stenosis
Hemorrhagic Cystitis
Infections Outside the Renal System
Diagnosis
Urine Polymerase Chain Reaction Assay
Renal Biopsy
Plasma Polymerase Chain Reaction Assay
Prognosis
Prevention and Therapy
Nephropathy
Ureteral Stenosis
Hemorrhagic Cystitis
Key References
References
e. Hepadnaviridae
145 Hepatitis B Virus
Short View Summary
Overview
Historical Background and Classification
Virology
Attachment, Entry, and Hepatotropism
Viral Genome
Transcription
Translation
Replication
HBx
Morphogenesis and Assembly
Natural History and Pathogenesis of Disease
Natural History
Pathogenesis
Acute Hepatitis B
Chronic Hepatitis B
Hepatocellular Carcinoma
Epidemiology of Hepatitis B
Routes of Transmission
Clinical Manifestations and Prognosis
Acute Hepatitis B
Fulminant Hepatitis
Chronic Hepatitis B
Precore or HBe-Negative Mutants
Prognosis of Untreated Chronic Hepatitis B
Hepatocellular Carcinoma
Extrahepatic Manifestations of Hepatitis B
Clinical Manifestations and Natural History in Special Hosts
Individuals With Human Immunodeficiency Virus Infection
Hepatitis B After Liver Transplantation
Hepatitis B After Other Types of Transplantation
Coinfection With Hepatitis C
Screening and Diagnosis of HBV Infection
Acute Hepatitis
Past Hepatitis B Infection and Vaccination
Chronic Hepatitis B Infection
Measures of Hepatitis B Replication
Isolated anti-HBc
Management of Hepatitis B
Chronic Hepatitis B
Acute Hepatitis B
Selection of Patients for Treatment
Interferon
Nucleoside and Nucleotide Analogues
Lamivudine
Adefovir
Entecavir
Telbivudine
Tenofovir Disoproxil Fumarate (TDF) and Tenofovir Alafenamide (TAF)
Other Agents and Combination Therapy
Viral Resistance
Monitoring and Treatment Duration of Nucleos(t)ide Therapy
Management in Special Populations
Liver Transplantation
Human Immunodeficiency Virus
Recipients of Immunosuppressive Therapies
Treatment of Hepatitis B Virus During Pregnancy
Other Management Issues in Chronic Hepatitis B
Hepatitis A Vaccination
Screening and Vaccination of Contacts
Surveillance for Hepatocellular Carcinoma
Prevention of Hepatitis B Virus Infection
Active Immunization
Indications for Vaccination
Dose Regimen
Efficacy
Efficacy in Patients With Human Immunodeficiency Virus Infection
Efficacy in End-Stage Renal Disease
Durability of Response
Postexposure Immunoprophylaxis
Prevention of Perinatal Transmission
Hepatitis B Surface Antigen Escape Mutants
Acknowledgments
Key References
References
146 Hepatitis Delta Virus
Short View Summary
Hepatitis Delta Virus
Hepatitis Delta Antigen
Hepatitis D Virus Life Cycle
Hepatocyte Entry
RNA Genome and Replication
Pathogenesis
Epidemiology
Diagnosis
Transmission and Clinical Manifestations
Treatment
Transplantation
Key References
References
f. Parvoviridae
147 Human Parvoviruses, Including Parvovirus B19V and Human Bocaparvoviruses
Short View Summary
Parvovirus B19
Virology
Pathogenesis
Epidemiology
Prevalence and Incidence
Mechanism and Routes of Transmission
Clinical Manifestations
Erythema Infectiosum
Arthropathy
Transient Aplastic Crisis
Pure Red Cell Aplasia
Virus-Associated Hemophagocytic Syndrome
Fetal Infection (Hydrops Fetalis and Miscarriage)
Other Disease Manifestations
Immune Response
Diagnosis
Therapy
Prevention and Vaccination
Other Human Parvoviruses
Human Dependoparvoviruses
Human Bocaparvoviruses
Parv4
Human Protoparvoviruses
Key References
References
ii. RNA Viruses •
a. Reoviridae
148 Orthoreoviruses and Orbiviruses
Short View Summary
Orthoreoviruses
Background and Epidemiology
Clinical Disease
Respiratory Tract Manifestations
Gastrointestinal and Hepatobiliary Manifestations
Central Nervous System Manifestations
Reovirus as an Oncolytic Agent
Orbiviruses
Background and Epidemiology
Clinical Disease
Clinical Manifestations of Specific Agents
Kemerovo Virus Antigenic Complex
Oklahoma Tick Fever
Orungo Virus
Lebombo Virus
Changuinola Virus
African Horse Sickness Virus
Diagnosis
Key References
References
149 Coltiviruses (Colorado Tick Fever Virus) and Seadornaviruses
Short View Summary
Coltiviruses
Colorado Tick Fever Virus
Epidemiology
Clinical and Laboratory Features
Diagnosis
Treatment and Prevention
Salmon River Virus
Eyach Virus
Seadornaviruses
Banna Virus
Acknowledgment
References
150 Rotaviruses
Short View Summary
History and Overview
Classification and Impact
Discovery
Path From Basic Science to Vaccine Introduction
Viral Structure and Replication
Structural Overview
Inactivation
Priming for Infectivity
Receptor Binding and Human Susceptibility
Internalization Into Target Cells
Conformational Changes Linked to Membrane Perforation and Escape
Transcription From Double-Layered Particles and Preferential Translation of Viral mRNA
Genome Packaging and Assortment
Viroplasm Formation
Reverse Genetics Systems
Outer Capsid Assembly
Clinical Manifestations
Typical Clinical Illness
Clinical Laboratory Findings
Spectrum of Disease Severity
Extraintestinal Manifestations and Disease in Immunodeficiency
Other Disease Associations
Proposed Links to Autoimmunity
Pathogenesis
Pathologic Findings in Infection
Human Intestinal Enteroid Infection Model
Correlations Between Pathologic and Clinical Findings
Physiology of Rotavirus Diarrhea
Viral Enterotoxin
The Enteric Nervous System in Rotavirus Gastroenteritis
Serology and Classification
Overview
Rotavirus Groups
Binomial Serology of Group A Rotaviruses
Genetic Classification of Group A Strains
Diversity of Group A Strains
Epidemiology
Universality of Infection
Mortality and Global Impact
Health Care Utilization and Impact in High-Income Countries
Seasonality
Transmission
Risk Factors for Disease
Veterinary and Zoonotic Disease
Immunity
Protection From Reinfection by Natural Infection
Protection by Antibody
Protection by Breastfeeding
Role of Serotype in Protection
Heterotypic Neutralization by Antibodies
Mechanisms of Neutralization by Antibodies
Protection by Antibodies Against VP6 and Intracellular Neutralization
Mouse Studies on the Roles of T-Cell–Mediated, Antibody-Mediated, and Innate Immunity in Viral Clearance and Protection From Reinfection
Evidence for the Role of Innate Immunity From Studies in Human Cells
Diagnosis
Clinical Utility of Virologic Diagnosis
Diagnosis by Antigen Detection
Diagnosis by Reverse-Transcriptase Polymerase Chain Reaction
Diagnosis by Electron Microscopy, Electrophoresis, and Viral Culture
Future Diagnostic Trends
Therapy
Overview
Rehydration
Zinc Supplementation
Antidiarrheal Agents
Antiemetics
Probiotics
Passive Oral Immunotherapy and Immunoprophylaxis
Immunization
Overview
RotaShield and History of Intestinal Intussusception
Rotarix
RotaTeq
Contraindications for Allergic Reactions, Severe Combined Immunodeficiency Disease, and Elevated Risk of Intestinal Intussusception
Porcine Circovirus in Vaccine Manufacturing
Reduction in Rotavirus Disease Burden Resulting From Immunization
Reduced Vaccine Efficacy in Low-Income Settings
Benefits of Rotavirus Immunization in Low-Income Settings
Global Rotavirus Vaccine Introduction
Regional Rotavirus Vaccines: Lanzhou Lamb Rotavirus Vaccine, Rotavac, Rotasiil, and Rotavin-M1
Nonreplicating Rotavirus Vaccine Candidates
Acknowledgments
Key References
References
b. Togaviridae
151 Alphaviruses (Chikungunya, Eastern Equine Encephalitis)
Short View Summary
History
Mechanism of Replication
Phylogeny
Epidemiology
Encephalitis-Causing Alphaviruses
Eastern Equine Encephalitis Viruses
Western Equine Encephalitis Viruses
Venezuelan Equine Encephalitis Viruses
Alphaviruses Causing Fever, Polyarthritis, and Rash
Chikungunya Virus
O’nyong-Nyong Virus
Sindbis Virus
Ross River Virus and Barmah Forest Virus
Mayaro Virus
Pathogenesis
Encephalitis
Fever, Arthralgia, and Rash
Clinical Manifestations
Alphaviruses Causing Encephalitis
Alphaviruses Causing Fever, Polyarthritis, and Rash
Diagnosis
Therapy and Prevention
Key References
References
152 Rubella Virus (German Measles)
Short View Summary
Epidemiology
Transmission of Rubella
Maintenance of Immunity to Rubella
Pathogenesis
Clinical Manifestations
Postnatal Rubella
Complications of Postnatal Rubella
Congenital Rubella Syndrome
Diagnosis
Therapy
Vaccination Against Rubella
Complications of Vaccination
Efficacy of Vaccination
Effects of Rubella Vaccine on the Fetus
Key References
References
c. Flaviviridae
153 Flaviviruses (Dengue, Yellow Fever, Japanese Encephalitis, West Nile Encephalitis, Usutu Encephalitis, St. Louis Encephalitis, Tick-Borne Encephalitis, Kyasanur Forest Disease, Alkhurma Hemorrhagic Fever, Zika)
Short View Summary
History
Yellow Fever
Dengue
Japanese Encephalitis Virus
West Nile Virus
Usutu Virus
St. Louis Encephalitis Virus
Tick-Borne Encephalitis Virus
Alkhurma Hemorrhagic Fever Virus
Kyasanur Forest Disease Virus
Zika Virus
Pathogens
Epidemiology
Yellow Fever
Dengue
Japanese Encephalitis
West Nile Encephalitis
St. Louis Encephalitis
Tick-Borne Encephalitis
Alkhurma Hemorrhagic Fever
Kyasanur Forest Disease
Zika
Pathogenesis
Yellow Fever
Dengue and Dengue Hemorrhagic Fever
Encephalitis
Congenital Malformations and Guillain-Barré Syndrome
Clinical Manifestations
Yellow Fever
Dengue Fever and Dengue Hemorrhagic Fever
Japanese Encephalitis
West Nile Virus Fever and West Nile Encephalitis
St. Louis Encephalitis
Tick-Borne Encephalitis (Including Powassan Encephalitis)
Alkhurma Hemorrhagic Fever
Kyasanur Forest Disease
Zika Virus Infection
Laboratory Diagnosis
Prevention and Therapy
Yellow Fever
Dengue and Dengue Hemorrhagic Fever
Zika Virus Infection
Flavivirus Encephalitis
Other Flavivirus Infections
Murray Valley Encephalitis
Rocio Encephalitis
Omsk Hemorrhagic Fever
Less Commonly Recognized Flavivirus Infections
Acknowledgments
Key References
References
154 Hepatitis C
Short View Summary
Non-a, Non-B Viral Hepatitis and Hepatitis C
Hepatitis C Virus
Virology and Classification
Organization of the Hepatitis C Virus Genome
Nontranslated RNA Segments
Polyprotein
Structural Proteins
p7 and NS2 Proteins
Nonstructural Proteins Involved in RNA Replication
Viral Replication
Genetic Diversity
Quasispecies Variation
Hepatitis C Virus Genotypes
Viral Tropism
Experimental Models
Autonomously Replicating Viral Replicons and Genome-Length RNAs
Propagation of Virus in Cell Cultures
Animal Models
Natural History and Pathogenesis
Viral Persistence
Innate Immunity
Humoral Immunity
Cellular Immunity
Disease Progression
Hepatic Fibrosis
Human Immunodeficiency Virus and Hepatitis C Virus Infection
Clinical Manifestations of Hepatitis C Virus Infection
Acute Hepatitis C
Fulminant Hepatitis C
Chronic Hepatitis C
Hepatocellular Carcinoma
Extrahepatic Manifestations of Hepatitis C Virus Infection
Diagnosis Laboratory Assessment of Hepatitis C Virus Infection
Screening Serology
RNA Detection
Core Antigen Detection
Genotype
Other Laboratory Testing
Clinical Application of Tests for Hepatitis C Virus
Liver Fibrosis Staging
Liver Biopsy
Noninvasive Blood Markers of Hepatic Fibrosis
Radiographic Tests
Approach to Staging Liver Disease
Epidemiology of Hepatitis C
Prevalence of Hepatitis C Virus
Prevalence of Hepatitis C Virus in Those With HIV
Incidence and Transmission of Hepatitis C Virus
Biologic Basis of Transmission
Percutaneous Transmission
Nosocomial Infection
Sexual Transmission
Maternal-Infant Transmission
Transmission Cofactors
Treatment of Chronic Hepatitis C
Treatment Responses
Virologic Responses
Histologic and Clinical Responses to Therapy
Medications
Interferon-α
Ribavirin
Protease Inhibitors
Nucleos(t)ide and Nonnucleoside Polymerase Inhibitors
NS5A Protein Inhibitors
Treatment of Chronic Hepatitis C
History and Progress (Fig. 154.9)
Initial Treatment of Chronic Hepatitis C Virus Infection
Genotype 1
Genotype 2
Genotype 3
Genotype 4
Genotypes 5 and 6
Response Indicators
Antiviral Resistance
Re-treatment of Chronic Hepatitis C Virus Infection
Failure of Interferon and Ribavirin With or Without NS3/4 Protease Inhibitor
Failure of Non-NS5A Inhibitor, Sofosbuvir-Containing Regimens
Failure of Direct-Acting Antiviral Regimens Containing NS5A Inhibitors
Adverse Reactions
Recommended Treatments for Chronic Hepatitis C as of 2018
Selection of Patients for Treatment
Initial Treatment and Re-treatment of Patients With Chronic Hepatitis C, Including Those With HIV Infection
Treatment of Acute Hepatitis C
Prevention
Preexposure Prevention
Postexposure Prevention
Hepatitis C Virus Elimination
World Health Organization Goals
Current State: Hepatitis C Virus Treatment Cascade
From Modeling to Real-World Examples
Acknowledgments
Key References
References
d. Coronaviridae
155 Coronaviruses, Including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)
Short View Summary
History
Community-Acquired Respiratory Coronaviruses, Severe Acute Respiratory Syndrome, and Middle East Respiratory Syndrome
Gastrointestinal Coronaviruses and Toroviruses
Description of the Pathogens
Epidemiology
CAR Coronaviruses
MERS Coronavirus
SARS Coronavirus
Gastrointestinal Coronaviruses
Pathogenesis
CAR Coronaviruses
MERS Coronavirus
SARS Coronavirus
Clinical Manifestations
CAR Coronaviruses
MERS Coronavirus
SARS Coronavirus
Gastrointestinal Coronaviruses
Neurologic Syndromes
Laboratory Diagnosis
CAR Coronaviruses
MERS Coronavirus
SARS Coronavirus
Therapy
Prevention
Key References
References
e. Paramyxoviridae
156 Parainfluenza Viruses
Short View Summary
Virology
Pathogenesis
Epidemiology
Clinical Manifestations
Pediatric Disease
Adult Disease
Parainfluenza Virus in Immunocompromised Patients
Diagnosis
Therapy
Prevention
Key References
References
157 Mumps Virus
Short View Summary
History
Virology
Epidemiology
Pathogenesis
Pathology
Clinical Manifestations
Complications
Immunology
Diagnosis
Differential Diagnosis
Therapy
Prevention
Key References
References
158 Respiratory Syncytial Virus
Short View Summary
History
Virology
Classification
Viral Structure and Characteristics
Laboratory Properties
Infection in Animals
Epidemiology
Distribution and Seasonal Occurrence
Antigenic Variation
Epidemiology Manifestations
Prevalence and Incidence
Pathogenesis
Immunity and Pathogenesis of Disease
Maternally Derived Immunity
Innate Immunity
Adaptive Immunity
Clinical Manifestations
Infection Among Young Children (Bronchiolitis and Other Lower Respiratory Tract Illnesses)
Otitis Media
Infections Among Older Children
Infections Among Adults
Complications
Patients at High Risk for Severe Infection
Immunocompromised Patients
Acute Complications in Infants
Long-Term Complications
Diagnosis
Therapy
Prevention
Infection Prevention
Prophylaxis
Immunization
Acknowledgments
Key References
References
159 Human Metapneumovirus
Short View Summary
Virology
Pathogenesis and Host Response
Epidemiology
Clinical Manifestations
Children
Adults
Immunocompromised Hosts
Diagnosis
Viral Culture
Immunofluorescence Assay
Reverse-Transcriptase Polymerase Chain Reaction
Serology
Treatment
Prevention
Key References
References
160 Measles Virus (Rubeola)
Short View Summary
Description of the Pathogen
Morphology
Chemical and Antigenic Composition
Growth of Measles Virus in Tissue Culture
Host Range
Epidemiology
Spread of Infection
Other Diseases Associated With Measles Virus
Pathogenesis
Immunity
Clinical Manifestations
Complications
Special Considerations
Modified Measles
Atypical Measles
Immunocompromised Patients
Pregnant Women and Their Offspring
Persons With Tuberculosis
Occurrence in Adults
Diagnosis
Prevention
Therapy
Key References
References
161 Zoonotic Paramyxoviruses
Short View Summary
Virology
Classification
Structure and Molecular Biology
Nipah and Hendra Viruses
Menangle Virus
Emergence of Henipaviruses
Nipah Virus
Epidemiology
Reservoirs and Intermediate Hosts
Clinical Manifestations
Laboratory Abnormalities
Diagnostic Tests
Pathology
Therapy
Prevention
Hendra Virus
Epidemiology
Reservoirs and Intermediate Hosts
Clinical Manifestations
Laboratory Abnormalities
Diagnostic Tests
Pathology
Therapy
Prevention
Menangle Virus
Epidemiology
Pathogenesis
Clinical Manifestations and Diagnostic Tests
Key References
References
f. Rhabdoviridae
162 Vesicular Stomatitis Virus and Related Vesiculoviruses (Chandipura Virus)
Short View Summary
Virology
Classification and Structure
Molecular Biology
Epidemiology
Epizootic
Enzootic
Animal Disease
Clinical Manifestations
Diagnosis
Host Response
Therapy
Prevention and Vaccination
Key References
References
163 Rabies (Rhabdoviruses)
Short View Summary
Virology
Classification
Epidemiology
Human Rabies
Transplant-Associated Rabies
Animal Rabies
Composition
Pathogenesis
Pathology
Immune Responses
Clinical Manifestations
Human Rabies
Incubation Period
Prodromal Symptoms
Encephalitic (Furious) Rabies
Paralytic (Dumb) Rabies
Nonneurologic Findings
Animal Rabies
Diagnosis
Differential Diagnosis
Prevention
Preexposure Prophylaxis
Postexposure Prophylaxis
Treatment
Key References
References
g. Filoviridae
164 Marburg and Ebola Virus Hemorrhagic Fevers
Short View Summary
Virus Characterization
Epidemiology
Marburg Hemorrhagic Fever
Ebola Hemorrhagic Fever
Natural History
Clinical Manifestations and Diagnosis
Pathogenesis
Countermeasures
Prevention
Treatment
Key References
References
h. Orthomyxoviridae
165 Influenza Viruses, Including Avian Influenza and Swine Influenza
Short View Summary
History
The Viruses
Classification
Virology
Epidemiology and Disease Impact
Disease Impact
Epidemic Influenza
Transmission
Pandemic Influenza
Antigenic Variation
Antigenic Drift
Antigenic Shift
Emergence of Pandemic Viruses From Birds
Human Infections With H5 Viruses
Human Infections With H7 Viruses
Human Infections With H9 Viruses
Factors Controlling Host Range
Emergence of Pandemic Viruses From Swine
Clinical Findings
Uncomplicated Influenza
Complications of Influenza
Pulmonary Complications
Primary Influenza Viral Pneumonia
Secondary Bacterial Pneumonia
Pulmonary Complications in Immunosuppressed Patients
Other Pulmonary Complications
Nonpulmonary Complications
Myositis
Cardiac Complications
Toxic Shock Syndrome
Central Nervous Complications
Reye Syndrome
Pathogenesis
Cellular Pathogenesis
Virus Shedding
Cytokine Response
Histopathology
Pathophysiology
Host Response
Antibody Responses
Systemic Antibody Responses
Mucosal Antibody Responses
Cellular Responses
Diagnosis
Clinical Diagnosis
Laboratory Diagnosis
Polymerase Chain Reaction–Based Tests
Rapid Nucleic Acid Amplification Tests
Rapid Influenza Diagnostic Tests
Virus Isolation
Role of Viral Diagnosis in Clinical Decision Making
Prevention
Currently Available Vaccines
Egg-Grown Inactivated Influenza Vaccines (IIV-3, IIV-4)
Cell Culture–Derived Inactivated Vaccine (ccIIV-4)
Recombinant Hemagglutinin Expressed in Insect Cells (rIV-4)
High-Dose Egg-Grown Inactivated Vaccine (HD-IIV3)
MF-59 Adjuvanted Inactivated Influenza Vaccine (aIIV-3)
Intranasal Live-Attenuated Influenza Vaccine (LAIV-4)
Safety
Inactivated Vaccines
Live-Attenuated Vaccines
Immune Responses to Vaccination
Intramuscular Protein Vaccines
Intranasal Live-Attenuated Vaccine
Markers of Immune Responsiveness
Efficacy (Results of Randomized Prospective Studies)
Intramuscular Protein Vaccines
Intranasal Live Vaccines
Effectiveness (Results of Observational Studies)
Effects of Prior Vaccination
Comparisons of Live and Inactivated Vaccines
Secondary Protection
Maternal Immunization
Recommendations for Vaccine Use
Vaccines for Pandemic Influenza
Strategies for More Broadly Protective Vaccines
Antiviral Agents (Also See Chapter 45)
M2 Inhibitors: Amantadine and Rimantadine
Mechanism of Action and Activity
Pharmacology and Side Effects
Efficacy
Drug Resistance
Neuraminidase Inhibitors: Zanamivir, Oseltamivir, and Peramivir
Mechanism of Action and Activity
Pharmacology and Side Effects
Efficacy
Drug Resistance
Antiviral Agents in Development
Recommendations for Therapeutic Use of Antivirals
Chemoprophylaxis
Seasonal Prophylaxis
Family Prophylaxis
Outbreak Prophylaxis
Key References
References
i. Bunyaviridae
166 California Encephalitis, Hantavirus Pulmonary Syndrome, Hantavirus Hemorrhagic Fever With Renal Syndrome, and Bunyavirus Hemorrhagic Fevers
Short View Summary
Virology
Structure, Replication, and Antigenic Relationships
Epidemiology
Ecology and Distribution
California Encephalitis Viruses
Rift Valley Fever
Crimean-Congo Hemorrhagic Fever
Hantaviruses
Transmission to Humans
California Encephalitis Virus Group
Rift Valley Fever
Crimean-Congo Hemorrhagic Fever
Hantaviruses
Clinical Manifestations
California Encephalitis Virus Group
Rift Valley Fever
Crimean-Congo Hemorrhagic Fever
Hantaviruses
Hemorrhagic Fever With Renal Syndrome
Hantavirus Pulmonary Syndrome
Diagnosis
California Encephalitis
Riff Valley Fever and Congo-Crimea Hemorrhagic Fever Viruses
Hantaviruses
Therapy
Prevention
Other Bunyavirales of Concern
Jamestown Canyon Virus
Oropouche Virus
Toscana Virus
Ngari Virus
Severe Fever With Thrombocytopenia Syndrome Virus
Heartland Virus
Acknowledgment
Key References
References
j. Arenaviridae
167 Lymphocytic Choriomeningitis Virus, Lassa Virus, and the South American Hemorrhagic Fevers (Arenaviruses)
Short View Summary
Viral Characterization
Epidemiology
Lymphocytic Choriomeningitis
Lassa Fever
Other African Arenaviruses
South American Hemorrhagic Fevers
Other Arenaviruses
Pathogenesis
Rodents
Nonhuman Primates
Humans
Clinical Manifestations
Lymphocytic Choriomeningitis Virus
Lassa Fever
South American Hemorrhagic Fevers
Intrauterine Infection
Diagnosis
Treatment
Prevention
Key References
References
k. Retroviridae
168 Human T-Cell Leukemia Viruses (HTLV-1, HTLV-2)
Short View Summary
Structure and Molecular Organization
gag, pro, pol, and env
TAX
HBZ and APH
REX
Other Proteins Encoded by the pX Region
Biology
Laboratory Detection
Virus Isolation
Serologic Assays and Antigen Detection
Nucleic Acid Detection
Serologic Epidemiology
Geographic Distribution of Prevalence
Demographic Patterns in Prevalence
Incidence
Molecular Epidemiology
HTLV-1
HTLV-2
HTLV-3 and HTLV-4
Routes of Transmission
Mother-to-Child Transmission
Sexual Transmission
Parenteral Transmission
Immunology of HTLV Infection
Humoral Immune Responses
Cellular Immunity
Clinical Manifestations of HTLV Infections
HTLV-1–Associated Malignancies
HTLV-Associated Myelopathy
Other Diseases Associated With HTLV-1
Diseases Associated With HTLV-2
Therapy
Asymptomatic HTLV-1 and HTLV-2 Carriers
Adult T-Cell Leukemia
HTLV-1–Associated Myelopathy
Prevention
Conclusion
Acknowledgment
Key References
References
169 Human Immunodeficiency Viruses
Short View Summary
Overview of Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome
Origin and Classification of Human Retroviruses
Viral Transmission and Life Cycle
Biology of Transmission
Replication Cycle: Cell Entry and Integration
Replication Cycle: Virus Expression and Production of New Virions
The Virion
Genomic Organization
Virion Structural Proteins
Gag Proteins
Viral Enzymes
pol Gene Products
Protease
Reverse Transcriptase
Integrase
Envelope Glycoproteins and Viral Fusion
Virus-Cell Fusion
Viral Regulatory and Accessory Genes
Virus Regulation and the Long Terminal Repeat
Virus-Host Interactions
Viral Receptors, Chemokines, Receptors, and Tropism
Pathogenesis, T-Cell Depletion, and Viral Load
Viral Variation: Genetic and Phenotypic Variation
Malignancies and Human Immunodeficiency Virus
Conclusion
Acknowledgment
Key References
References
l. Picornaviridae
170 Introduction to the Human Enteroviruses and Parechoviruses
Enteroviruses
Virology
Physical Characteristics
Molecular Biology
Pathogenesis and Immunity in Enteroviral Infections
Pathogenesis
Viral Mutation During Natural Infection
Immunity and the Immune Response
Epidemiology of Enteroviral Infections
Age and Socioeconomic Status
Molecular Epidemiology
Transmission
Incidence of Infection and Illness
Incubation Period and Period of Communicability
Laboratory Diagnosis of Enteroviral Infections
Viral Isolation
Nucleic Acid Amplification Testing and Genomic Sequencing
Serology
Treatment and Prevention of Enteroviral Infections
Parechoviruses
Virology
Virus Types
Viral Diagnosis
Epidemiology
Key References
References
171 Poliovirus
Short View Summary
History
Pathophysiology
Virology
Pathogenesis
Clinical Manifestations
Incubation Period
Clinical Manifestations of Infection
Spinal Paralytic Poliomyelitis
Bulbar Paralytic Poliomyelitis
Polioencephalitis
Complications
Risk Factors
Differential Diagnosis
Laboratory Diagnosis
Prognosis
Therapy
Postpoliomyelitis Syndrome
Poliovirus Immunization
Poliovirus Vaccines
Inactivated Poliovirus Vaccine
Live-Attenuated Poliovirus Vaccine
Monovalent and Bivalent Oral Poliovirus Vaccines
Vaccine-Associated Paralytic Poliomyelitis
Use of Poliomyelitis Vaccines in the Developing World
Poliomyelitis in Developing Nations and Global Eradication
Vaccine-Derived Poliomyelitis Viruses
Key References
References
172 Coxsackieviruses, Echoviruses, and Numbered Enteroviruses (EV-A71, EVD-68, EVD-70)
Short View Summary
Central Nervous System Infections
Acute Viral Meningitis
Clinical Manifestations
Laboratory Diagnosis
Differential Diagnosis
Management and Prognosis
Encephalitis
Acute Flaccid Paralysis/Myelitis and Other Neurologic Complications
Exanthems
Rubelliform and Morbilliform Exanthems
Roseoliform Exanthems
Herpetiform Exanthems
Hand-Foot-and-Mouth Disease
Petechial Exanthems and Other Cutaneous Manifestations
Acute Respiratory Disease (EV-D68)
Herpangina
Clinical Manifestations
Differential Diagnosis
Myositis
Pleurodynia
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Management and Prognosis
Other Skeletal Myositis
Myopericarditis
Etiology and Pathogenesis
Clinical Manifestations
Diagnostic Virology
Management
Course and Prognosis
Dilated Cardiomyopathy
Coxsackievirus and Echovirus Disease in the Newborn
Epidemiology
Pathophysiology
Clinical Manifestations
Myocarditis
Hepatitis
Pneumonia
Diagnosis and Differential Diagnosis
Management
Chronic Meningoencephalitis in Agammaglobulinemic and Other Immunocompromised Patients
Clinical Manifestations
Prophylaxis and Therapy
Infections in Other Immunocompromised Patients
Acute Hemorrhagic Conjunctivitis
Epidemiology
Patterns of Transmission
Clinical Manifestations
Complications
Differential Diagnosis
Laboratory Diagnosis
Treatment and Prevention
Illnesses in Which the Etiologic Role of Enteroviruses Is Minor or Poorly Defined
Gastrointestinal Diseases
Other Diseases
Diabetes Mellitus
Enterovirus A71 Infections
Key References
References
173 Parechoviruses
Short View Summary
Historical Background
Virology
Epidemiology
Clinical Manifestations
Undifferentiated Febrile Illness/Sepsis Syndrome
Central Nervous System Infections
Meningitis
Encephalitis
Acute Flaccid Paralysis
Gastrointestinal Disease
Hemorrhage-Hepatitis Syndrome
Necrotizing Enterocolitis
Acute Gastroenteritis
Respiratory Disease
Miscellaneous Clinical Associations
Diagnosis
Therapy and Prevention
Key References
References
174 Hepatitis A Virus
Short View Summary
History
Classification and Physicochemical and Biologic Properties of Hepatitis a Virus
Structure
Resistance to Physical and Chemical Agents
Genome and Proteins
Antigenic Composition and Viral Diversity
Biology of Hepatitis A Virus in Cell Culture
Host Range
Epidemiology
Modes of Transmission
Person to Person
Foodborne and Waterborne
Bloodborne
Vertical
Worldwide Disease Patterns
Epidemiology in the United States
Potential Sources of Infection
Specific Groups and Settings of Infection
International Travel
International Adoption and Migrant and Refugee Populations
Users of Injection and Noninjection Drugs and People Experiencing Homelessness
Men Who Have Sex With Men
Transfusion and Health Care Settings
Foodborne and Waterborne Hepatitis A
Institutions Including Daycare for Children and Facilities for Persons With Developmental Disabilities
Pathogenesis
Incubation Period
Site of Viral Replication
Pathology
Manifestations
Signs and Symptoms
Complications
Therapy and General Management
Laboratory Diagnosis
Immunity
Prevention
Infection Prevention and Control
Passive Immunization
Active Immunization
Recommendations for Prevention
Postexposure Prophylaxis
Preexposure Prophylaxis
Disease-Control Strategies
Routine Vaccination of Children
Vaccination of Persons at Increased Risk of Hepatitis A Infection or Severe Consequences
Men Who Have Sex With Men
Users of Illicit Drugs
International Travelers
Close Contacts of Newly Arriving International Adoptees
Recipients of Blood or Plasma-Derived Products
Persons With Chronic Liver Disease
Other Groups and Settings
Hepatitis A Vaccination During Outbreaks
Directions for the Future
Acknowledgment
Key References
References
175 Rhinovirus
Short View Summary
Virology
Classification
Structure
Genomic Organization
Epidemiology
Age
Seasonality
Pathogenesis
Inflammatory Responses
Nasal Fluid Production
Transmission
Clinical Manifestations of Common Cold
Complications
Acute Bacterial Sinusitis
Acute Bacterial Otitis Media
Asthma
Exacerbation of Chronic Bronchitis
Lower Respiratory Tract Infections
Infections in Immunocompromised Patients
Diagnosis
Virus Isolation in Tissue Culture
Molecular Techniques
Antigen Detection
Neutralizing Antibody Assays
Therapy
Symptomatic Therapy
Antivirals
Interferon
Prevention
Virus Inactivation on Skin
Acid Inactivation of Virus
Intercellular Adhesion Molecule 1 Receptor Blockade
Vaccines
Acknowledgment
Key References
References
iii Caliciviridae and Other Gastrointestinal
176 Noroviruses and Sapoviruses (Caliciviruses)
Short View Summary
History
Virology
Taxonomy
Genome Organization
Antigenic Characterization
Epidemiology
Antigenic Variation
Seroprevalence
Transmission of Infection
Environmental Contamination
Pathogenesis
Immune Response
Clinical Manifestations
Diagnosis
Clinical Diagnosis
Laboratory Diagnosis
Therapy
Prevention
Vaccines
Key References
References
177 Astroviruses and Picobirnaviruses
Short View Summary
Astroviruses
Virology
Classification
Structure
Genomic Organization
Epidemiology
Pathogenesis
Clinical Manifestations
Immune Responses
Diagnosis
Therapy
Prevention
Picobirnaviruses
Key References
References
iv Unclassified Viruses
178 Hepatitis E Virus
Short View Summary
A Brief History
Genetics
Natural History of Hepatitis E
Burden of Disease
Geographic Distribution
Transmission
Clinical Presentation
Acute Hepatitis E
Chronic Hepatitis E
Extrahepatic Manifestations
Special Considerations
Pregnancy
Solid Organ Transplantation
Coinfections
Diagnostic Evaluation
General Principles
Serologic Evaluation
Molecular Diagnosis
Histopathology
Therapeutic Strategies
Acute Hepatitis E
Chronic Hepatitis E
Prevention
General Measures
Vaccination
Key References
References
B Prion Diseases
179 Prions and Prion Disease of the Central Nervous System (Transmissible Neurodegenerative Diseases)
Short View Summary
Brief History of Prion Disease Research
Molecular Biology and Pathophysiology of Prion Diseases
The Prion Protein
Infectious Prions
Propagation of Prions
In vitro Synthesis of Prions
Other Macromolecules Contributing to Prion Propagation
Species Barrier to Transmission of Prion Diseases
Prion Strains
Transmission by Oral Exposure
Neurodegeneration in Prion Disease
Yeast Prions
Prion-Like Behavior of Other Neurodegenerative Diseases
Human Prion Diseases
Classification and Epidemiology of Human Prion Disease
Epidemiology of Creutzfeldt-Jakob Disease
Sporadic Creutzfeldt-Jakob Disease
Epidemiology
Clinical Features
Strains
Familial Prion Disease
Overview and Epidemiology
Gerstmann-Sträussler-Scheinker Syndrome
Fatal Familial Insomnia
Long-Duration Genetic Prion Disease
Polymorphisms in PRNP
Infectiously Acquired Human Prion Disease
Kuru
Variant Creutzfeldt-Jakob Disease
Epidemiology
Clinical Features
Transmission by Blood Products
Neuropathology
vCJD Caused by Exposure to BSE
Genetics of vCJD Susceptibility
Subclinical vCJD
Iatrogenic Creutzfeldt-Jakob Disease
Transmission Through Dura Mater Grafts
Transmission Through Cadaver-Derived Hormones
Transmission Through Corneal Transplants
Transmission Through Surgical Instruments
Inadvertent Surgical Exposure
Blood Products and Sporadic CJD
CJD in Health Professionals
Nosocomial and Iatrogenic Infection Risk
Prion Disease in Ruminants
Atypical Forms of Bovine Spongiform Encephalopathy
Atypical Forms of Scrapie
Chronic Wasting Disease
Camel Prion Disease
Laboratory Diagnosis of Prion Disease
Prion Disease Mimics
Specific Testing for Prion Disease (RT-QuIC)
Supportive Testing for Prion Disease
CSF Proteins
Brain Imaging
Electroencephalography in Creutzfeldt-Jakob Disease
Histology of Creutzfeldt-Jakob Disease
Tissue Biochemical Tests
Genetic Testing and Creutzfeldt-Jakob Disease
Prion Disease Therapy
Key References
References
C Chlamydial Diseases
180 Chlamydia trachomatis (Trachoma and Urogenital Infections)
Short View Summary
Chlamydial Biology
Antigenic and Genetic Diversity
Pathogenesis
Immunity
Laboratory Diagnosis
Nucleic Acid Amplification Tests
Antigen Detection and Nucleic Acid Hybridization
Isolation in Cell Culture
Cytologic Diagnosis
Rapid Tests
Serology
Clinical Manifestations
Trachoma
Treatment
Oculogenital Disease in Adults
Inclusion Conjunctivitis
Urogenital Infections
Urogenital Infections in Men
Urethritis
Epididymitis and Prostatitis
Sexually Reactive Arthritis
Urogenital Infections in Women
Cervicitis and Urethritis
Pelvic Inflammatory Disease
Infertility and Ectopic Pregnancy
Pregnancy Complications
Extragenital Infections
Proctitis (Rectal Infections)
Oropharyngeal Infections
Other Infections
Treatment of Genital and Ocular Infections in Adults
Perinatal Infections
Neonatal Inclusion Conjunctivitis
Infant Pneumonia
Diagnosis of Neonatal Inclusion Conjunctivitis and Infant Pneumonia
Prevention and Treatment of Infant Infections
Chlamydial Infections in Prepubertal Children
Lymphogranuloma Venereum
Classic LGV
LGV Proctitis and Proctocolitis
Diagnosis of Lymphogranuloma Venereum
Treatment of Lymphogranuloma Venereum
Prevention Strategies
Key References
References
181 Psittacosis (Due to Chlamydia psittaci)
Short View Summary
Epidemiology
Clinical Manifestations and Differential Diagnostic Considerations
Laboratory Findings
Pathologic Findings
Diagnosis
Therapy
Prevention
Key References
References
182 Chlamydia pneumoniae
Short View Summary
History
Microbiology
Laboratory Testing for Chlamydia pneumoniae
Cell Culture
Antigen Detection
Single and Multiplex Nucleic Acid Amplification Tests
Serologic Testing
Epidemiology
Clinical Manifestations
Therapy
Chlamydia pneumoniae and Chronic Disease in Humans
Chlamydia pneumoniae and Asthma
Therapy
Chlamydia pneumoniae and Other Chronic Diseases
Chlamydia pneumoniae and Atherosclerosis
Chlamydia pneumoniae and Multiple Sclerosis
Key References
References
D Mycoplasma Diseases
183 Mycoplasma pneumoniae and Atypical Pneumonia
Short View Summary
History
Microbiology
Epidemiology
Immunology and Resistance
Innate Immunity
Adaptive Immunity
Cold Agglutinins
Resistance and Susceptibility to Infection
Pathology
Disease Syndromes
Respiratory Illnesses
Other Illnesses
Dermatologic Syndromes
Raynaud Phenomenon
Cardiac Syndromes
Neurologic Syndromes
Musculoskeletal, Renal, and Hematologic Syndromes
Diagnosis
Cold Agglutinins
Culture
Detection of Mycoplasma pneumoniae–Specific Antibodies
Detection of Mycoplasma pneumoniae–Specific Antigens
Detection of Mycoplasma pneumoniae–Specific Nucleic Acids
Treatment
Prevention
Infection Control
Vaccination
Key References
References
184 Genital Mycoplasmas: Mycoplasma genitalium, Mycoplasma hominis, and Ureaplasma Species
Short View Summary
Taxonomy and Microbiology
Epidemiology
Clinical Manifestations
Ureaplasmas
Mycoplasma hominis
Mycoplasma genitalium
Laboratory Diagnosis
Therapy
Key References
References
E Rickettsioses, Ehrlichioses, and Anaplasmoses
185 Introduction to Rickettsioses, Ehrlichioses, and Anaplasmoses
Bacteriology
History and Emerging Diseases
Pathophysiology
Genetics
Epidemiology
Clinical Findings
Diagnosis
Treatment
Remaining Questions and Perspectives
References
186 Rickettsia rickettsii and Other Spotted Fever Group Rickettsiae (Rocky Mountain Spotted Fever and Other Spotted Fevers)
Short View Summary
Rocky Mountain Spotted Fever
The Pathogen
Virulence Factors
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Treatment
Prevention
Other Spotted Fever Group Rickettsioses
Boutonneuse Fever (Mediterranean Spotted Fever)
Spotted Fevers: Moderate Severity
Spotted Fevers: Mild Severity
Flea-borne Spotted Fever
Diagnosis
Treatment
Key References
References
187 Rickettsia akari (Rickettsialpox)
Short View Summary
Etiology
Epidemiology
Clinical Manifestations
Diagnosis
Therapy
References
188 Coxiella burnetii (Q Fever)
Short View Summary
Pathogen
Epidemiology
History
Zoonotic Sources
Transmission Between Humans
Incidence
Outbreaks
Pathogenesis
Clinical Manifestations
Self-Limited Febrile Illness
Pneumonia
Radiologic Findings
Outcome
Laboratory Findings
Diagnosis of Acute Q Fever
Treatment of Acute Q Fever
Monitoring Patients With Acute Q Fever
Endocarditis
Clinical Manifestations of Endocarditis
Diagnosis of Endocarditis
Treatment of Q Fever Endocarditis
Follow-Up
Hepatitis
Neurologic Manifestations
Q Fever in the Immunocompromised Host
Other Manifestations of Q Fever
Q Fever in Pregnancy
Post–Q Fever Fatigue Syndrome
Prevention
Vaccination
Risk Reduction
Key References
References
189 Rickettsia prowazekii (Epidemic or Louse-Borne Typhus)
Short View Summary
Microbiology
Epidemiology
Louse-Borne Epidemic Typhus
Sylvatic Typhus
Pathogenesis
Clinical Manifestations
Louse-Borne Epidemic Typhus
Sylvatic Typhus
Recrudescent Typhus
Diagnosis
Treatment
Prevention
Key References
References
190 Rickettsia typhi (Murine Typhus)
Short View Summary
Microbiology
Epidemiology
Pathology and Pathogenesis
Clinical Manifestations
Signs and Symptoms
Laboratory Features
Diagnosis
Treatment and Prevention
Key References
References
191 Orientia tsutsugamushi (Scrub Typhus)
Short View Summary
History
Definition
Ecology and Epidemiology
Microbiology
Diagnosis
Immune Response
Therapy
Prevention
Key References
References
192 Ehrlichia chaffeensis (Human Monocytotropic Ehrlichiosis), Anaplasma phagocytophilum (Human Granulocytotropic Anaplasmosis), and Other Anaplasmataceae
Short View Summary
Etiology
Epidemiology and Epizootiology of Human Monocytotropic Ehrlichiosis
Epidemiology and Epizootiology of Human Granulocytic Anaplasmosis
Pathogenesis and Pathology
Human Monocytotropic Ehrlichiosis
Human Granulocytotropic Anaplasmosis
Clinical Manifestations
Human Monocytotropic Ehrlichiosis
Signs and Symptoms
Course
Diagnosis
Differential Diagnosis
Ehrlichiosis Caused by Ehrlichia ewingii and Ehrlichia muris
Human Granulocytotropic Anaplasmosis
Signs, Symptoms, and Course
Diagnosis
Treatment and Prevention
Candidatus Neoehrlichia Mikurensis Human Infections
Prevention of Ehrlichiosis and Anaplasmosis
Sennetsu Neorickettsiosis
Key References
References
F Bacterial Diseases
193 Introduction to Bacteria and Bacterial Diseases
Classification of Bacteria
Variation in Bacterial Infections
Polymorphism and Bacterial Infection
Bacteria as “New” Causes for “Old” Diseases
Bacterial Evolution
Bacteria as Therapeutics
Key References
References
i. Gram-Positive Cocci
194 Staphylococcus aureus (Including Staphylococcal Toxic Shock Syndrome)
Short View Summary
The Microorganism
Habitat
Culture and Identification
Morphologic Variants
Molecular Diagnosis
Molecular Typing
Pulsed-Field Gel Electrophoresis
Multilocus Sequence Typing
Spa Typing and Double-Locus Spa-ClfB Typing
Pathogenesis
Regulation and Virulence Determinants
Regulation
agr and Other Two-Component Regulatory Systems
DNA-Binding Proteins
Small RNAs and Endoribonuclease III
Role in Pathogenesis
Ecologic and Epidemiologic Implication of agr
The Journey to Invasive Disease
Mucosal and Skin Colonization
Host Invasion
Contribution of Coagulation
Immune Evasion
Escaping Phagocytosis
Luring Complement
Resisting Oxidative Burst
Resisting Antimicrobial Peptides
Killing Leukocytes
Panton-valentine leukocidin.
Escaping Cell-Mediated Immunity
Producing Biofilm
Exfoliative Toxins and Staphylococcal Scalded Skin Syndrome
Molecular Pathogenesis of Staphylococcal Scalded Skin Syndrome
Clinical Aspects
Superantigens
Toxic Shock Syndrome
Menstrual Toxic Shock Syndrome
Nonmenstrual Toxic Shock Syndrome
Predisposing Factors
Diagnosis
Therapy and Prevention
Enterotoxins and Food Poisoning
Other Implications of Superantigens
Genomics and Mobile Genetic Elements
Comparative Genomics and Evolution
Staphylococcus aureus Cross-Species Jump Between Humans and Animals
Pathogenicity and Genomic Islands
Resistance Island Staphylococcal Cassette Chromosome mec
Antibiotic Resistance
β-Lactams
Resistance to Penicillin
Methicillin-Resistant Staphylococcus aureus
Health Care–Associated Versus Community-Acquired Methicillin-Resistant Staphylococcus aureus
Mechanism of Methicillin Resistance
Glycopeptides
Therapeutic Monitoring of Vancomycin in Adult Patients
Intermediate Resistance to Glycopeptides
Full Resistance to Glycopeptides
Daptomycin
Protein Synthesis Inhibitors
MLSB Antibiotics
Drug Efflux
Oxazolidinones
Quinolones
Mechanisms of Resistance
Alternative Treatments
Alternatives Against Non–Life- Threatening Infections
Tigecycline
Aminomethylcyclines
Quinupristin-Dalfopristin
Lipoglycopeptides
Alternatives Against Severe Infections
Combination Therapy
β-Lactams With Improved Penicillin-Binding Protein 2A Affinity
Development of Nonantibiotic and Vaccine Strategies
Antimicrobial Peptides
Virulence Modulation
Immunomodulation
Antibiotic Resensitization
Phage Lysins
Phage Therapy
Vaccines
Clinical Aspects and Epidemiology
Clinical Spectrum
Risk Factors for Staphylococcus aureus Infection
The Burden of Antibiotic Resistance
Carriage of Staphylococcus aureus
Carriage of Methicillin-Resistant Staphylococcus aureus
Preventive Measures to Limit Health Care–Associated Infections Methicillin-Resistant Staphylococcus aureus Infections
Clinical Syndromes
Skin and Soft Tissues Infections
Classification
Impetigo
Folliculitis
Furuncles and Carbuncles
Hidradenitis Suppurativa
Mastitis
Surgical Site Infection
Erysipelas, Cellulitis, and Fasciitis
Management of Skin and Soft Tissue Infection
Bloodstream Infection
Community-Onset Bacteremia
Nosocomial and Health Care–Associated Bloodstream Infection
Management of Staphylococcus aureus Bloodstream Infection
Infective Endocarditis
Epidemiology
Pathogenesis
Role of Bacterial Adhesins
Role of Platelets
Host Defenses and Prevention
Clinical Spectrum
Vascular Complications
Neurologic Complications
Diagnosis
Management of Staphylococcus aureus Endocarditis
Management of Right-Sided Endocarditis in Injection Drug Users
Infections of the Central Nervous System
Meningitis
Spinal Epidural Abscess
Pulmonary Infections
Epidemiology
Clinical Spectrum
Therapy
Osteoarticular Infections
Osteomyelitis
Epidemiology
Pathogenesis
Clinical Features
Diagnosis
Therapy
Native Joint Septic Arthritis
Septic Bursitis
Prosthetic Joint Infections
Pyomyositis
Acknowledgment
Key References
References
195 Staphylococcus epidermidis and Other Coagulase-Negative Staphylococci
Short View Summary
Microbiology and Ecology
Antibiotic Resistance
Molecular Epidemiology
Pathogenesis
Virulence Factors
Biofilm
Adherence
Maturation
Dispersal
Other Virulence Factors
Phenol Soluble Modulins
Poly-Gamma-dl-Glutamic Acid
Antimicrobial Peptide Resistance
Lantibiotics
Other Coagulase-Negative Species
Epidemiology and Clinical Syndromes
Colonization and Transmission
Bacteremia
Intravascular Catheter Infections
Endocarditis
Cardiovascular Implantable Electronic Devices
Vascular Grafts
Orthopedic Prosthetic Device Infections
Cerebrospinal Fluid Shunt Infections
Surgical Site Infections
Peritoneal Dialysis Catheter–Associated Infections and Peritoneal Dialysis–Associated Peritonitis
Endophthalmitis
Urinary Tract Infection
Infections of Genitourinary Prostheses
Mastitis and Infections of Breast Implants
Miscellaneous Prosthetic Device Infections, Implant Infections, and Other Infections
Patient Populations at Increased Risk of Infection With Coagulase-Negative Staphylococci
Transplant Patients and Neutropenic Hosts
Neonates
Burn Patients
Non–Staphylococcus epidermidis Species of Coagulase-Negative Staphylococci
Staphylococcus haemolyticus
Staphylococcus lugdunensis
Staphylococcus saprophyticus
Other Species of Coagulase-Negative Staphylococci
Novel Therapeutic Options for Infections Due to Coagulase-Negative Staphylococci
Key References
References
196 Classification of Streptococci
References
197 Streptococcus pyogenes
Short View Summary
History
Description of the Pathogen
Somatic Constituents
Extracellular Products
Streptococcal Pharyngitis
Epidemiology
Clinical Manifestations
Scarlet Fever
Suppurative Complications
Nonsuppurative Complications
Diagnosis
Throat Culture
Rapid Antigen Detection Tests
Therapy
Streptococcal Pyoderma
Epidemiology
Bacteriology and Immunology
Clinical Manifestations
Therapy and Prevention
Complications
Invasive Streptococcal Infections of Skin and Soft Tissues
Erysipelas
Streptococcal Cellulitis
Necrotizing Fasciitis (Streptococcal Gangrene)
Diagnosis and Differential Diagnosis
Myositis and Myonecrosis
Streptococcal Toxic Shock Syndrome
Pathogenesis
Mechanisms of Shock and Organ Failure
Clinical Manifestations
Management
Source Control
Fluid Resuscitation
Antimicrobial Therapy
Management in the Intensive Care Unit
Dialysis and Hemoperfusion
Intravenous Immune Globulin
Bacteremia
Other Streptococcal Infections
Prophylaxis and Risk for Secondary Cases of Streptococcal Toxic Shock Syndrome
Key References
References
198 Nonsuppurative Poststreptococcal Sequelae
Short View Summary
Rheumatic Fever
History
Etiology and Pathogenesis
Pathologic Findings
Epidemiology
Clinical Manifestations
Diagnosis
Therapy and Prognosis
Prevention
Glomerulonephritis
History
Etiology and Pathogenesis
Pathologic Characteristics
Epidemiology
Clinical and Laboratory Features
Diagnosis
Therapy
Prevention
Prognosis
Key References
References
Additional Reading
199 Streptococcus pneumoniae
Short View Summary
History
Microbiology
Epidemiology
Pathogenetic Mechanisms
Colonization
Pneumococcal Capsular Serotypes and Progression From Colonization to Disease
Immunologic Mechanisms of Defense Against and Susceptibility to S. pneumoniae Infection
Factors That Predispose to Pneumococcal Infection
HIV Infection
Clinical Syndromes
Otitis Media
Sinusitis
Meningitis
Acute Exacerbation of Chronic Bronchitis
Pneumonia
Overview
Pathogenesis
Predisposing Factors
Symptoms and Physical Findings
Radiographic Findings
General Laboratory Findings
Diagnostic Microbiology
Complications
Other Infectious Syndromes
Noninfectious Syndromes
Antibiotic Susceptibility and Resistance
Definitions of Antibiotic Susceptibility
Mechanisms of Antibiotic Susceptibility and Resistance
Prevalence of Resistance
Therapy
Otitis Media
Sinusitis
Pneumonia
Outpatient Therapy
Inpatient Therapy
Meningitis
Endocarditis
Prevention of Pneumococcal Infections
Antibody Responses to Pneumococcal Capsular Polysaccharides
Pneumococcal Conjugate Vaccine Efficacy in Children
Efficacy of 23-Valent Pneumococcal Polysaccharide and 13-Valent Polysaccharide Conjugate Vaccine in Adults
Impact of Infant Immunization on Adult Disease
Vaccine Protection During HIV Infection
Vaccine Recommendations
Key References
References
200 Enterococcus Species, Streptococcus gallolyticus Group, and Leuconostoc Species
Short View Summary
Historical Background
Microbiology and Taxonomy
Colonization, Virulence, and Genomics
Epidemiology of Enterococcal Infections
Clinical Manifestations of Enterococcal Disease
Bacteremia and Endocarditis
Urinary Tract Infections
Meningitis
Intraabdominal and Pelvic Infections
Neonatal Infections
Skin, Soft Tissue, and Other Infections
Therapy and Antimicrobial Resistance
Combination of β-Lactam and Aminoglycosides or Cephalosporins
Glycopeptides and Lipoglycopeptides
Daptomycin
Linezolid
Tigecycline
Quinupristin-Dalfopristin
Other Antienterococcal Antimicrobials
Streptococcus Gallolyticus (Bovis) Group
Leuconostoc Species
Key References
References
201 Streptococcus agalactiae (Group B Streptococci)
Short View Summary
Historical Perspective
Description
Classification and Morphologic Characteristics
Identification
Serologic Typing
Epidemiology and Transmission
Asymptomatic Colonization
Transmission
Incidence and Serotype Distribution of Isolates
Pathogenetic Mechanisms
Adherence
Invasion
Bacterial Virulence Factors
Host Factors
Clinical Manifestations
Primary Bacteremia
Infections of the Female Genital Tract
Infections in Infants
Pneumonia
Endocarditis
Arthritis
Osteomyelitis
Skin and Soft Tissue Infections
Meningitis
Urinary Tract Infections
Uncommon Manifestations of Infection
Recurrent Invasive Group B Streptococcal Infection
Diagnosis
Treatment
Prevention
Group B Streptococcal Vaccines
Key References
References
202 Viridans Streptococci, Nutritionally Variant Streptococci, and Groups C and G Streptococci
Short View Summary
Overview
Microbiology
Viridans Streptococci
Streptococcus anginosus Group
Nutritionally Variant Streptococci: Abiotrophia sp. and Granulicatella spp.
Epidemiology
Viridans Streptococci and the Streptococcus anginosus Group
Nutritionally Variant Streptococci: Abiotrophia sp. and Granulicatella spp.
Virulence
Viridans Streptococci
Streptococcus anginosus Group
Nutritionally Variant Streptococci: Abiotrophia sp. and Granulicatella spp.
Clinical Manifestations
Abscesses: Streptococcus anginosus Group
Aseptic Meningitis: Viridans Streptococci
Subacute Bacterial Endocarditis: Viridans streptococci, Streptococcus anginosus, and Nutritionally Variant Streptococci
Positive Blood Cultures and Nonsterile Body Sites: Viridans Streptococci
Therapy: Viridans Streptococci
Subacute Bacterial Endocarditis
Meningitis: Viridans Streptococci
Endophthalmitis: Viridans Streptococci
Reactive and Septic Arthritis: Viridans Streptococci, Group C Streptococcus, and Group G Streptococcus
Abscesses: Streptococcus anginosus Group
Resistance: Viridans Streptococci and Nutritionally Variant Streptococci—Abiotrophia sp. and Granulicatella spp.
Groups C and G Streptococci
Group C Streptococci
Habitat
Microbiology
Virulence
Clinical Manifestations
Treatment
Group G Streptococci
Habitat
Microbiology
Virulence
Clinical Manifestations
Treatment
Streptococcus suis
Viridans-Like Organisms
Rothia
Pediococcus
Key References
References
203 Streptococcus anginosus Group
Short View Summary
Epidemiology
Microbiology
Molecular Subspecies
Phenotypic Characteristics
Taxonomy
Molecular Diagnostic Methods
Pathogenesis
Mixed Infections Contribute to Abscess Formation
Virulence Factors
Cytotoxins
Hydrolytic Enzymes
Immune Factors
Superantigens
Resistance to Phagocytosis
Clinical Presentations
Head and Neck Infections
Intracranial Complications of Head and Neck Infections
Bacteremia
Endocarditis
Central Nervous System Infections
Intraabdominal Infections
Thoracic Infections
Pulmonary Complications
Therapy
Key References
References
ii. Gram-Positive Bacilli
204 Corynebacterium diphtheriae (Diphtheria)
Short View Summary
History
The Pathogen
Epidemiology
Pathogenesis
Clinical Manifestations
Respiratory Tract Diphtheria
Anterior Nasal
Faucial
Laryngeal and Tracheobronchial
Cardiac Toxicity
Neurologic Toxicity
Other Complications
Cutaneous Diphtheria
Invasive Disease
Other Sites
Diagnosis
Therapy
Prevention
Key References
References
205 Other Coryneform Bacteria, Arcanobacterium haemolyticum, and Rhodococci
Short View Summary
Coryneform Bacteria Other Than Corynebacterium diphtheriae
Taxonomy
Microbiology
Nonlipophilic, Fermentative Corynebacteria
Corynebacterium ulcerans and Corynebacterium pseudotuberculosis
Corynebacterium xerosis
Corynebacterium striatum
Corynebacterium minutissimum
Corynebacterium amycolatum
Corynebacterium glucuronolyticum
Other Nonlipophilic, Fermentative Corynebacteria
Nonlipophilic, Nonfermentative Corynebacteria
Corynebacterium afermentans subsp. afermentans
Corynebacterium auris
Corynebacterium pseudodiphtheriticum
Corynebacterium propinquum
Lipophilic Corynebacteria
Corynebacterium jeikeium
Microbiology
Pathogenicity
Treatment
Corynebacterium urealyticum
Microbiology
Pathogenicity
Treatment
Other Lipophilic Corynebacteria
Arcanobacteria
Arcanobacterium haemolyticum
Microbiology
Infections in Humans
Treatment
Trueperella (Arcanobacterium) pyogenes
Trueperella (Arcanobacterium) bernardiae
Miscellaneous Coryneform Bacteria
Turicella otitidis
Arthrobacter Species
Brevibacterium Species
Dermabacter hominis
Rothia dentocariosa and Rothia mucilaginosa
Oerskovia and Cellulosimicrobium Species
Microbacterium Species
Leifsonia aquatica
Other medically relevant coryneform bacteria
Rhodococci
Taxonomy
Rhodococcus equi
Epidemiology
Microbiology
Pathogenicity
Clinical Manifestations
Treatment
Other Rhodococcus Species and Related Genera
Key References
References
206 Listeria monocytogenes
Short View Summary
Definition
Epidemiology
Microbiology
Pathogenesis
Clinical Manifestations
Acute Febrile Gastroenteritis
Cutaneous Listeriosis
Invasive Listeriosis
Pregnancy
Neonatal Infection
Bacteremia
Neurolisteriosis
Focal Invasive Infection
Diagnosis
Treatment
Prevention
Key References
References
207 Bacillus anthracis (Anthrax)
Short View Summary
Epidemiology
Microbiology
Clinical Manifestations and Diagnosis
Cutaneous Anthrax
Differential Diagnosis of Cutaneous Anthrax
Laboratory Diagnosis of Cutaneous Anthrax
Injectional Anthrax
Inhalational or Pulmonary Anthrax
Diagnosis of Inhalational Anthrax
Gastrointestinal Anthrax
Anthrax Meningitis
Therapy
Cutaneous Anthrax Without Systemic Manifestations
Cutaneous Anthrax (With Systemic Manifestations), Injectional Anthrax, Inhalational Anthrax, Gastrointestinal Anthrax, and Meningeal Anthrax
Management of Pleural Effusion and Ascites
Role of Corticosteroids and Management of Severe Edema
Anthrax Antitoxin Therapies (Immunotherapeutics)
Prevention
Anthrax as an Agent of Bioterrorism
History of Bacillus anthracis as a Bioterrorist Agent
Dissemination of Anthrax as a Bioterrorist Agent
Outbreak Characteristics After Use of Anthrax as a Bioterrorist Agent
Anthrax Countermeasures
Diagnostics
Antibiotics
Vaccines
Antitoxin Immunotherapy
Infection Control
Remediation (Decontamination)
Key References
References
208 Bacillus Species and Related Genera Other Than Bacillus anthracis
Short View Summary
Microbiology
Epidemiology
Pseudoinfection and Contamination
Commercial Uses of Bacillus Species
Adherence Properties
Clinical Manifestations
Food Poisoning
Systemic Infections
Central Nervous System Infections
Respiratory Infections
Eye Infections
Soft Tissue, Skin, and Muscle Infection
Prevention
Therapy
Key References
References
209 Erysipelothrix rhusiopathiae
Short View Summary
Microbiology
Epidemiology
Pathogenesis
Clinical Manifestations
Diagnosis
Therapy and Prevention
Key References
References
210 Whipple Disease
Short View Summary
Etiology
Epidemiology and Pathogenesis
Pathology
Clinical Features and Diagnosis
Therapy and Prognosis
Key References
References
iii. Gram-Negative Cocci
211 Neisseria meningitidis
Short View Summary
Definition and History
Microbiology
Biology and Pathogenesis
Meningococcal Colonization and Transmission
Host Susceptibility
Epidemiology
Clinical Manifestations and Pathophysiology
Meningococcemia
Meningitis
Rash of Meningococcal Disease
Complement Deficiency and Meningococcal Disease (See also Chapter 9)
Chronic Meningococcemia
Primary (Purulent) Pericarditis
Septic Arthritis
Respiratory Tract Infections
Conjunctivitis
Meningococcal Urethritis and Proctitis
Complications
Family and Community Impact
Diagnosis
Treatment
Antibiotic Therapy
Adjunctive Therapy and Supportive Care
Prevention
Chemoprophylaxis
Immunoprophylaxis
Immune Correlates of Protection and Meningococcal Polysaccharide Vaccines
Meningococcal Conjugate Vaccines
Serogroup B Vaccines
Duration of Protection
Immunologic Memory and Interference
Vaccine Population Coverage and Effectiveness
Herd Protection and Vaccine Strategies
Meningococcal Vaccine Recommendations
Adolescents and Adults
Infants and Young Children
Outbreak Immunoprophylaxis
Hajj and Umrah Pilgrimages
Eculizumab (Solaris)
Future Meningococcal Disease Vaccine Prevention Strategies
Key References
References
212 Neisseria gonorrhoeae (Gonorrhea)
Short View Summary
The Organism
Description
Growth and Cultivation
Surface Structures
Type IV Pili
Outer Membrane
Strain Typing
Genetics
Plasmids
Chromosomal Mutations and Transformation
Pathobiology of Gonococcal Infection
Infection of the Male Urethra
Infection of the Lower Female Genital Tract
Infection of the Upper Female Genital Tract
The Human Immune Response to Neisseria gonorrhoeae
Adaptive Immune Response
Innate Immune Response
Epidemiology
Incidence
Transmission
Antimicrobial Resistance
Clinical Manifestations
Genital Infection in Men
Uncomplicated Infection
Localized Complications
Uncomplicated Urogenital Infection in Women
Rectal Gonococcal Infection
Pharyngeal Infection
Other Local Manifestations
Pelvic Inflammatory Disease
Perihepatitis
Gonorrhea in Pregnancy
Disseminated Gonococcal Infection
Neonatal and Pediatric Infections
Diagnosis
Culture
Nucleic Acid Amplification Tests
Gram-Stained Smears
Other Diagnostic Methods
Therapy
Uncomplicated Gonorrhea in Adults
Initial Single-Dose Treatment
Follow-Up of Patients Treated for Uncomplicated Gonorrhea
Pelvic Inflammatory Disease
Acute Epididymitis
Disseminated Gonococcal Infection
Gonorrhea in Children
Management of Sex Partners
Prevention and Control
Public Health Strategies
Condoms and Microbicides
Other Prevention Strategies
Key References
References
213 Moraxella catarrhalis, Kingella, and Other Gram-Negative Cocci
Short View Summary
Moraxella Catarrhalis
History
Microbiology
Epidemiology and Respiratory Tract Colonization
Pathogenesis
Clinical Manifestations
Otitis Media
Lower Respiratory Tract Infections in Chronic Obstructive Pulmonary Disease
Pneumonia in Older Adults
Nosocomial Respiratory Tract Infections
Sinusitis
Bacteremia
Therapy
Other Neisseria
Other Moraxella
Kingella
History and Microbiology
Epidemiology and Respiratory Tract Colonization
Clinical Manifestations
Skeletal Infections
Endocarditis
Bacteremia
Other Infections
Therapy
Key References
References
iv Gram-Negative Bacilli
214 Vibrio cholerae
Short View Summary
Classification and Genomics
Pathogenicity
Epidemiology
Clinical Manifestations
Diagnosis
Treatment
Immune Responses
Prevention and Vaccines
Key References
References
215 Other Pathogenic Vibrios
Short View Summary
Vibrio parahaemolyticus
Epidemiology
Clinical Manifestations
Laboratory Findings
Differential Diagnosis
Therapy
Prevention
Vibrio vulnificus
Clinical Manifestations
Differential Diagnosis
Therapy
Prevention
Vibrio alginolyticus
Halophilic Vibrios
Nonhalophilic Vibrios: Non-O1/O139 Vibrio cholerae and Vibrio mimicus
Epidemiology
Clinical Manifestations
Laboratory Findings
Therapy
Prevention
Key References
References
216 Campylobacter jejuni and Related Species
Short View Summary
Microbiology
Epidemiology
Pathogenesis and Pathologic Characteristics
Immunology
Clinical Manifestations
Campylobacter jejuni Infections
Campylobacter fetus Infections
Infection Caused by Other Enteric Campylobacter Species
Diagnosis
Bacteriologic Studies
Molecular Techniques and Immunoassays
Direct Examination of Feces
Therapy
Antibiotic Resistance
Resistance to Fluoroquinolones
Resistance to Macrolides
Prognosis
Prevention
Key References
References
217 Helicobacter pylori and Other Gastric Helicobacter Species
Short View Summary
Microbiology
Epidemiology
Pathology and Pathogenesis
Clinical Consequences Associated With H. pylori Colonization
Gastrointestinal Diseases
Acute Acquisition
Persistent Colonization
Duodenal Ulceration
Gastric Ulceration
Gastric Carcinoma
Gastric Lymphoma
Esophageal Diseases
Asthma and Related Disorders
Metabolic Disorders
Idiopathic Thrombocytopenic Purpura
Other Inverse Associations
Overview of Clinical Consequences
Diagnosis
Therapy
Indications for Treatment
Treatment Regimens
Benefits and Risks of Antibiotic Therapy
Prevention of H. pylori Acquisition
Other Gastric Helicobacters
Key References
References
218 Enterobacteriaceae
Short View Summary
General Properties
Epidemiology
Structural and Surface Antigenic Features
Inner Membrane
Periplasmic Space
Peptidoglycan Cell Wall
Outer Membrane
Other Surface Polysaccharides and Capsules
Flagella
Pili
Virulence Factors
Adhesins
Toxins and Secretion Systems
Lipopolysaccharide and Capsules
Iron Acquisition
Specific Organisms
Escherichia
General Clinical Principles Related to Diarrheagenic Escherichia coli
Enterotoxigenic Escherichia coli
Enteropathogenic Escherichia coli
Shiga Toxin–Producing Escherichia coli Including Enterohemorrhagic Escherichia coli
Enteroaggregative Escherichia coli
Enteroinvasive Escherichia coli
Diffusely Adherent Escherichia coli
Adherent-invasive Escherichia coli
Extraintestinal Pathogenic Escherichia coli
Uropathogenic Escherichia coli
Neonatal Meningitis–Associated Escherichia coli
Sepsis-Associated Escherichia coli
Klebsiella
Enterobacter Species, Pantoea agglomerans, and Chronobacter sakazakii
Serratia Species
Citrobacter Species
Hafnia alvei
Proteus, Providencia, and Morganella
Other Genera
Acknowledgment
Key References
References
219 Pseudomonas aeruginosa and Other Pseudomonas Species
Short View Summary
Microbiology
The Pseudomonas aeruginosa Genome
Pseudomonas aeruginosa and the Human Microbiota
Virulence Factors
Pili
Type I and II Secretion Systems
Type III Secretion Systems
Quorum-Sensing Molecules
Other Virulence Factors
Epidemiology
Transmission Dynamics of Pseudomonas aeruginosa and Reservoirs
Antimicrobial Resistance
Resistance Mechanisms
Intrinsic Resistance
Decreased Permeability of the Outer Membrane
Efflux Pumps
Antimicrobial-Modifying Enzymes
Acquired Resistance
Aminoglycoside-Modifying Enzyme
Treatment of Pseudomonas aeruginosa Infections
Infections Caused by Pseudomonas aeruginosa
Bloodstream Infections
Infective Endocarditis
Pneumonia
Pneumonia Associated With Hospital Exposure
Hospital-Acquired (Nosocomial) Pneumonia
Hospital-Acquired Pneumonia Among Ventilated Patients
Hospital-Acquired Pneumonia Among Nonventilated Patients
Health Care–Associated Pneumonia
Community-Acquired Pneumonia
Cystic Fibrosis
Bone and Joint Infections
Sternoclavicular Septic Arthritis
Septic Arthritis of the Symphysis Pubis
Vertebral Osteomyelitis
Skull Base Osteomyelitis
Osteomyelitis Related to Nail Puncture Wounds
Combat-Related Osteomyelitis
Antimicrobial Therapy for Arthritis and Osteomyelitis
Skin and Soft Tissue Infections
Paronychia and Green Nail Syndrome
Interdigital Infections
Hot Tub Folliculitis
Hot Hand-Foot Syndrome
Body Piercing
Ecthyma Gangrenosum
Ear Infections
Simple Otitis Externa (Swimmer’s Ear)
Malignant Otitis Externa (Necrotizing Otitis Externa)
Eye Infections
Keratitis
Endophthalmitis
Urinary Tract Infections
Pseudomonas Species Other Than P. aeruginosa of Major Clinical Significance
Pseudomonas fluorescens
Pseudomonas fulva
Pseudomonas luteola
Pseudomonas mendocina
Pseudomonas mosselii
Pseudomonas oryzihabitans
Pseudomonas putida
Pseudomonas stutzeri
Novel Therapeutic Strategies Against P. aeruginosa Infections
Key References
References
220 Stenotrophomonas maltophilia and Burkholderia cepacia Complex
Short View Summary
Microbiology
Burkholderia cepacia Complex Species
Stenotrophomonas Genotypes
Pathogenesis
Lipopolysaccharides, Adhesion, and Invasion
Siderophores and Secreted Enzymes
Chronic Infection and Intracellular Survival
Biofilm and Quorum Sensing
Epidemiology and at-Risk Populations
Stenotrophomonas maltophilia
Burkholderia cepacia Complex
Clinical Manifestations
Stenotrophomonas maltophilia
Bacteremia and Endovascular Infections
Pulmonary Infections
Skin and Soft Tissue Infections
Head, Neck, and Central Nervous System Infections
Genitourinary, Abdominal, and Other Uncommon Infections
Burkholderia cepacia Complex
Respiratory Infections in Cystic Fibrosis
Lung Transplantation
Bacteremia and Pneumonia
Other Rare Manifestations
Therapy
Stenotrophomonas maltophilia
Burkholderia cepacia Complex
Prevention Strategies, Immunization, and Immunotherapy
Immunization and Immunotherapy
Key References
References
221 Burkholderia pseudomallei and Burkholderia mallei
Short View Summary
Melioidosis
History
Etiology
Epidemiology
Transmission
Pathogenesis
Clinical Manifestations
Laboratory Diagnosis
Therapy
Initial Intensive Therapy
Subsequent Eradication Therapy
Adjunctive Therapy
Prevention
Glanders
History
Etiology
Epidemiology, Transmission, and Pathogenesis
Clinical Manifestations
Laboratory Diagnosis
Therapy
Prevention
Key References
References
222 Acinetobacter Species
Short View Summary
Epidemiology
Health Care–Associated Infections
Community-Associated Infections
Diagnosis
Clinical Manifestations
Pathogenesis and Antimicrobial Resistance
Treatment
β-Lactam Antibiotics
β-Lactamase Inhibitors
Aminoglycosides
Tigecycline
Polymyxins
Combination Treatment
Prevention
Key References
References
223 Salmonella Species
Short View Summary
Classification and Taxonomy
The Genome
Microbiology
Epidemiology
Pathogenesis
Interactions With Intestinal Epithelium and Induction of Enteritis
Interactions With Macrophages and Systemic Infection
Host Response and Immunity
Clinical Manifestations
Gastroenteritis
Enteric Fever
Bacteremia and Vascular Infection
Salmonellosis and HIV Infection
Localized Infections
Chronic Carrier State
Immunization Against Salmonella
Therapy
Gastroenteritis
Bacteremia
Recurrent Salmonella Bacteremia in Persons With HIV
Focal Infections
Carrier State
Prevention and Control
Key References
References
224 Bacillary Dysentery
Short View Summary
Microbiology
Isolation Techniques
Group and Type Identification
Invasive Escherichia coli
Pathogenesis
Communicability and Infectivity
Mucosal Invasion and Inflammation
Toxigenicity
Anatomic Location of Infection
Epidemiology
Cyclic Patterns of Disease
Incidence of Shigellosis by Geography and Host
Modes of Spread and Reservoirs in Nature
Diagnosis
History
Physical Examination
Laboratory Findings
Therapy and Clinical Course
Control
Environmental Control
Immunologic Control
Key References
References
225 Haemophilus Species, Including H. influenzae and H. ducreyi (Chancroid)
Short View Summary
Haemophilus influenzae
Description of the Pathogen
Distinguishing Haemophilus influenzae from Haemophilus haemolyticus
Biotypes
Serotypes
Epidemiology and Respiratory Tract Colonization
Colonization in Children
Colonization in Adults With Chronic Obstructive Pulmonary Disease
Colonization and Conjugate Vaccines
Pathogenesis
Otitis Media
Otitis Media With Effusion
Biofilms
Exacerbations of Chronic Obstructive Pulmonary Disease
Invasive Infections Caused by Haemophilus influenzae Type b
Immunity
Nontypeable Haemophilus influenzae
Haemophilus influenzae Type b
Clinical Manifestations of Nontypeable Haemophilus influenzae
Otitis Media
Exacerbations of Chronic Obstructive Pulmonary Disease
Community-Acquired Pneumonia
Acute Respiratory Tract Infections in Children in Developing Countries
Sinusitis
Neonatal and Maternal Sepsis
Bacteremia and Invasive Infections
Conjunctivitis
Clinical Manifestations of Haemophilus influenzae Type b
Meningitis
Epiglottitis
Pneumonia and Empyema
Cellulitis
Bacteremia Without Localized Disease
Septic Arthritis
Clinical Manifestations of Non–Type b Encapsulated Haemophilus influenzae
Diagnosis
Nontypeable Haemophilus influenzae
Haemophilus influenzae Type b
Therapy
Nontypeable Haemophilus influenzae
Haemophilus influenzae Type b
Chemoprophylaxis for Haemophilus influenzae Type b
Active Immunization Against Haemophilus influenzae Type b
Haemophilus influenzae Biogroup aegyptius
Haemophilus ducreyi
Description of the Pathogen
Epidemiology
Pathogenesis and Immune Response
Clinical Manifestations
Diagnosis
Therapy
Other Haemophilus Species
Description of the Pathogens
Clinical Manifestations
Therapy
Key References
References
226 Brucellosis (Brucella Species)
Short View Summary
History
Microbiology
Epidemiology
Pathogenesis
Immune Response
Clinical Manifestations
Complications
Skeletal System
Nervous System
Genitourinary Tract
Cardiovascular System
Gastrointestinal System
Hepatobiliary System
Respiratory System
Hematologic Complications
Cutaneous Lesions
Ocular Lesions
Pregnancy
Diagnosis
Treatment
Prevention
Key References
References
227 Francisella tularensis (Tularemia)
Short View Summary
History
Microbiology
Virulence
Other Francisella Species
Epidemiology
Distribution
Incidence
Transmission
Pathogenesis
Immunity
Clinical Manifestations
Ulceroglandular and Glandular Tularemia
Oculoglandular Tularemia
Pharyngeal Tularemia
Typhoidal Tularemia
Pneumonic Tularemia
Secondary Skin Manifestations
Francisella tularensis subsp. novicida and Francisella philomiragia Infections
Clinical Recognition of a Bioterrorism Event
Complications and Outcome
Diagnosis
Routine Cultures and Pathology
Serologic Diagnosis
Investigational Diagnostic Assays
Therapy
Antibiotic Treatment
Pregnant and Immunosuppressed Patients
Surgical Treatment
Immunotherapy
Therapy for Tularemia After a Bioterrorism Event
Prevention
Vaccination
Antibiotic Prophylaxis
Antibiotic Prophylaxis After a Tularemia Bioterrorism Event
Key References
References
228 Pasteurella Species
Short View Summary
Description of the Pathogen
Epidemiology
Pathogenesis
Clinical Manifestations
Skin and Soft Tissue Infections
Bone and Joint Infections
Central Nervous System Infections
Bacteremia and Endocarditis
Respiratory Tract Infections
Intraabdominal Infections
Other Pasteurella Infections
Therapy, Prevention, and Prognosis
Key References
References
229A Plague (Yersinia pestis)
Short View Summary
History
Microbiology
Epidemiology
Natural Cycles
Transmission to Humans
Pathogenesis
Clinical Manifestations
Bubonic Plague
Septicemic Plague
Pneumonic Plague
Other Syndromes
Laboratory Findings
Diagnosis
Therapy
Antimicrobial Agents
Supportive Therapy
Prevention
Infection Control
Chemoprophylaxis
Vaccination
Environmental Control
Bioterrorism
Mass Prophylaxis
Occupational Exposure
Environmental Persistence
Acknowledgments
Key References
References
229B Yersinia enterocolitica and Yersinia pseudotuberculosis
Short View Summary
Microbiology
Epidemiology
Clinical Manifestations
Postinfectious Complications
Pathogenesis
Diagnosis
Treatment
Prevention
Acknowledgment
Key References
References
230 Bordetella pertussis
Short View Summary
History
Description of Pathogen
Pathogenesis
Epidemiology
Prevaccine Era
Vaccine Era
Current Issues Regarding Resurgence of Pertussis
Carrier State
Clinical Presentation
Young Children
Infants and Adults
Complications
Diagnosis
Culture
Molecular Diagnosis
Serology
Direct Fluorescent Antibody
Therapy
Antimicrobial Agents
Supportive Care
Prevention
Immunization
Acellular Pertussis Vaccines
Vaccination Schedules
Vaccination of Health Care Workers
Protection of Infants
Vaccination During Pregnancy
Neonatal Vaccination
Chemoprophylaxis
Pertussis in Schools and Daycare Centers
Future Directions
Key References
References
231 Rat-Bite Fever
Short View Summary
Streptobacillus Moniliformis
Bacteriology
Epidemiology
Pathophysiology
Clinical Manifestations
Diagnosis
Therapy and Prevention
Spirillum Minus
Bacteriology
Epidemiology, Pathogenesis, and Pathology
Clinical Manifestations
Diagnosis and Therapy
Key References
References
232 Legionnaires’ Disease and Pontiac Fever
Short View Summary
History
The Etiologic Agent
Microbial Ecology
Pathogenesis
Overview
Legionella pneumophila Virulence Factors
Virulence Factors and Pathogenesis of Other Legionella Species
Epidemiology
Incubation Period and Contagiousness
Patterns and Rates of Disease and Mortality
Risk Factors
Modes of Transmission
Outbreak Investigation
Environmental Decontamination for Outbreaks
Clinical Presentation
Legionnaires’ Disease
Extrapulmonary Infections
Pontiac Fever
Laboratory Diagnosis
Therapy and Response to Therapy
Prevention
Immunization and Chemoprophylaxis
Engineering Modifications and Maintenance
Environmental Cultures for Legionella Bacteria
Key References
References
233 Capnocytophaga
Short View Summary
Taxonomy
Pathogenesis and Clinical Manifestations
Human Oral-Associated Species
Infections Associated With Zoonotic Species
Epidemiology
Diagnosis and Laboratory Identification
Therapy
Prevention
Key References
References
234 Bartonella, Including Cat-Scratch Disease
Short View Summary
Background and Classification of Bartonella Species
Epidemiology of the Common Human-Pathogenic Bartonella Species
Bartonella bacilliformis Epidemiology
Bartonella quintana Epidemiology
Bartonella henselae Epidemiology
Epidemiology of Other Bartonella Species Associated With Human Infection
Clinical Manifestations of the Common Human Pathogenic Bartonella Species: B. Bacilliformis, B. Henselae, and B. Quintana (Table 234.2)
Bartonella Bacilliformis Clinical Manifestations: Oroya Fever and Verruga Peruana
Bartonella henselae and Bartonella quintana: Clinical Manifestations Depend on the Infecting Bartonella Species and Immune Status of Host
Bartonella henselae and Bartonella quintana: Bacteremic Illness
Bartonella henselae and Bartonella quintana: Endocarditis
Other Bartonella Species: Endocarditis and Bacteremia
Bartonella henselae and Bartonella quintana Infections in Immunocompromised Patients: Bacillary Angiomatosis/Bacillary Peliosis
Bartonella henselae: Cat-Scratch Disease
Cat-Scratch Disease Background
Typical Cat-Scratch Disease
Musculoskeletal Manifestations of Cat-Scratch Disease
Atypical Manifestations of Cat-Scratch Disease
Encephalopathy Complicating Cat-Scratch Disease
Ocular Manifestations of Cat-Scratch Disease
Differential Diagnosis of Cat-Scratch Disease
Bartonella Infections in Solid-Organ Transplant Recipients
Background/Risk Factors for Acquisition of Bartonella in Solid-Organ Transplant Recipients
Clinical Features of Bartonella Infection in Solid-Organ Transplant Recipients
Diagnosis of Bartonella Infections in Solid-Organ Transplant Recipients
Pathologic Findings and Relation to Duration of Time Posttransplant
Prognosis for Solid-Organ Transplant Recipients With Bartonella Infection
Cellular and Molecular Pathogenesis Associated With Bartonella Infections
Laboratory Diagnosis of Bartonella Infections
Direct Examination of Blood Smears and Histopathologic Specimens
Specimen Collection and Handling for Culture
Culture of Bartonella Species
Identification of Bartonella Species
Molecular Methods for Bartonella Identification and Characterization
Serologic Testing for Detecting Infection With Bartonella Species
Antimicrobial Susceptibility Testing of Bartonella Isolates
Treatment and Prevention of Bartonella Infections
Treatment of Bartonella bacilliformis Infections
Treatment of Bartonella Infections in the Immunocompromised Host
Treatment of Bartonella Bacteremia and Endocarditis
Treatment of Cat-Scratch Disease
Treatment of Neuroretinitis, Encephalopathy, Osteomyelitis, and Parenchymal Cat-Scratch Disease
Prevention of Bartonella Infections
Key References
References
235 Klebsiella granulomatis (Donovanosis, Granuloma Inguinale)
Short View Summary
Biology of Causative Organism
Geographic Distribution and Epidemiology
Clinical Manifestations
Diagnosis
Therapy
Acknowledgment
Key References
References
236 Other Gram-Negative and Gram-Variable Bacilli
Short View Summary
Glucose Fermenters
Actinobacillus and Aggregatibacter Species
Aeromonas Species
Cardiobacterium Species
Chromobacterium Species
Dysgonomonas Species
Kingella Species
Neisseria animaloris and Neisseria zoodegmatis
Plesiomonas shigelloides
Glucose Nonfermenters or Weak Fermenters
Achromobacter and Alcaligenes Species
Chryseobacterium and Elizabethkingia Species
Comamonas and Delftia Species
Eikenella Species
Flavobacterium and Myroides Species
Ochrobactrum Species
Oligella Species
Pseudomonas Species
Ralstonia and Cupriavidus Species
Rhizobium (Formerly Agrobacterium) Species
Roseomonas Species and Other “Pink-Pigmented” Gram-Negative Bacilli
Shewanella Species
Sphingobacterium Species
Sphingomonas Species
Weeksella and Bergeyella Species
Centers for Disease Control and Prevention Groups
Gardnerella and Mobiluncus Species
Key References
References
v. Spirochetes
237 Syphilis (Treponema pallidum)
Short View Summary
History
Etiology
Epidemiology
Pathogenesis
Pathologic Features
Natural Course of Untreated Syphilis
Clinical Manifestations
Primary Syphilis
Secondary Syphilis
Latent Syphilis
Tertiary Syphilis
Neurosyphilis
Asymptomatic Neurosyphilis
Syphilitic Meningitis
Meningovascular Syphilis
Parenchymatous Syndromes
Central Nervous System Gumma
Ocular Syphilis
Otosyphilis
Cardiovascular Syphilis
Late Benign (Gummatous) Syphilis
Laboratory Diagnosis
Direct Examination for Spirochetes
Darkfield Microscopy and Direct Fluorescent Antibody Test for Treponema pallidum
Visualization of Treponema pallidum in Tissues
Polymerase Chain Reaction Detection of Treponema pallidum
Serologic Tests
Nontreponemal Tests
Treponemal Tests
Syphilis Serologic Tests in HIV Infection
Rapid Point-of-Care Tests
Tests for Neurosyphilis
Therapy
Principles of Syphilotherapy
Incubating or Early Syphilis
Latency
Tertiary Syphilis
Cardiovascular and Gummatous Syphilis
Neurosyphilis
Penicillin Allergy
Gestational Syphilis
Jarisch-Herxheimer Reaction
Response to Therapy
Congenital Syphilis
Immunity
Acknowledgments
Key References
References
238 Endemic Treponematoses
Short View Summary
Microbiology
Morphology
Antibiotic Sensitivity
Epidemiology
Transmission
Clinical Manifestations
Late Complications and Sequelae
Differential Diagnosis
Yaws
Endemic Syphilis (Bejel)
Pinta
Attenuated Disease
Diagnosis
Direct Visualization
Serology
Point-of-Care Syphilis and Endemic Treponematosis Test
Polymerase Chain Reaction
Therapy
Prevention
Key References
References
239 Leptospira Species (Leptospirosis)
Short View Summary
History
Etiology
Epidemiology and Transmission
Pathogenesis
Clinical Manifestations
Laboratory Diagnosis
Direct Detection Methods
Isolation and Identification
Indirect Detection Methods
Therapy
Prevention
Key References
References
240 Relapsing Fever Caused by Borrelia Species
Short View Summary
Organism
Epidemiology and Transmission
Pathophysiology
Clinical Manifestations
Diagnosis
Therapy
Prevention
Borrelia miyamotoi
Key References
References
241 Lyme Disease (Lyme Borreliosis) Due to Borrelia burgdorferi
Short View Summary
Causative Organism
Vector of Transmission and Animal Hosts
Epidemiology
Pathogenesis
Clinical Characteristics
Early Infection: Stage 1 (Localized Infection)
Early Infection: Stage 2 (Disseminated Infection)
Late Infection: Stage 3 (Persistent Infection)
Post–Lyme Disease Symptoms or Syndrome
Congenital Infection
Coinfection
Laboratory Diagnosis
Differential Diagnosis
Therapy
Prevention
Key References
References
vi. Anaerobic Bacteria
242 Anaerobic Infections
Short View Summary
Definition of an Anaerobe
Anaerobes in the Normal Human Microbiota
The Microbiome in Health and Disease
Etiology and Microbiology of Anaerobic Clinical Infections
Anaerobic Gram-Negative Bacilli
Anaerobic Gram-Positive Cocci
Anaerobic Gram-Positive Non–Spore-Forming Rods
Anaerobic Spore-Forming Bacilli
Clinical Syndromes Caused by Anaerobes
Anaerobic Infections of the Mouth, Head, and Neck
Central Nervous System Infections
Pleuropulmonary Infections
Intraabdominal Infections
Female Genital Tract Infections
Skin and Soft Tissue Infections
Bone and Joint Infections
Anaerobic Bacteremia
Pathogenesis of Anaerobic Infections
Diagnosis of Anaerobic Infections
Treatment of Anaerobic Infections and Antibiotic Resistance
Acknowledgment
Key References
References
243 Clostridioides difficile (Formerly Clostridium difficile) Infection
Short View Summary
Historical Overview
Pathogenesis
The Indigenous Gut Microbiota and Antibiotics
Sporulation and Germination in Clostridioides difficile
Toxin Production
Other Virulence Factors
Host Response to Clostridioides difficile Infection
Pathogenesis of Recurrent Clostridioides difficile Infection
Altered Virulence in Specific Clostridioides difficile Lineages
Epidemiology
Health Care–Associated Clostridioides difficile Infection
Community-Associated Clostridioides difficile Infection
Molecular Epidemiology of Clostridioides difficile Infection and Importance of Strain Type
Clostridioides difficile Infection in Children
Risk Factors
Risk for Clostridioides difficile Infection
Risk for Recurrent Clostridioides difficile Infection
Risk for Severe Clostridioides difficile Infection
Infection Control and Prevention
Clinical and Pathologic Manifestations
Diagnosis
Treatment
Mild-to-Moderate Clostridioides difficile Infection
Severe Clostridioides difficile Infection
Severe Complicated or Fulminant Clostridioides difficile Infection
First Recurrence of Clostridioides difficile Infection
Multiple Recurrences of Clostridioides difficile Infection and Fecal Microbiota Transplantation
Monitoring Outcome of Treatment
Conclusions
Key References
References
244 Tetanus (Clostridium tetani)
Short View Summary
History
Epidemiology
Causes of Tetanus
Mortality
Microbiology of Clostridium Tetani
Pathogenesis
Clinical Manifestations
Diagnosis
Treatment
Stabilization
Management of Muscle Spasms
Wound Management
Passive Immunization
Antimicrobial Therapy
Management of Autonomic Dysfunction
Nutritional Support
Prevention
Key References
References
245 Botulism (Clostridium botulinum)
Short View Summary
History of Botulism
Epidemiology
Microbiology of Clostridium Botulinum
Pathogenesis
Clinical Manifestations
Diagnosis
Therapy
Prevention
Key References
References
246 Diseases Caused by Clostridium
Short View Summary
Characteristics of Clostridium Species
Microbiology
Pathogenesis
Major Infections and Intoxications
Clostridioides difficile Infection
Historical Perspective
Clinical Manifestations
Molecular Pathogenesis
Treatment and Diagnosis
CDI: an Emerging Public Health Crisis
Clostridium perfringens and Clostridial Myonecrosis (Gas Gangrene)
Pathogenesis
Diagnosis and Treatment
Clostridium botulinum and Botulism
Clostridium tetani and Tetanus
Food Poisoning Caused by Clostridium Species
Other Clostridial Infections
Bacteremia
Abdominal Infections
Biliary Tract Infections
Female Genital Tract Infections
Pleuropulmonary Infections
Key References
References
247 Bacteroides, Prevotella, Porphyromonas, and Fusobacterium Species (and Other Medically Important Anaerobic Gram-Negative Bacilli)
Short View Summary
Overview
History
Microbiology
Bacteroides
Prevotella and Porphyromonas
Fusobacterium
Symbiosis
Gastrointestinal Tract
Symbiosis and Mutualism in Immunity and Metabolism
Female Urogenital Tract
Oropharynx
Opportunism
Endotoxic Lipopolysaccharide
Capsular Polysaccharides
Pili and Fimbriae
Enzymes and Toxins
Metabolic End Products
Host Immune Response
Infections
Bacteremia
Skeletal Infection
Skin and Soft Tissue Infection
Central Nervous System Infection
Infections of the Aerodigestive Tract
Oropharyngeal Infections
Salivary Gland Infections
Ear Infections
Thoracic Infections
Cardiovascular Infections
Intraabdominal Infections
Peritonitis
Enteritis
Urogenital Tract Infections
Recent Associations of Gram-Negative Anaerobic Rods and Disease
Therapy
Surgical Treatment
Antibiotic Therapy
Key References
References
248 Anaerobic Cocci and Anaerobic Gram-Positive Nonsporulating Bacilli
Short View Summary
Taxonomy
Members of the Commensal Microbiota
Clinical Significance
Gram-Positive Anaerobic Cocci
Anaerococcus
Finegoldia
Parvimonas
Peptoniphilus
Peptostreptococcus
Murdochiella
Ruminococcus
Gram-Negative Anaerobic Cocci
Acidaminococcus
Anaeroglobus
Megasphaera
Negativicoccus
Veillonella
Gram-Positive Anaerobic Nonsporulating Rods
Propionibacteria
Lactobacilli
Bifidobacteria
Atopobium and Olsenella
Actinomyces-Like Organisms
Mobiluncus
Eggerthella and Related Species
Eubacterium and Related Taxa
Microbiologic Aspects
Treatment
Key References
References
vii. Mycobacterial Diseases
249 Mycobacterium tuberculosis
Short View Summary
History
Microbiology
Acid-Fast Staining
Culture Methods for Mycobacterium tuberculosis
Nucleic Acid Amplification
Detection of Mycobacterial Antigens in Urine
Speciation of Mycobacteria
Genotyping of Mycobacterium tuberculosis
Drug Susceptibility Testing
Epidemiology
General Considerations
Recent Morbidity and Mortality Trends
Drug-Resistant Tuberculosis
Mode of Spread
Risk for Infection
Influence of Chemotherapy on Spread of Infection
Risk for Progression From Infection to Active Disease
Institutional Spread of Tuberculosis
Hospitals
Shelters for the Homeless
Correctional Facilities
Controlling Nosocomial Spread
Immunology
Testing for Latent Tuberculosis Infection
Tuberculin Skin Test
Dosage
Technical Aspects
Targeted Tuberculin Testing
Interpretation
Booster Effect
False-Positive and False-Negative Reactions
Variant (“Delayed”) Tuberculin Reactivity
Loss of Tuberculin Reactivity
Tuberculin Skin Testing and HIV Infection
Interferon-γ Release Assays for Latent M. tuberculosis Infection
Pathogenesis
Evolution of the Primary Infection
Primary (Childhood) and Reinfection (Adult) Tuberculosis
Chronic Pulmonary Tuberculosis
Apical Localization
Endogenous Versus Exogenous Reinfection
Influence of Age on Tuberculous Infection
Infection in Infancy and Childhood
Infection in Adolescence and Young Adulthood
Infection in Midadulthood
Infection in Old Age
Late Hematogenous Tuberculosis
Intercurrent Events
Tuberculosis in People With HIV Infection
Pulmonary Tuberculosis
Primary Tuberculosis in Childhood
Postprimary (Adult-Type) Pulmonary Tuberculosis
Lower Lobe and Endobronchial Tuberculosis
Progressive Lower Lobe Disease in Older Persons
Endobronchial Tuberculosis
Pulmonary Tuberculosis in AIDS
Tuberculomas
Symptoms
Physical Examination
Radiographic Findings
Laboratory Findings
Diagnosis
Fiberoptic Bronchoscopy
Tuberculosis Diagnosed at Autopsy
Tuberculosis and Cancer
Therapy
Antituberculous Drugs
Isoniazid
Rifampin
Rifapentine
Pyrazinamide
Ethambutol
Streptomycin
Fluoroquinolones
Bedaquiline
Second-Line Agents
Third-Line Agents
Agents Under Development
Selecting a Drug Regimen
Standard Regimens Based on Isoniazid and Rifampin
Directly Observed Treatment
Regimens of Less Than 6 Months for Minimal Disease
Fixed-Dose Combination Tablets
Treatment of Multidrug-Resistant Tuberculosis
Therapy for Extensively Drug-Resistant Tuberculosis
Course of Therapy and Duration of Observation
Retreatment
Other Forms of Treatment
Corticosteroids
Treatment of Tuberculosis in HIV-Infected Patients
Immune Reconstitution Inflammatory Syndrome
Duration of Therapy
Other Special Treatment Circumstances
Childhood
Pregnancy
Uremia and End-Stage Renal Disease
Liver Disease
Patients Receiving Immunosuppressive Drugs
Treatment of Latent Tuberculous Infection
Drug Regimens
Risk for Isoniazid Hepatotoxicity During Treatment of Latent Tuberculous Infection
Treatment of Contacts of Active Cases
Treatment of Quiescent, Previously Untreated Pulmonary Tuberculosis
Treatment of Individuals With Recent Infection
Treating Latent Tuberculous Infection in Persons With HIV Infection
Mycobacterium tuberculosis Infection in Persons With Additional Risk Factors
Pregnant Women
The Nursing Home Problem
Vaccination
Extrapulmonary Tuberculosis
AIDS and Extrapulmonary Tuberculosis
General Comments on Treatment of Extrapulmonary Tuberculosis
Miliary Tuberculosis
Usual (Acute) Miliary Tuberculosis
Cryptic Miliary Tuberculosis and Late Generalized (Chronic Hematogenous) Tuberculosis
Nonreactive Tuberculosis
Miliary Tuberculosis and Hematologic Abnormalities
Primary Hepatic Tuberculosis
Miliary Tuberculosis in AIDS
Central Nervous System Tuberculosis: Tuberculous Meningitis
Pathologic Features
Clinical Manifestations
Therapy
Tuberculomas
Tuberculous Spinal Meningitis
Tuberculous Pleurisy (Serofibrinous Pleurisy With Effusion)
Types of Tuberculous Pleurisy
Early Postprimary Pleurisy With Effusion
Pleurisy With Effusion Complicating Chronic Pulmonary Tuberculosis
Pleurisy With Effusion Complicating Miliary Tuberculosis
Clinical Manifestations and Diagnosis
Therapy
Tuberculous Empyema and Bronchopleural Fistula
Tuberculous Pericarditis
Clinical Manifestations and Diagnosis
Therapy
Skeletal Tuberculosis: Pott Disease (Tuberculous Spondylitis)
Clinical Manifestations
Abscess and Sinus Formation
Spinal Tuberculosis Without Bony Involvement on Plain Films
Pott Paraplegia
Therapy
Peripheral Osteoarticular Tuberculosis
Genitourinary Tuberculosis: Renal Tuberculosis
Male Genital Tuberculosis
Genitourinary Tuberculosis in AIDS
Female Genital Tuberculosis
Gastrointestinal Tuberculosis
Gastrointestinal Tuberculosis in AIDS
Tuberculous Peritonitis
Tuberculous Lymphadenitis (Scrofula): Peripheral Nodes
Mediastinal Tuberculous Lymphadenopathy
Fibrosing Mediastinitis
Mesenteric Tuberculous Lymphadenitis
Cutaneous Tuberculosis
Tuberculous Laryngitis
Tuberculous Otitis
Miscellaneous Conditions
Mycobacterium bovis and Bacillus Calmette-Guérin
Key References
References
250 Leprosy (Mycobacterium leprae)
Short View Summary
History and Society
Epidemiology
Genetic Epidemiology
Zoonotic Potential
Nosocomial Infections
Global Epidemiology
Epidemiology in the United States
Microbiology
Mechanisms of Immunity
Clinical Manifestations of Leprosy
Clinical Presentation
Diagnostic Testing
Treatment of Leprosy
Antibiotics
Drug Resistance
Surgical Intervention
Physical Therapy and Occupational Therapy Interventions
Monitoring Treatment Response
Prevention of Leprosy
Pathologic Immune Reactions of Leprosy
Type 1 Reversal Reaction
Neuritis
Type 2 Erythema Nodosum Leprosum
Necrotic Vasculitis (Lucio Phenomenon)
Considerations for People With Altered Immunity
Key References
References
251 Mycobacterium avium Complex
Short View Summary
Epidemiology
Reservoir and Route of Acquisition
Pulmonary Disease
Extrapulmonary Disease
Pathogen: Classification and Microbiology
Organisms
Virulence
Pathogenesis
Pulmonary Disease
Extrapulmonary Disease
Host Immunity
Pulmonary Disease
Extrapulmonary Disease
Clinical Manifestations
Pulmonary Disease
Extrapulmonary Disease
Diagnosis
Pulmonary Disease
Extrapulmonary Disease
Treatment and Prevention
Principles of Treatment
Specific Antimicrobials
Antimicrobial Tolerability
Drug Interactions
Drug Dosing in Impaired Renal Function
Serum Drug Level Monitoring
Macrolide-Resistant Mycobacterium avium Complex Disease
Immunomodulatory Treatment of Mycobacterium avium Complex Disease
Specific Organ System Treatment Considerations
Pulmonary Mycobacterium avium Complex
Treatment Choice and Monitoring
Surgery
Hypersensitivity Pneumonitis
Extrapulmonary Disease
Disseminated Disease
Prevention.
Other Localized Disease
Key References
References
252 Infections Caused by Nontuberculous Mycobacteria Other Than Mycobacterium avium Complex
Short View Summary
Overview
Rapidly Growing Mycobacteria
Slowly Growing Mycobacteria
Intermediately Growing Mycobacteria
Nontuberculous Mycobacteria and the Environment
Nontuberculous Mycobacteria and Clinical Disease
Pulmonary Disease
Geography of Common Nontuberculous Mycobacteria Species
Nontuberculous Mycobacteria Species Associated Infrequently With Pulmonary Disease
Pulmonary Syndromes Associated With Nontuberculous Mycobacteria Other Than Mycobacterium avium Complex
Clinical Presentation of Nontuberculous Mycobacterial Lung Disease
Treatment of Mycobacterium avium Complex Lung Disease
Treatment of Mycobacterium kansasii Lung Disease
Treatment of Mycobacterium abscessus subsp. abscessus and Mycobacterium abscessus subsp. massiliense Lung Disease
Treatment of Other Nontuberculous Mycobacterial Lung Disease
Lymphadenitis
Localized Cutaneous, Joint, and Soft Tissue Infections
Intermediately Growing Mycobacteria
Mycobacterium marinum
Community-Acquired Extrapulmonary Infections Due to Rapidly Growing Mycobacteria
Slowly Growing Mycobacteria
Health Care–Associated Infections
Skin/Soft Tissue
Diagnosis and Treatment
Infection of Tendon Sheaths, Bones, Bursae, and Joints
Disseminated Disease
Catheter-Related Infections
Miscellaneous Infections
Laboratory Aspects
Stain and Culture
Identification
Susceptibility Testing: Rapidly Growing Mycobacteria
Susceptibility Testing: Slowly Growing Nontuberculous Mycobacteria
Strain Comparison
Key References
References
viii Higher Bacterial Diseases
253 Nocardia Species
Short View Summary
Classification
Molecular Identification and Taxonomy
Ecology and Epidemiology
Pathology
Pathogenesis
Immune Response to Nocardia Infection
Specific Virulence Determinants
Host Cell–Nocardia Interactions
Biofilms
Clinical Epidemiology
Nocardia Species and Disease Associations
Immunocompromise as a Risk Factor for Nocardiosis
Chronic Lung Disease as a Risk Factor for Nocardiosis
Clinical Manifestations
Primary Cutaneous Nocardiosis
Pulmonary Disease
Radiologic Manifestations of Pulmonary Nocardiosis
Differential Diagnosis of Pulmonary Nocardiosis
Central Nervous System Nocardiosis
Disseminated Nocardiosis
Keratitis
Colonization
Laboratory Diagnosis
Identification of Nocardia Species
Management
Antimicrobial Selection
In Vitro Susceptibility Testing
Antimicrobial Regimens
Trimethoprim-Sulfamethoxazole
Other Regimens
Amikacin and Carbapenems
Third-Generation Cephalosporins
Oxazolidinones: Linezolid and Tedizolid
Minocycline and Amoxicillin-Clavulanate
Fluoroquinolones, Macrolides, and Tigecycline
Superficial Infection and Mycetoma
Nocardia Intravascular Catheter-Related Bloodstream Infection
Severe Infection
Empirical Therapy
Surgical Management
Surgery in Extraneural Nocardiosis
Surgery in Cerebral Nocardiosis
Keratitis and Other Eye Infections
Keratitis
Endophthalmitis
Duration of Therapy and Prognosis
Clinical Responses to Therapy
Causes of Therapeutic Failure
Management of Immunosuppressive Drug Therapy in Patients With Nocardiosis
Duration of Therapy in Immunocompetent Hosts
Duration of Therapy in Immunosuppressed Hosts
Short-Course Therapy
Prophylaxis
Primary Prophylaxis
Secondary Prophylaxis
Clinical Outcomes
Effect of Nocardia Species on Outcome
Summary of Management
Key References
References
254 Agents of Actinomycosis
Short View Summary
Etiologic Agents
Epidemiology
Pathogenesis and Pathology
Clinical Manifestations
Oral-Cervicofacial Disease
Thoracic Disease
Endocarditis, Pericarditis, and Mediastinal Disease
Abdominal Disease
Pelvic Disease
Central Nervous System Disease
Musculoskeletal Disease
Disseminated Disease
Diagnosis
Therapy
Key References
References
G Mycoses
255 Introduction to Mycoses
Changes in How Fungi Are Identified
Identification by DNA Sequence
Cryptic Species
One Fungus, One Name
Common Features of Pathogenic Fungi
Yeasts and Molds
Dimorphic Fungi
Diagnosis of Mycoses
Microscopic Appearance of Fungi
Tissue Stains
Fresh Clinical Specimens
Serologic Diagnosis
Epidemiology
References
256 Candida Species
Short View Summary
Pathogen
Epidemiology and Ecology
Pathogenesis and Immunology
Clinical Manifestations
Mucous Membrane Infections
Thrush
Candida Esophagitis
Nonesophageal, Mucous Membrane, Gastrointestinal Candidiasis
Candida Vaginitis
Cutaneous Candidiasis Syndromes
Generalized Cutaneous Candidiasis
Erosio Interdigitalis Blastomycetica
Candida Folliculitis
Candida Balanitis
Cutaneous Lesions of Disseminated Candidiasis
Intertrigo
Paronychia and Onychomycosis
Diaper Rash
Perianal Candidiasis
Chronic Mucocutaneous Candidiasis
Deep Organ Involvement
Central Nervous System Candidiasis
Respiratory Tract Candidiasis
Cardiac Candidiasis
Candida Endocarditis
Urinary Tract Candidiasis
Candida Arthritis, Osteomyelitis, Costochondritis, and Myositis
Intraabdominal Candidiasis: Candida Infection of Peritoneum, Liver, Spleen, and Gallbladder
Candidemia
Ocular Candidiasis
Endogenous Ocular Candidiasis
Exogenous Ocular Candidiasis
“Chronic Candidiasis Syndrome” or “the Yeast Connection”
Treatment and Prophylaxis
General Comments
Systemic Drugs for Candidiasis
Polyenes
Triazoles
Echinocandins
Flucytosine
Candidemia in Nonneutropenic Patients
Candidemia in Neutropenic Patients
Candida Infections of the Cardiovascular System
Central Nervous System Candida Infection
Intraabdominal Candidiasis, Candida Peritonitis, Gallbladder Infection
Urinary Candidiasis
Mucocutaneous Candidiasis
Chronic Mucocutaneous Candidiasis
Ocular Candidiasis
Key References
References
257 Aspergillus Species
Short View Summary
Mycology
Epidemiology
Pathogenicity and Host Defenses
Clinical Presentation
Allergic Manifestations of Disease
Allergic Bronchopulmonary Aspergillosis
Other Allergic Manifestations
Saprophytic Colonization and Superficial Aspergillosis
Fungus Balls Due to Aspergillus
Other Superficial or Colonizing Syndromes of Aspergillosis
Invasive Syndromes Caused by Aspergillus
Invasive Pulmonary Aspergillosis
Tracheobronchitis
Sinusitis
Disseminated Infection
Other Invasive Syndromes
Cerebral Aspergillosis
Bone Aspergillosis
Cutaneous Infection
Other Sites
Diagnosis and Antifungal Resistance
Therapy (Table 257.4)
Primary Antifungal Therapy
Voriconazole
Alternative Primary Therapy
Isavuconazole
Lipid Amphotericin Formulations
Other Antifungal Agents
Amphotericin B Deoxycholate
Other Polyenes
Other Triazoles
Echinocandins
Combination Antifungal Therapy
Adjuvant Therapy
Approach to Therapy
Prevention and Prophylaxis
Key References
References
258 Agents of Mucormycosis and Entomophthoramycosis
Short View Summary
Etiology
Insights From Genomic Sequencing
Acquisition of Infection
Patient Populations at Risk
Incidence of Mucormycosis
Pathogenesis (Fig. 258.3)
Role of Iron Uptake in Mucormycosis Pathogenesis
Host Immune Response Against Mucormycosis
Histopathology
Clinical Manifestations of Mucormycosis
Rhinocerebral Infections
Clinical Presentation
Radiology
Pulmonary Infections
Clinical Presentation
Radiology
Pulmonary Mucormycosis in Less Severely Immunocompromised Patients
Skin and Soft Tissue Infections
Osteomyelitis
Gastrointestinal Mucormycosis
Disseminated Mucormycosis
Less Common Presentations of Mucormycosis
Diagnosis
Species Identification
Differentiating Mucormycosis From Other Molds
Antifungal Susceptibility Testing
Combination Therapy
Treatment
Antifungal Therapy
Lipid Amphotericin B Formulations
Triazoles
Combination Therapy
Treatment Duration
Prophylaxis
Surgical Management
Adjunctive Therapies
Prognosis
Entomophthoramycosis
Conidiobolomycosis
Basidiobolomycosis
Diagnosis
Differential Diagnosis
Therapy and Prevention
Key References
References
259 Sporothrix schenckii
Short View Summary
Mycology
Epidemiology
Clinical Syndromes
Lymphocutaneous Sporotrichosis
Extracutaneous Sporotrichosis
Multifocal Extracutaneous Sporotrichosis
Clinical Manifestations of Sporotrichosis in the HIV-Infected Patient
Diagnosis
Therapy
Therapy of Patients With Acquired Immunodeficiency Syndrome
Itraconazole Blood Level Monitoring
Prognosis
Key References
References
260 Agents of Chromoblastomycosis
Short View Summary
Etiologic Agents
Epidemiology
Pathology and Pathogenesis
Clinical Manifestations
Diagnosis
Therapy
Key References
References
261 Agents of Mycetoma
Short View Summary
Etiologic Agents
Epidemiology
Pathology and Pathogenesis
Clinical Manifestations
Diagnosis
Therapy
Prevention
Key References
References
262 Cryptococcosis (Cryptococcus neoformans and Cryptococcus gattii)
Short View Summary
History
Mycology
Life Cycle and Genetics
Taxonomy
Identification
Ecology
Cryptococcus neoformans Serotypes A, D, and AD (grubii var. or neoformans var.)
Cryptococcus gattii Serotypes B and C
Epidemiology
Pathogenicity
Capsule
Melanin
High-Temperature Growth
Other Pathogenicity Factors
Host Responses
Pathogenesis
Clinical Manifestations
Lung
Central Nervous System
Skin
Prostate
Eye
Other Body Sites
Immune Reconstitution Inflammatory Syndrome
Laboratory Diagnosis
Microscopic Examination
Cultures
Antigen Detection
Radiology
Management
In Vitro Drug Susceptibility Analysis
Treatment Strategies
Cryptococcal Meningitis
Prognosis
Prevention
Key References
References
263 Histoplasma capsulatum (Histoplasmosis)
Short View Summary
History
Ecology and Epidemiology
Mycology
Pathogenesis
Innate Immunity
Adaptive Immunity
Genetic Predisposition to Disease
Granulomas
Delayed-Type Hypersensitivity
Pulmonary Histoplasmosis
Acute Infections
Acute Primary Infection
Symptoms
Clinical Findings
Pericarditis
Differential Diagnosis
Acute Reinfection
Complications of Primary Histoplasmosis
Histoplasmoma
Mediastinal Granuloma and Fibrosis
Chronic Pulmonary Histoplasmosis
Symptoms
Laboratory Findings
Pathology
Noncavitary Chronic Pulmonary Disease
Progressive Disseminated Histoplasmosis
Incidence
Reactivation Versus New Exposure
Pathology
Acute Progressive Disseminated Histoplasmosis
Laboratory Abnormalities
Progressive Disseminated Histoplasmosis and HIV
Laboratory Abnormalities in Coinfection
Subacute Progressive Disseminated Histoplasmosis
Clinical Features
Endovascular Infection
Central Nervous System Involvement
Chronic Progressive Disseminated Histoplasmosis
Clinical Findings
Ocular Histoplasmosis
African Histoplasmosis
Diagnosis
Fungal Culture
Antigen Detection
Serology
Histochemical Identification
Miscellaneous Laboratory Tests
Therapy
Acute Pulmonary Histoplasmosis
Mediastinal Granuloma, Mediastinal Fibrosis, and Histoplasmoma
Cavitary Pulmonary Histoplasmosis
Acute Progressive Disseminated Histoplasmosis
Subacute and Chronic Progressive Disseminated Histoplasmosis
Meningitis
Endocarditis
Pericarditis
Arthropathies
Presumed Ocular Histoplasmosis
Other Considerations
Immune Reconstitution Syndrome and Histoplasma
Prevention
Prophylaxis of Immunocompromised Persons
Other Considerations
Key References
References
264 Blastomycosis
Short View Summary
History
Mycology
Geographic Distribution and Ecology
Epidemiology
Pathogenesis, Virulence, and Host Defense
Clinical Manifestations
Pulmonary Blastomycosis
Disseminated Blastomycosis
Blastomycosis in Immunocompromised Patients
Pregnancy
Diagnosis
Treatment
Acknowledgment
Key References
References
265 Coccidioidomycosis (Coccidioides Species)
Short View Summary
Mycology
Mycelial (Saprobic) Growth
Spherule (Parasitic) Growth
Epidemiology
Geographic Range
Rates of Coccidioidal Infection
Pathogenesis and Control
Histopathology
Host Defenses
Clinical Manifestations
Early Respiratory Infection
Pulmonary Nodules and Cavities
Chronic Fibrocavitary Pneumonia
Extrapulmonary Dissemination
Diagnosis
Direct Examination and Culture
Serologic Testing
Tube Precipitin Antibodies
Complement-Fixing Antibodies
Immunodiffusion Tests
Enzyme-Linked Immunoassays
Latex Tests
Skin Testing
Coccidioidal Antigen Detection
Management
General Approaches
Therapy
Early Uncomplicated Infections
Diffuse Pneumonia
Pulmonary Cavity
Chronic Fibrocavitary Pneumonia
Extrapulmonary Dissemination
New Therapies
Prevention
Key References
References
266 Dermatophytosis (Ringworm) and Other Superficial Mycoses
Short View Summary
Dermatophytosis
Dermatophytes
Epidemiology
Zoophilic Dermatophyte Infections
Geophilic Dermatophyte Infections
Anthropophilic Dermatophyte Infections
Age Incidence
Pathogenesis
Clinical Manifestations
Tinea Pedis
Tinea Cruris
Tinea Corporis
Tinea Imbricata
Tinea Manuum
Tinea Faciei
Tinea Capitis
Onychomycosis Caused by Dermatophytes
Deep Dermatophyte Infections
Dermatophyte “Id” Reactions
Point of Care and Laboratory Diagnosis
Therapy
Ringworm of the Glabrous Skin (Tinea Pedis, Corporis, Manuum)
Topical Therapy
Systemic Therapy
Tina Capitis
Onychomycosis
Neoscytalidium Infections
Clinical Manifestations
Diagnosis
Therapy
Other Forms of Onychomycosis
Pityriasis Versicolor
Organisms
Pathogenesis
Clinical Manifestations
Therapy
Other Malassezia Infections
Malassezia Folliculitis
Seborrheic Dermatitis
Clinical Manifestations
Therapy
Tinea Nigra
White Piedra
Black Piedra
Key References
References
267 Paracoccidioidomycosis
Short View Summary
Description of the Pathogen
Ecology and Epidemiology
Pathogenesis and the Immune Response
Innate Immune Responses
Acquired Immune Responses
Humoral Immune Responses
Immunoregulation, Immunomodulation, and Vaccines
Clinical Manifestations
Characteristics of the Lesions
Lungs
Mucosa
Skin
Lymph Nodes
Adrenal Glands
Other Lesions
Paracoccidioidomycosis in Human Immunodeficiency Virus–Infected Patients
Paracoccidioidomycosis and Cancer
Differential Diagnosis
Treatment
Sulfonamides
Amphotericin B
Azole Derivatives
Immune Stimulation
Criteria of Recovery
Laboratory Diagnosis
Direct Examination
Histopathology
Cultures
Immune-Based Diagnostic Tests
Molecular Testing
Skin Tests
Key References
References
268 Uncommon Fungi and Related Species
Short View Summary
Scedosporium Apiospermum (Pseudallescheria Boydii) Species Complex
Lomentospora (Formerly Scedosporium) Prolificans
Dark-Walled Fungi and Agents of Phaeohyphomycosis
Fusarium Spp.
Other Opportunistic Molds
Trichosporon Spp.
Malassezia Furfur
Other Uncommon Yeasts
Talaromyces (Formerly Penicillium) Marneffei
Lacazia Loboi
Agents of Adiaspiromycosis (Emmonsia Spp.)
Emergomyces Africanus and Other Emergomyces Species
Prototheca Spp.
Pythium Spp.
Rhinosporidium Seeberi
Summary
Key References
References
269 Pneumocystis Species
Short View Summary
Pathogen
Epidemiology
Pathology and Pathogenesis
Clinical Manifestations
Other Clinical Manifestations
Diagnosis
Granulomatous Pneumocystosis
Course and Prognosis
Treatment
Prevention
Chemoprophylaxis
Stopping Prophylaxis
Prophylaxis of PCP Among Patients With Non–HIV-Associated Immunosuppression
Boosting Host Immune Response
Preventing Exposure
Key References
References
270 Microsporidiosis
Short View Summary
General Characteristics
Phylogeny of the Microsporidia
Epidemiology
Immunology
Pathology and Pathogenesis
Gastrointestinal Tract Infections
Genitourinary Tract Infection
Central Nervous System Infection
Ocular Infection
Musculoskeletal Infection
Sinus and Respiratory Infection
Skin
Clinical Manifestations
Microsporidian Infection in Non-AIDS Patients
Microsporidian Infection in AIDS Patients
Enterocytozoonidae
Encephalitozoonidae
Other Microsporidia
Diagnosis
Therapy
Gastrointestinal and Systemic Disease
Ocular Disease
Prevention
Key References
References
H Protozoal Diseases
271 Introduction to Protozoal Diseases
Key References
References
272 Entamoeba Species, Including Amebic Colitis and Liver Abscess
Short View Summary
Organism
Species of Entamoeba
Genotypes of Entamoeba histolytica
Life Cycle
Metabolism
Cell Biology
Genome Structure
Pathogenesis
Adherence
Cytolysis
Phagocytosis
Role of Bacteria
Cysteine Proteinases
Role of Leptin in Host Resistance
Macrophage Migration Inhibitory Factor and Inflammation
Immune Response and Immunity
Innate Immunity
Neutrophils and Eosinophils
Macrophages
Natural Killer Cells and Natural Killer T Cells
Activated Mast Cells
Complement-Mediated Lysis of Entamoeba histolytica
Intestinal Epithelial Cells
Acquired Immunity
Mucosal Immunoglobulin A Response
Cell-Mediated Response
Epidemiology
Clinical Manifestations
Asymptomatic Intraluminal Amebiasis
Amebic Diarrhea
Amebic Dysentery or Colitis
Amebic Liver Abscess
Metastatic Amebiasis
Diagnosis
Stool Ova and Parasite Examination
Culture
Antigen Testing for Amebiasis
Polymerase Chain Reaction Testing for Amebiasis
Serologic Tests for Amebiasis
Colonoscopy and Biopsy
Imaging
Therapy
Noninvasive Infections
Invasive Infections
Prevention
Key References
References
273 Free-Living Amebae
Short View Summary
Organisms
Naegleria
Acanthamoeba
Balamuthia
Other Free-Living Amebae Reported in Human Disease
Epidemiology
Naegleria
Acanthamoeba
Balamuthia
Pathogenesis and Pathologic Findings
Naegleria
Acanthamoeba
Balamuthia
Clinical Manifestations
Naegleria
Acanthamoeba
Balamuthia
Laboratory Diagnosis
Naegleria
Acanthamoeba
Balamuthia
Treatment
Naegleria
Clinical Evidence
Animal Models and In Vitro Assays
Recommendations
Acanthamoeba Granulomatous Amebic Encephalitis and Disseminated Disease
Clinical Evidence
Animal Models and In Vitro Assays
Recommendations
Acanthamoeba Keratitis
Recommendations
Balamuthia
Clinical Evidence
In Vitro Assays
Recommendations
Prevention
Resources
Key References
References
274 Malaria (Plasmodium Species)
Short View Summary
The Malaria Problem
Plasmodium and Its Life Cycle
Pathophysiology
The Malaria Paroxysm and General Considerations
Plasmodium falciparum
Cerebral Malaria
Hypoglycemia
Anemia
Pulmonary Edema and Respiratory Distress
Metabolic (Lactic) Acidosis
Malaria of Pregnancy
Plasmodium vivax and Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi
Genetic Resistance to Malaria
Hemoglobins S, C, and E
Thalassemias
Hemoglobin F
Glucose-6-Phosphate Dehydrogenase Deficiency
Southeast Asian Ovalocytosis and Hereditary Xerocytosis
ABO Blood Groups
Duffy Antigen Receptor for Chemokines Negativity
Acquired Immunity and Antigenic Variation
Epidemiology of Malaria
Distribution of Drug Resistance
Antimalarial Drugs: Mechanisms of Action and Resistance
Chloroquine
Amodiaquine
Piperaquine
Sulfadoxine-Pyrimethamine
Atovaquone-Proguanil (Malarone)
Doxycycline
Mefloquine, Quinidine, Quinine
Artemisinin Derivatives
Clinical Presentation and Diagnosis of Malaria
History and Physical Examination
Thick and Thin Blood Smears
Rapid Diagnostic Tests
Other Laboratory Tests
Severe P. falciparum Malaria
Distinguishing Malaria From Other Illnesses With Similar Clinical Presentations
Influenza
Enteric Fever
Bacteremia/Sepsis
Dengue Fever
Acute Schistosomiasis (Katayama Fever)
Leptospirosis
African Tick Fever
East African Trypanosomiasis (Sleeping Sickness)
Yellow Fever
Therapy (see also Chapter 41)
General Principles
Uncomplicated Malaria
Chloroquine Phosphate
Atovaquone-Proguanil (Malarone)
Artemisinin-Based Combination Therapies
Quinine Plus Doxycycline
Mefloquine
Standby Emergency Treatment of Uncomplicated Malaria in Travelers
Intermittent Presumptive Treatment in Infants, Children, and Pregnant Women
Seasonal Malaria Chemoprevention
Mass Drug Administration
Severe Malaria
Quinidine Gluconate
Artemisinin and Its Derivatives
Quinine Dihydrochloride
Bacteremia and Sepsis in Severe Malaria
Exchange Transfusion in Severe Malaria
Nonfalciparum Malaria
Prevention
Risk Assessment
Chemoprophylaxis
Areas With Chloroquine-Sensitive Malaria
Areas With Mefloquine-Sensitive Malaria
All Areas
Mosquito Repellent and Avoidance Measures
Vaccination
Key References
References
275 Leishmania Species
Short View Summary
Overview and General Principles
Life Cycle and Morphology
Taxonomy and Classification
Transmission Principles and Sand Fly Biology
Pathogenesis and Immunology
Diagnostic Principles
Treatment Principles
Visceral Leishmaniasis
Epidemiology
Pathogenesis and Immunology
Natural History and Latent Visceral Leishmaniasis Infection
Clinical Manifestations
Diagnosis
Visceral Leishmaniasis in Immunocompromised Patients
Post–Kala-Azar Dermal Leishmaniasis
Treatment
Liposomal Amphotericin B and Other Formulations
Pentavalent Antimony
Miltefosine
Paromomycin
Combination Therapy for Visceral Leishmaniasis
Treatment and Secondary Prophylaxis of Visceral Leishmaniasis in Immunocompromised Hosts
Treatment of Post–Kala-Azar Dermal Leishmaniasis
Cutaneous Leishmaniasis
Epidemiology
Pathogenesis and Immunology
Clinical Manifestations of New World and Old World Cutaneous Leishmaniasis
Diffuse Cutaneous Leishmaniasis
Leishmaniasis Recidivans
Disseminated Leishmaniasis
Diagnosis
Treatment
Old World Cutaneous Leishmaniasis
New World Cutaneous Leishmaniasis
Pentavalent Antimony
Liposomal Amphotericin B
Pentamidine
Azoles
Miltefosine
Mucosal Leishmaniasis
Epidemiology
Pathogenesis and Immunology
Clinical Manifestations
Diagnosis
Treatment
Prevention
Key References
References
276 Trypanosoma Species (American Trypanosomiasis, Chagas Disease)
Short View Summary
Chagas Disease
Life Cycle and Transmission
Pathology
Epidemiology
Clinical Manifestations
Immunosuppression and Transplantation in T. Cruzi–Infected Patients
Diagnosis
Therapy
Prevention
Key References
References
277 Agents of African Trypanosomiasis (Sleeping Sickness)
Short View Summary
Parasites and Their Transmission
Pathogenesis and Pathology
Epidemiology
West African Trypanosomiasis
East African Trypanosomiasis
Clinical Course
West African Trypanosomiasis
East African Trypanosomiasis
Diagnosis
Therapy
Prevention
Key References
References
278 Toxoplasma gondii
Short View Summary
Etiology
Organism Stages
Oocyst
Tachyzoite
Tissue Cyst
Transmission and Epidemiology
Pathogenesis and Immunity
Genetic Susceptibility
Pathology
Lymph Node
Central Nervous System
Lung
Eye
Skeletal and Heart Muscle
Other Organ Systems
Clinical Manifestations
Toxoplasmosis in the Immunocompetent Patient
Toxoplasmosis in the Immunodeficient Patient
Toxoplasmosis in the Solid-Organ Transplant Patient
Heart Transplantation
Kidney Transplantation
Liver Transplantation
Toxoplasmosis in the Bone Marrow Transplant and Hematopoietic Stem Cell Transplant Recipient
Toxoplasmosis in the AIDS Patient
Ocular Toxoplasmosis in Immunocompetent Patients
Toxoplasmosis During Pregnancy
Congenital Toxoplasmosis
Diagnosis
Serologic Tests for Demonstration of Antibody
Immunoglobulin G Antibodies
Sabin-Feldman Dye Test
Indirect Fluorescent Antibody Test
Agglutination and AC/HS Tests
Immunoglobulin G Enzyme-Linked Immunosorbent Assay
Immunoglobulin G Avidity Test
Immunoglobulin M Antibodies
Immunoglobulin M Indirect Fluorescent Antibody Test
Immunoglobulin M Enzyme-Linked Immunosorbent Assay
Immunoglobulin M Immunosorbent Agglutination Assay
Immunoglobulin A Antibodies
Immunoglobulin E Antibodies
Polymerase Chain Reaction
Histologic Diagnosis
Isolation of Toxoplasma gondii
Radiologic Methods
Cerebrospinal Fluid Abnormalities
Diagnosis of Specific Clinical Entities
Toxoplasmosis in the Immunocompetent Patient
Toxoplasmosis in the Immunodeficient Patient
Ocular Toxoplasmosis
Toxoplasma gondii Infection in Pregnancy
Congenital Infection in the Fetus and Newborn
Therapy
Therapy Regimens in Specific Clinical Entities
Toxoplasmosis in the Immunocompetent Patient
Toxoplasmosis in the Immunodeficient Patient
Ocular Toxoplasmosis
Acute Acquired Toxoplasma Infection in Pregnant Women
Congenital Infection
Prevention and Prophylaxis
General Methods
Serologic Screening and Prophylaxis
Acute Toxoplasma gondii Infection and Toxoplasmosis in the Immunodeficient Patient
Congenital Toxoplasma gondii Infection and Toxoplasmosis
Acknowledgments
Key References
References
279 Giardia lamblia
Short View Summary
Description of the Pathogen
Some Unique Biologic Aspects
Epidemiology
Pathogenesis and Immune Response
Clinical Manifestations
Diagnosis
Therapy
Prevention
Key References
References
280 Trichomonas vaginalis
Short View Summary
Taxonomy
Epidemiology
Clinical Manifestations
Diagnosis
Therapy
Complications
Key References
References
281 Babesia Species
Short View Summary
Epidemiology
United States: Babesia microti
Geographic Distribution
Incidence and Prevalence
Modes of Transmission
Tick Bite
Blood Transfusion
Transplacental Passage
Solid Organ Transplantation
Risk Factors
United States: Other Babesia Species
Europe: Babesia divergens
Europe: Other Babesia Species
Asia: Babesia venatorum
Asia: Other Babesia Species
Rest of the World
Microbiology
The Enzootic Cycle of Babesia microti
Ticks and Reservoir Hosts
Parasite Acquisition by Ticks
Parasite Transmission to Hosts
Classification of Babesia Species
Single-Gene Analysis
Whole-Genome Analysis
Clinical Manifestations
Babesia microti Infection
Babesia duncani Infection
Babesia divergens Infection
Babesia venatorum Infection
Pathogenesis
Erythrocyte Clearance and Rupture
Inflammatory and Immune Response
Diagnosis
Routine Laboratory Findings
Microscopy
Nucleic Acid Amplification
Serology
Therapy
Asymptomatic Babesia microti Infection
Mild Babesia microti Infection
Severe Babesia microti Infection
First-Line Antimicrobial Therapy
Adjunctive Exchange Transfusion
Alternative Antimicrobial Regimens
Severely Immunocompromised Patients
Asplenic Patients
Infection With Other Babesia Species
Prevention
Acknowledgments
Key References
References
282 Cryptosporidiosis (Cryptosporidium Species)
Short View Summary
The Parasites
Epidemiology
Pathology and Pathogenesis
Host Response and Immunity
Clinical Manifestations
Immunocompetent Individuals in High-Income Countries
Childhood Diarrhea in Low- and Middle-Income Countries
Cryptosporidium and Malnutrition
Cryptosporidiosis in HIV Infection
Transplant Patients
Diagnosis
Management
Antiparasitic Drugs
Prevention
Key References
References
283 Cyclospora cayetanensis, Cystoisospora belli, Sarcocystis Species, Balantidium coli, and Blastocystis Species
Short View Summary
Coccidia Other Than Cryptosporidia
Cyclospora
Life Cycle
Epidemiology
Clinical Manifestations
Diagnosis
Therapy
Cystoisospora belli
Life Cycle
Epidemiology
Clinical Manifestations
Diagnosis
Therapy
Sarcocystis Species
Life Cycle
Epidemiology
Clinical Manifestations
Diagnosis
Therapy
Prevention
Balantidium coli
Life Cycle
Epidemiology
Clinical Manifestations
Diagnosis and Therapy
Blastocystis Species
Life Cycle
Epidemiology
Pathogenicity
Clinical Manifestations
Diagnosis
Therapy
Acknowledgment
Key References
References
I Diseases Due to Toxic Algae
284 Human Illness Associated With Harmful Algal Blooms
Short View Summary
Ciguatera Fish Poisoning
Paralytic Shellfish Poisoning
Neurotoxic Shellfish Poisoning
Diarrhetic Shellfish Poisoning
Amnesic Shellfish Poisoning
Azaspiracid Shellfish Poisoning
Cyanobacteria Exposure Syndromes, including Lyngbya
Pfiesteria-Associated Syndrome
References
J Diseases Due to Helminths
285 Introduction to Helminth Infections
Biology of Helminths
Epidemiology
Pathogenesis and Host-Parasite Relationship
Diagnosis of Helminth Infections
Treatment of Helminth Infections
Prevention and Control
Key References
References
286 Intestinal Nematodes (Roundworms)
Short View Summary
Intestinal Nematodes
Ascaris Lumbricoides
Epidemiology
Life Cycle
Clinical Syndromes
Diagnosis
Management
Enterobius Vermicularis
Epidemiology
Life Cycle
Clinical Syndromes
Diagnosis
Management
Hookworms
Epidemiology
Life Cycle
Clinical Syndromes
Diagnosis
Management
Strongyloides Stercoralis
Epidemiology
Life Cycle
Clinical Syndromes
Diagnosis
Management
Trichuris Trichiura
Epidemiology
Life Cycle
Clinical Syndromes
Diagnosis
Management
Key References
References
287 Tissue Nematodes, Including Trichinellosis, Dracunculiasis, Filariasis, Loiasis, and Onchocerciasis
Short View Summary
Trichinellosis
Life Cycle of Trichinella
Epidemiology
Pathogenesis and Pathology
Clinical Manifestations
Diagnosis
Therapy
Prevention
Haycocknema Perplexum Infection
Dracunculiasis
Life Cycle of the Parasite
Epidemiology
Clinical Manifestations
Diagnosis and Therapy
Control and Eradication
Filariases
Lymphatic Filariasis
Life Cycle of the Parasite
Epidemiology
Clinical Manifestations
Pathogenesis and Pathology
Diagnosis
Therapy
Prevention, Control, and Eradication
Tropical Pulmonary Eosinophilia
Loiasis
Life Cycle of the Parasite
Epidemiology
Clinical Manifestations
Diagnosis
Therapy
Prevention and Control
Onchocerciasis
Life Cycle of the Parasite
Epidemiology
Pathology and Clinical Manifestations
Diagnosis
Therapy
Prevention and Control
Mansonellosis
Zoonotic Filariae Reported to Cause Human Disease
References
288 Trematodes (Schistosomes and Liver, Intestinal, and Lung Flukes)
Short View Summary
Schistosomes
Life Cycle
Epidemiology
Pathogenesis
Clinical Syndromes
Schistosome Dermatitis (“Swimmer’s Itch”)
Acute Schistosomiasis (Katayama Fever)
Chronic Schistosomiasis
Intestinal and Hepatosplenic Schistosomiasis
Genitourinary Schistosomiasis
Pulmonary Hypertension and Glomerulopathy
Ectopic Egg Deposition and Central Nervous System Schistosomiasis
Coinfections
Diagnosis
Parasitologic Tests
Serologic Tests
Evaluation of Persons With Confirmed Schistosomiasis
Therapy
Praziquantel for Treatment of Schistosomiasis
Other Antischistosomal Drugs: Oxamniquine and Artemisinin Derivatives
Management of Acute Schistosomiasis
Evaluation of Therapy
New Medications for Schistosomiasis
Prevention and Control of Schistosomiasis
Liver Flukes
Clonorchiasis and Opisthorchiasis
Clinical Manifestations
Diagnosis and Therapy
Fascioliasis
Clinical Manifestations
Diagnosis
Therapy
Intestinal Flukes
Fasciolopsiasis
Heterophyiasis, Metagonimiasis, and Haplorchiasis
Echinostomiasis
Diagnosis and Therapy
Lung Flukes
Paragonimiasis
Clinical Manifestations
Diagnosis and Therapy
Prevention of Foodborne Fluke Infections
Key References
References
289 Tapeworms (Cestodes)
Short View Summary
Cestode Biology
Parasite Life Cycle
Disease Pathogenesis and Immunology
Intestinal Tapeworms
Diphyllobothrium latum
Hymenolepis nana
Taenia saginata
Taenia solium
Other Species Causing Tapeworm Infection in Humans
Diagnosis
Therapy
Niclosamide
Praziquantel
Invasive Cestode Infections
Cysticercosis
Clinical Presentation
Diagnosis
Treatment
Echinococcosis (Hydatid and Alveolar Cyst Disease)
Cystic Echinococcosis
Clinical Presentation
Diagnosis
Treatment
Alveolar Echinococcosis
Other Invasive Cestodes
Prevention
Key References
References
290 Visceral Larva Migrans and Other Uncommon Helminth Infections
Short View Summary
Visceral Larva Migrans (Toxocariasis)
Life Cycle in the Dog
Infection in Humans
Prevalence
Clinical Manifestations
Diagnosis
Differential Diagnosis
Treatment and Management
Prevention
Ocular Larva Migrans
Baylisascariasis
Anisakiasis
Life Cycle in Marine Mammals
Clinical Syndrome
Laboratory Findings
Diagnosis
Treatment
Prevention
Cutaneous Larva Migrans (Creeping Eruption)
Eosinophilic Meningitis
Gnathostomiasis
Life Cycle
Clinical Manifestations
Diagnosis
Differential Diagnosis
Treatment
Prevention
Abdominal Angiostrongyliasis
Eosinophilic Gastroenteritis
Dirofilariasis
Capillariasis
Swimmer’s Itch
Key References
References
K Ectoparasitic Diseases
291 Introduction to Ectoparasitic Diseases
Taxonomy of Ectoparasites
Epidemiology of Ectoparasitic Diseases
Mechanisms of Ectoparasite-Borne Diseases and Injuries
Conclusions
Key References
References
292 Lice (Pediculosis)
Short View Summary
Epidemiology
Diagnosis
Clinical Manifestations and Differential Diagnosis
Head Lice
Body Lice
Crab Lice (Pediculosis Pubis)
Therapy
Therapy for Pediculosis Capitis
Therapy for Body Lice
Prevention
Key References
References
293 Scabies
Short View Summary
Epidemiology
Transmission
Clinical Manifestations
Diagnosis
Therapy
Prevention
Conclusion
Key References
References
294 Myiasis and Tungiasis
Short View Summary
Myiasis
Epidemiology
Clinical Manifestations
Therapy
Prevention and Control
Flea Infestations
Tungiasis
Epidemiology
Clinical Manifestations
Therapy
Prevention and Control
Key References
References
295 Mites, Including Chiggers
Short View Summary
Mite Taxonomy and Ecology
Epidemiology and Outcomes of Mite Infestations
Diagnosis and Management of Mite Infections
Delusional Mite and Other Ectoparasitic Infestations
Prevention of Mite Infections and Mite-Transmitted Infectious Diseases
Conclusion
Key References
References
296 Ticks, Including Tick Paralysis
Short View Summary
Tick Biology, Behavior, and Taxonomy
Epidemiology of Tick-Borne Infectious Diseases
Tick-Borne Bacterial Infections
Spirochetal Infections (Borrelioses)
Lyme Borreliosis
Southern Tick-Associated Rash Illness (STARI)
Tick-Borne Relapsing Fevers
Spotted Fever Group Rickettsial Infections
Q (Query) Fever
Tularemia
Tick-Borne Ehrlichioses and Anaplasmosis
Tick-Borne Protozoal Infections
Babesial Infections
Tick-Borne Viral Infections
Tick-Borne Viral Encephalitides
New World TBEVs: Powassan Encephalitis
Old World TBEVs
Tick-Borne Hemorrhagic Fever Viruses
Tick-Borne Coltiviruses
Tick Paralysis
Red Meat Allergy After Tick Bites
Tick-Transmitted Coinfections
Prevention and Control of Tick-Borne Infectious Diseases and Paralytic Poisonings
Conclusions
Key References
References
L Diseases of Unknown Etiology
297 Kawasaki Disease
Short View Summary
Epidemiology
Etiology
Clinical Manifestations
Exanthem
Conjunctival Injection
Oropharyngeal Changes
Peripheral Extremity Changes
Cervical Lymphadenopathy
Associated Clinical Features
Arthritis
Gastrointestinal Features
Diagnosis
Differential Diagnosis
Pathology
Genetics
Therapy
Cardiovascular Involvement
Long-Term Outcome
Key References
References
IV Special Problems
A Nosocomial Infections
298 Infection Prevention and Control in the Health Care Setting
Short View Summary
Pathogen Transmission in the Hospital
Hand Hygiene
Disinfection and Sterilization (See Chapter 299)
Environmental Cleaning and Disinfection
Methods of Environmental Cleaning and Disinfection
Water Management
Transmission of Waterborne Pathogens
Biofilms in Hospital Plumbing
Legionnaires’ Disease
Disinfection of Hospital Water
Wastewater Plumbing Contamination
Air Handling
Air Handling for Airborne Infections
Air Handling to Prevent Nosocomial Mold Infections
Air Handling in the Operating Room
Air Quality
Transmission-Based Infection-Control Precautions
Colonization
Organisms Transmitted by Contact
Organisms Transmitted by Droplet
Organisms Transmitted by the Airborne Route
Organisms Transmitted by Aerosol
Device-Related Infections
Ventilator-Associated Pneumonia (See Chapter 301)
Measures to Prevent Ventilator-Associated Pneumonia
Selective Oral and Digestive Decontamination
Ventilator-Associated Events
“Bundled” Ventilator-Associated Pneumonia Prevention Strategies
Central Venous Catheter–Associated Infections (See Chapter 300)
Preventive Measures for Catheter Insertion
Preventive Measures for Catheter Maintenance
Chlorhexidine Gluconate Daily Baths
“Bundled” Catheter-Associated Bloodstream Infection–Prevention Strategies
Catheter-Associated Urinary Tract Infections (See Chapter 302)
Measures to Prevent Catheter-Associated Urinary Tract Infections
Surveillance
Active Microbial Surveillance
Decolonization and Skin Antisepsis
Management of Nosocomial Transmission of Multidrug-Resistant Organisms
Typing of Isolates
Surveillance and Public Health Reporting
Outbreak Investigation
Special Situation: Varicella-Zoster Virus Exposure Investigation
Management of Exposed Patients
Management of Exposed Personnel
Occupational Medicine
Preexposure Screening
Preexposure Immunizations
Influenza Immunization
Preventing Transmission of Respiratory Viruses to Patients
Universal and Standard Precautions
Postexposure Prophylaxis
Management of Occupational Exposure to Human Immunodeficiency Virus
Postexposure Testing and Follow-Up
Emerging Infectious Diseases
Key References
References
299 Disinfection, Sterilization, and Control of Hospital Waste
Definition of Terms
Rational Approach to Disinfection and Sterilization
Critical Items
Semicritical Items
Noncritical Items
Disinfection of Health Care Equipment and Surfaces
Chemical Disinfectants
Alcohol
Chlorine and Chlorine Compounds
Glutaraldehyde
Hydrogen Peroxide
Improved Hydrogen Peroxide
Iodophors
Ortho-phthalaldehyde
Peracetic Acid
Peracetic Acid With Hydrogen Peroxide
Phenolics
Quaternary Ammonium Compounds
Pasteurization
Ultraviolet Light
Sterilization
Steam Sterilization
Immediate-Use Steam Sterilization
Ethylene Oxide “Gas” Sterilization
Hydrogen Peroxide Gas Plasma
Vaporized Hydrogen Peroxide
Hydrogen Peroxide Plus Ozone
Current Issues in Sterilization
Inactivation of Creutzfeldt-Jakob Disease Agent
Disinfection
High-Level Disinfection of Semicritical Items
Current Issues With High-Level Disinfection of Semicritical Items
Reprocessing Endoscopes: A Shift From Disinfection to Sterilization
Inactivation of Human Papilloma Virus
Immersion Versus Perfusion of Channel Scopes Such as Cystoscopes
Ultrasound Probe Disinfection With Vaporized Hydrogen Peroxide
Low-Level Disinfection of Noncritical Environmental Surfaces and Patient Care Equipment
Adequacy of Room Cleaning and Disinfection With Chemical Germicides
Improving Room Cleaning and Disinfection, and Demonstrating the Effectiveness of Surface Decontamination in Reducing Health Care–Associated Infections
“No-Touch” Methods for Room Decontamination
Ultraviolet Light for Room Decontamination
Hydrogen Peroxide Systems for Room Decontamination
Comparison of Ultraviolet Irradiation Versus Hydrogen Peroxide for Room Decontamination
Continuous Room Decontamination
Surface Disinfection: Treatment Time (Wipes/Sprays) Versus Contact Time (Liquids)
OSHA Bloodborne Pathogen Standard
Emerging Pathogens, Antibiotic-Resistant Bacteria, and Bioterrorism Agents
Control of Hospital Waste
Conclusion
Acknowledgments
Key References
References
300 Infections Caused by Percutaneous Intravascular Devices
Short View Summary
Pathogenesis
Contamination of the Infusate
Contamination of the Catheter Hub and Lumen (Intraluminal Source)
Contamination of Skin at the Device Insertion Site (Extraluminal Source)
Epidemiology
CLABSI Rates
Patient-Related Issues
Catheter-Related Issues
Hospital-Related Issues
Microbiology
Diagnosis
Device-Specific Issues
Peripheral Intravenous Cannulization
Central Venous Catheters
Short-Term Issues
Parenteral Nutrition Issues
Long-Term Issues
Peripherally Inserted Central Venous Catheters
Care and Maintenance of Implanted Central Venous Catheters
Pulmonary Artery Catheters
Arterial Lines, Transducers, and Transducer Domes
Treatment of CLABSIs
Antimicrobial Lock Therapy
Prevention of Device-Associated Bacteremia
Before Insertion of Vascular Catheters
At Insertion
After Insertion
Special Approaches for the Prevention of CLABSIs
Antimicrobial Prophylaxis
Antimicrobial Lock Prophylaxis
Antimicrobial Catheters
Other Prevention Issues
Key References
References
301 Nosocomial Pneumonia
Short View Summary
Health Care–Associated Pneumonia
Epidemiology
Morbidity and Mortality
Pathophysiology
Risk Factors
Diagnosis
Clinical Pulmonary Infection Score
Summary and Recommendations for Clinical Diagnosis
Microbiologic Evaluation
Invasive Versus Noninvasive Respiratory Tract Sampling
Microbiology
Treatment
Empirical Therapy
Vancomycin Versus Linezolid for MRSA Coverage
Combination Versus Monotherapy for Gram-Negative Pathogens
Aerosolized Versus Intravenous Drug Delivery
Tailoring and Deescalating Therapy
Duration of Therapy
Prevention
Ventilator-Associated Pneumonia Prevention Bundles
Ventilator-Assisted Pneumonia as A Quality Metric
Key References
References
302 Health Care–Associated Urinary Tract Infections
Short View Summary
Definitions
Epidemiology
Incidence and Prevalence
CAUTI Risk Factors
Complications
Microbiology
Pathogenesis
Diagnosis
Significant Bacteriuria
Symptoms and Signs
Pyuria
Prevention
Prevention Strategies That Should Be Routine
Prevention Components of Infection Control Programs
Reduction of Unnecessary Catheterization
Alternatives to Indwelling Urethral Catheterization
Condom Catheterization
Intermittent Catheterization
Suprapubic Catheterization
Techniques for Catheter Insertion and Maintenance
Bundled CAUTI Prevention Programs
Prevention Strategies With Possible Benefit
Antiseptic- and Antimicrobial-Coated Catheters
Prophylaxis With Antimicrobial Agents
Systemic Antimicrobials
Methenamine Salts
Prevention Strategies With Little Benefit
Enhanced Meatal Care
Cranberry Products
Bladder Irrigation With Antimicrobial Therapy or Saline
Antimicrobial Drugs in the Drainage Bag
Routine Catheter Change
Prophylactic Antimicrobial Therapy at Catheter Removal or Replacement
Preclinical Strategies for CAUTI Prevention
Health Care–Associated Asymptomatic Bacteriuria
Routine Screening and Treatment
Prevention of Overtreatment of Asymptomatic Bacteriuria in Health Care Settings
Management of Health Care–Associated Urinary Tract Infection
Urine Culture and Catheter Replacement Before Treatment
Choice of Antimicrobial Agent
Duration
Nephrostomy Tubes and Ureteral Stents
Fungal Urinary Tract Infection
Summary
Key References
References
303 Health Care–Acquired Hepatitis
Short View Summary
Historical Background
Current Epidemiology of Health Care–Associated Hepatitis B and C Outbreaks in the United States
Fecal-Oral Transmission
Hepatitis A
Hepatitis E
Seroprevalence of Hepatitis E in Developed Countries and Risk of Bloodborne Transmission
Other Nosocomial Transmission
Hepatitis B
Epidemiology
Incidence After Exposure
Reported Transmissions
Worker-to-patient transmission.
Patient-to-worker transmission.
Dialysis setting.
Other nosocomial transmissions.
Vaccine Acceptance and Response Among Health Care Workers, and Duration of Immunity
Postexposure Management
Hepatitis C
Seroprevalence
Incidence After Occupational Exposure
Reported Transmissions
Worker-to-patient transmission.
Transmission in dialysis setting.
Solid tumor transplantation.
Other nosocomial transmissions.
Management
Hepatitis D
Key References
References
304 Transfusion- and Transplantation-Transmitted Infections
Short View Summary
Transfusion-Associated Infections
Scope of Blood Transfusion
Bloodborne Pathogens
Human Immunodeficiency Virus Type 1
Human Immunodeficiency Virus Type 2
Human T-Cell Lymphotropic Virus Types 1 and 2
Other Retroviruses
Hepatitis B and D Viruses
Hepatitis C Virus
Hepatitis A Virus
Hepatitis E Virus
West Nile Virus and Other Arboviruses
Herpesviruses
Parvovirus B19
Non–A-E Hepatitis
Bacterial Pathogens
Red Blood Cells
Platelets
Other Agents Transmitted Through Blood Components
Tick-borne Bacteria
Parasites
Prions
Infectious Diseases Transmitted Through Transplantation of Solid Organs and Other Tissues
Organ Transplant–Transmitted Bloodborne Pathogens
Pathogens Causing Encephalitis
Strongyloidiasis
Microsporidiosis
Ehrlichiosis
Key References
References
B Infections in Special Hosts
305 Infections in the Immunocompromised Host
Components of Host Defense
Cellular and Humoral Immunity
Innate Immunity
Granulocytes
Monocytes and Macrophages
Natural Killer Cells
Impact of Treatment on Cellular Immunity
Impact of Treatment on Humoral Immunity
Humoral Immunity and the Spleen
Platelets
The Integument as Host Defense
Skin
Respiratory Tract
Alimentary Tract and Normal Microbiota as Host Defense
Dysbiosis
Mucosal Barrier Injury
Nutritional Status
Comorbidity and Host Defense
Fever and the Inflammatory Response
Systemic Inflammatory Response Syndrome, Immune Reconstitution Inflammatory Syndrome, and Host-Directed Therapy (See Chapters 49 and 73)
Infections by Site
Bacteremia
Bacteremia Related to Intravascular Catheters
Bacteremia From the Gastrointestinal Tract
Oral Cavity Infections
Respiratory Tract Infections
Skin Infections
Gastrointestinal Tract Infections
Urinary Tract Infections
Central Nervous System Infections
Liver Infections
Sequence of Infections
Role of Molecular Diagnostics in Infections in the Immunocompromised Host
Conclusion
Key References
References
306 Prophylaxis and Empirical Therapy of Infection in Cancer Patients
Short View Summary
Epidemiology and Risk Factors for Infections in Cancer Patients
Neutropenia
Mucositis and Microbiota Alterations
Central Venous Catheters
Genetic Factors
New Therapies
Biologic Agents and Other New Drugs
Chimeric Antigen Receptor T-Lymphocyte Therapy
Surgery
Etiology
Bacterial Infections
Fungal Infections
Viral Infections
Other Pathogens
Prevention of Infections in Cancer Patients
Prevention of Bacterial Infections
Antibacterial Chemoprophylaxis
Decolonization for Prevention of Infections Due to Resistant Bacteria, Including Fecal Microbiota Transplantation
Prophylaxis of Tuberculosis
Prevention of CVC-Related Infections (See Chapter 300)
Prevention of Fungal Infections
Primary Antifungal Chemoprophylaxis
Secondary Antifungal Prophylaxis
Prophylaxis Against Pneumocystis jirovecii
Prevention of Viral Infections
Other Prophylactic Measures
Role of Colony-Stimulating Factors in Prophylaxis
Role of Immunoglobulins in Prophylaxis
Infection Control: Isolation and Antimicrobial Stewardship
Food and Lifestyle
Vaccination
Treatment of Complications in Neutropenic Cancer Patients
Empirical Antibacterial Therapy of Fever During Neutropenia
Patients at Low Risk
Patients at High Risk
Duration of Antibacterial Treatment
Empirical and Preemptive (Diagnostic-Oriented) Antifungal Therapy
Management of a Neutropenic Patient With a Localized Infection
Catheter-Related Infection
Pneumonia
Abdominal Infections
Other Treatments
Granulocyte Transfusions
Colony-Stimulating Factors
Conclusions
Key References
References
307 Infections in Recipients of Hematopoietic Stem Cell Transplants
Short View Summary
Basic Transplantation Techniques
Chemotherapy
Irradiation
Reduced-Intensity Conditioning or Nonmyeloablative Transplantation
Human Leukocyte Antigen Matching
Prevention of Infection
Clinical Syndromes Unique to the Hematopoietic Stem Cell Recipient
Hemorrhagic Cystitis (HC)
Venoocclusive Disease (Sinusoidal Obstruction Syndrome)
Graft-Versus-Host Disease
Hepatitis
Pneumonia Syndromes
Diarrhea
Rash
Osteomyelitis
Patterns of Immunosuppression at Different Times After Myeloablative HSCT
Preengraftment Risk Period
Postengraftment Risk Period
Late Risk Period
Immunodeficiency After Nonmyeloablative HSCT
Measures to Reduce Risks for Infection
Natural History of Individual Infections After HSCT
Bacterial Infections
Encapsulated Bacteria
Viridans-Group Streptococci
Clostridioides difficile
Mycobacteria
Intracellular Bacteria
Viral Infections
Herpes Simplex Virus
Cytomegalovirus
Varicella-Zoster Virus
Adenovirus
Norovirus
Respiratory Viruses
Epstein-Barr Virus
Human Herpesvirus 6
Parvovirus
Fungal Infections
Pneumocystis
Candida
Aspergillus
Other Yeasts
Other Molds
Parasitic Infections
Methods of Immune System Reconstitution After HSCT
Vaccination
Immunoglobulin Replacement
Key References
References
308 Infections in Solid-Organ Transplant Recipients
Fundamentals of Immunosuppressive Therapy
Corticosteroids
Antimetabolite Agents
Calcineurin Inhibitor Agents
Mammalian Target of Rapamycin Inhibitors
Biologic Agents
Pretransplant Evaluation for Infections
Transplant Candidates Colonized With Multidrug-Resistant Bacteria
Selective Testing for Specific Infections in Transplant Candidates
Time of Occurrence of Infections After Transplantation
Infections in First 30 Days
Infections Between 30 to 180 Days
Infections Occurring 6 Months or Later
Unique Characteristics of Infections in Different Types of Transplants
Kidney Transplant Recipients
Heart Transplant Recipients
Lung and Heart-Lung Transplant Recipients
Invasive Aspergillosis After Lung Transplantation
Liver Transplant Recipients
Abdominal Infections After Liver Transplantation
Fungal Infections After Liver Transplantation
Pancreas Transplant Recipients
Small Bowel Transplant Recipients
Specific Sites and Types of Infection
Infections of the Skin and Surgical Site
Infections of the Urinary Tract
Infections of the Bloodstream
Pulmonary Infections
Tuberculosis
Diagnostic Considerations
Management of Tuberculosis
Treatment of Latent Tuberculosis
Treatment of Active Tuberculosis
Pulmonary Infections Due to Endemic Mycoses
Coccidioidomycosis
Histoplasmosis
Abdominal and Gastrointestinal Infections
Diarrhea
Central Nervous System Infections
Specific Problems of Viral Infections
Cytomegalovirus
Risk Factors
Clinical Manifestations
Laboratory Diagnosis and Immune Monitoring
Prevention
Treatment
Epstein-Barr Virus and Posttransplantation Lymphoproliferative Disorder
Immunobiology
Risk Factors
Clinical Manifestations and Diagnosis
Prevention and Treatment
Herpes Simplex Virus
Varicella-Zoster Virus
Human Herpesviruses 6 and 7
Human Herpesvirus 8 (Kaposi Sarcoma Herpesvirus)
Human Immunodeficiency Virus
Human Immunodeficiency Virus Screening
Human Immunodeficiency Virus–to–Human Immunodeficiency Virus Transplantation
RNA Respiratory Viruses
Polyomaviruses
Adenovirus
Parvovirus B19
Zika Virus
Norovirus
Hepatitis Viruses
Hepatitis A Virus
Hepatitis B Virus
Liver Transplant Candidates and Recipients
Nonliver Organ Transplant Candidates and Recipients
Hepatitis C Virus
Hepatitis E Virus
Donor-Transmitted Infections (See Chapter 304)
Donor-Derived Bacterial Infections
Donor-Derived Fungal Infections
Other Pathogens With Potential for Transmission With the Allograft
Approach to Fever in the Transplant Recipient
Fever Without an Evident Source
Vaccination in Organ Transplant Candidates and Recipients
Selected Specific Vaccines
Influenza
Pneumococcus
Herpes Zoster
Hepatitis B
Hepatitis C
Acknowledgment
Key References
References
309 Infections in Patients With Spinal Cord Injury
Short View Summary
Factors That Predispose to Infection
Challenges in Evaluating Patients for Infection
Urinary Tract Infection
Pneumonia
Infection of Pressure Sores
Osteomyelitis
Bloodstream Infection
Intraabdominal Infection
Multiresistant Organisms in the Spinal Cord Injury Setting
Clostridioides difficile (Formerly Clostridium difficile)
References
310 Infections in Older Adults
Short View Summary
Predisposition of Older Adults to Infection
Comorbid Illness
Waning Immunity With Age (Immune Senescence)
Nutrition
Social and Environmental Factors
Presentation of Infection in Seniors
Antibiotic Management in Seniors
Antimicrobial Treatment
Antibiotic Stewardship
Antibiotics at the End of Life
Age-Related Differences in Specific Clinical Syndromes
Pneumonia
Urinary Tract Infection
Bacteremia and Sepsis
Infective Endocarditis
Prosthetic Device Infections
Gastrointestinal Infections
Tuberculosis
Human Immunodeficiency Virus
Fever of Unknown Origin
Immunization of Older Adults
Pneumococcal Vaccine
Influenza
Zoster
Other Vaccines
Travel Recommendations for Older Adults
Key References
References
311 Infections in Asplenic Patients
Short View Summary
Anatomy of the Spleen
Function of the Spleen
Regulation of Inflammation
Filtration and Clearance
Adaptive Immunity
Innate Immunity
Hematopoiesis/Hemostasis
Types of Asplenia
Congenital Asplenia
Acquired Asplenia
Acquired Hyposplenia
Assessment for Splenic Function
Epidemiology and Risk Factors of Sepsis in Asplenic Patients
Clinical Presentation of Sepsis Secondary to Asplenia
Microbial Agents Causing Postsplenectomy Sepsis
Bacteria
Protozoa
Diagnosis of Postsplenectomy Sepsis
Management of Postsplenectomy Sepsis
Prevention of Postsplenectomy Sepsis
Prophylactic Antibiotics
Vaccines
Patient Education
Key References
References
312 Infections in Injection Drug Users
Short View Summary
Host Defenses
Immune Changes
Skin and Soft Tissue Infections
Infection Sites
Abscess
Microbiology of Abscesses
Diagnosis of Abscess
Management of Soft Tissue Infections
Skin Ulcers
Necrotizing Fasciitis
Pyomyositis
Injection Anthrax
Bone and Joint Infections
Epidemiology of Skeletal Infections
Site of Skeletal Infection
Diagnosis and Management of Skeletal Infections
Bacteremia and Infective Endocarditis
Epidemiology
Microbiology
Pathophysiology
Clinical Manifestations
Diagnosis
Therapy
Prognosis
Noncardiac Vascular Infections
Septic Thrombophlebitis
Mycotic Aneurysm
Pulmonary Infections
Pathophysiology
Clinical Patterns
Tuberculosis in Injection Drug Users
Hepatitis
Risk Factors
Hepatitis B
Delta Virus
Hepatitis C
Hepatitis A
Hepatitis E
Splenic Abscess
Clinical Manifestations
Therapy
Central Nervous System Infections
Risk Factors
Cerebral Mycotic Aneurysm
Brain Abscess and Subdural Empyema
Meningitis
Spinal Epidural Abscess
Tetanus and Wound Botulism
Ocular Infections
Endophthalmitis
Human Immunodeficiency Virus Infection
Epidemiology
Prevention
Therapy and Prognosis
Sexually Transmitted Diseases
Epidemiology
Syphilis
Key References
References
313 Surgical Site Infections and Antimicrobial Prophylaxis
Short View Summary
Historical Background
Principles of Surgical Site Infection Prevention
Determinants and Pathophysiology
Species and Sources of Wound Bacteria
Virulence Factors of Major Wound Pathogens
Clean Wound Infections
Contaminated Wound Infections
Wound Microenvironment and Operative Effects on Immunity
Foreign Material and Operative Trauma to Tissue
Effect of Operative Procedures on Systemic and Local Immunity
Risk Factors for Surgical Site Infections
Patient Factors
Procedural and Proceduralist Factors
Postoperative Factors
Prevention of Surgical Site Infections
General Concepts
Perioperative Antimicrobial Prophylaxis
Antimicrobial Prophylaxis: Drug Selection and Dosing
Basic Principles
Drug Selection With Rising Incidence of Antibiotic-Resistant Pathogens (e.g., MRSA)
Methicillin-Resistant S. aureus–Specific Prophylaxis
Special Considerations With Prophylaxis in Colorectal Surgery
Dosing in Obese Patients
Antimicrobial Prophylaxis: Timing of Administration and Redosing
Initial Dose Timing
Intraoperative Redosing
Antimicrobial Prophylaxis: Duration
Novel Methods of Antimicrobial Prophylaxis: Local and Topical Compounds
Adverse Effects of Prophylaxis
Cost-Benefit of Prophylaxis
Use of Surgical Prophylaxis Compliance as a Reported Measure of Health Care Quality
Surgical Site Infection Surveillance
Postdischarge Surgical Site Infection Surveillance
Key References
References
C Surgical- and Trauma-Related Infections
314 Burns
Short View Summary
Burn Injury
Types of Injuries Admitted to Burn Centers
Epidemiology
Survival in Burn Injury
Infectious Complications of Burn Injury
Microbiology
Pathogenesis and Microbial Evolution of Burn Wound Colonization and Infection
Fungal Colonization and Infection Following Burn Injury
Viral Infections Following Burn Injury
Diagnosis
Defining Infection in Burn Patients
Sepsis and Bloodstream Infections
Pneumonia
Wound Infections
Treatment
Empirical Therapy of Infections
Dosing of Antimicrobials in Burns
Antifungal Therapy
Surgical Management and Topical Therapy
Prevention
Infection Prevention and Health Care–Associated Infections
Antimicrobial Stewardship in the Burn Unit
Other Strategies to Modify Infection Risk
Conclusions
Key References
References
315 Bites
Short View Summary
Animal Bites
Management of Animal Bites
Venomous Snakebites
Lip Wounds and Paronychia
Human Bites
Management of Human Bites
Clenched-Fist Injuries
Key References
References
D Immunization
316 Immunization
Immunologic Basis of Vaccination
Determinants of Immunogenicity
Live Versus Killed or Subunit Vaccines
Dose
Adjuvants
Route of Administration
Age
Components of the Immune Response
Mobilization of the Adaptive Immune Response
Unanticipated Responses
Temporal Course of the Immune Response
Measurement of the Immune Response
Vaccine Development
General Principles of Immunization
Currently Available Immunizing Agents
Vaccines
Adenovirus Vaccine
Anthrax Vaccine
Bacillus Calmette-Guérin Vaccine
Cholera Vaccine
Diphtheria Toxoid
Haemophilus influenzae Type b Vaccine (Hib)
Hepatitis A Vaccine
Hepatitis B Vaccine
Human Papillomavirus Vaccines
Influenza Virus Hemagglutinin Vaccines–Inactivated and Recombinant (IIV and RIV)
Live-Attenuated Influenza Vaccine
Japanese Encephalitis
Measles-Containing Vaccine
Meningococcal Vaccines
Mumps Vaccine
Pertussis-Containing Vaccine
Plague Vaccine
Pneumococcal Polysaccharide Vaccine
Pneumococcal Conjugate Vaccine
Polio Vaccine
Rabies Vaccine
Rotavirus Vaccines
Rubella Vaccine
Smallpox Vaccine
Tetanus Toxoid
Typhoid Vaccine
Varicella Vaccine
Yellow Fever Vaccine
Zoster Vaccine
Immunoglobulin Preparations
Intramuscular Immune Globulin
Indications for Use of Intramuscular Immune Globulin
Replacement therapy for antibody deficiency disorders.
Hepatitis A prophylaxis.
Measles prophylaxis.
Specific Intramuscular Immune Globulin Preparations
Hepatitis B immune globulin.
Rabies immune globulin.
Tetanus immune globulin.
Varicella-zoster immune globulin.
Immune Globulin Intravenous
Indications for Use of Immune Globulin Intravenous
Specific Immune Globulins for Intravenous Use
Vaccinia Immune Globulin
Respiratory Syncytial Virus Immune Globulin and Palivizumab
Adverse Reactions to Immune Globulin Preparations
Immune Globulin Subcutaneous
Rh Immune Globulin
Use of Vaccines
Routine
Children
Adolescents
Adults
Special Circumstances
Travel
Occupational Exposure
Pregnancy
Immunocompromised States
Human Immunodeficiency Virus
Postexposure Immunization
Other Considerations
Storage and Handling of Vaccines
Assessing the Need for Immunization
Immunization Records
Parent and Patient Education
Simultaneous Administration and Intervals Between Immunizations
Combination Vaccines
Interrupted Schedules
Reporting of Disease and Adverse Events
Compensation for Vaccine Injuries
Standards for Immunization Practices
Methods to Improve Immunization Coverage
Sources of Information
Key References
References
E Zoonoses
317 Zoonoses
Short View Summary
One Health Initiative
Mechanisms of Transmission
Factors in the Emergence of Zoonotic Diseases
Prediction and Early Detection of Emerging and Reemerging Zoonotic Diseases
Zoonotic Diseases
Infections Associated With Wildlife
Bats
Rodents
Diseases Associated With Agricultural and Other Domestic Animals
Conclusions
References
F Protection of Travelers
318 Protection of Travelers
Short View Summary
Epidemiology of Travel-Related Illness
Immunization
Update of Routine Immunizations
Tetanus-Diphtheria–Acellular Pertussis
Measles-Mumps-Rubella
Influenza and Pneumococcal Vaccine
Varicella
Vaccines to Consider for All Destinations in the Developing World
Hepatitis A
Hepatitis B
Combination Hepatitis A and Hepatitis B Vaccine
Typhoid
Vaccines to Consider Only for Certain Destinations
Yellow Fever
Risk of Yellow Fever
Yellow Fever Entry Requirements
Yellow Fever Booster Doses
Meningococcal Disease
Rabies
Japanese Encephalitis
Polio
Cholera
Tick-Borne Encephalitis
Spacing and Interactions of Travel-Related Vaccines
Malaria Chemoprophylaxis
Epidemiology of Malaria in Travelers
Risk of Travelers’ Malaria
Choice of Malaria Chemoprophylactic Drugs
Adverse Effects of Antimalarial Drugs
Prevention of Plasmodium vivax and Plasmodium ovale Relapses
Standby Therapy Instead of Continuous Prophylaxis
Dengue
Chikungunya and Zika Virus
Traveler’s Diarrhea
Risk and Etiology
Prevention
Self-Treatment
Key Preventive Behaviors
Personal Protection Against Arthropods
Protection Against Foodborne Disease
Sex
Protection Against Bloodborne Disease
Protection Against Skin Diseases
Protection Against Pathogens Encountered by Swimming and Water Exposure
Prevention of Tuberculosis
Noninfectious Travel Problems
Medical Kit and Medical Care Abroad
Air Travel–Related Morbidity
Deep Venous Thrombosis/ Pulmonary Embolism
Jet Lag, Motion Sickness, and In-Flight Medical Emergencies
Altitude
Traveling Adults With Special Needs
Immunocompromised Travelers and Human Immunodeficiency Virus–Infected Travelers
Pregnant Travelers
Key References
References
319 Infections in Returning Travelers
Short View Summary
Fever
Epidemiology
History
Detailed Travel Itinerary
Chronology of Travel and Illness
Exposures
Immunization History
Antimalarial Prophylaxis or Treatment
Other Medications Ingested
Physical Examination
Considerations for the Common Travel-Related Febrile Illnesses
Malaria
Dengue
Chikungunya Fever
Zika Virus
Typhoid and Paratyphoid Fever
Viral Hepatitis
Rickettsial Disease
Leptospirosis
Respiratory Illness
Special Consideration of Ebola Virus Disease in Returning Travelers
Yellow Fever in Returning Travelers
Initial Office Approach to the Febrile Patient
Diarrhea in Travelers
Acute Traveler’s Diarrhea
Persistent Diarrhea in the Traveler
Skin Problems
Eosinophilia
Screening for Asymptomatic Infection
Key References
References