This is a timely and essential companion to the recently published Antimicrobial Resistance in the 21st Century, Second Edition. Antimicrobial resistance is a major threat to global population health, with government reports projecting it could result in over 10 million deaths in the next 35 years. Development of new agents to combat this threat is one of the WHO's top priorities, but in 2017, it conceded that the current drug development pipeline was insufficient to mitigate the threat. This book discusses recent progress and bolster new agent discovery and development, by providing researchers and students who will soon enter the field with a thorough guide to the advancements made in the last decade.
Coverage includes new systemic antimicrobials approved since 2010, with detailed analysis of antibiotics, antivirals, antifungals, and antiparasitics, as well as agents in development for future use. Discussion of each drug will include its chemical nature, pharmacology/pharmacokinetics, antimicrobial spectrum, dosage, adverse reactions, drug interactions, microbial resistance, indications, clinical efficacy compared to older agents, and lists of similar agents with cost comparison. This volume is designed for researchers and students of infectious disease and medical microbiology, as well as clinicians in need of a comprehensive guide to newly developed agents.
Author(s): I.W. Fong
Series: Emerging Infectious Diseases of the 21st Century
Publisher: Springer
Year: 2023
Language: English
Pages: 246
City: Cham
Preface
Contents
Chapter 1: Antimicrobial Resistance: A Crisis in the Making
1.1 Introduction
1.2 Antimicrobial Resistance: An Evolutionary Process
1.3 Mechanisms of Microbial Resistance
1.4 Bacterial Resistance
1.4.1 Restriction of Access
1.4.2 Modification of Target
1.4.3 Degradation by Enzymes
1.4.3.1 Beta-lactamases
1.4.3.2 Aminoglycoside-Modifying Enzymes
1.4.3.3 Chloramphenicol Acetyltransferase
1.4.3.4 Efflux Pumps
1.4.4 Genetic Mechanisms of Bacterial Resistance
1.5 The Toll of Antimicrobial Resistance
1.5.1 Effect on Healthcare
1.5.2 Economic Effect
1.6 Global Response to Antimicrobial Resistance
1.6.1 Comments on Global Response
References
Part I: New Antibacterial Agents
Chapter 2: New Cephalosporins: Fifth and Sixth Generations
2.1 Introduction
2.2 Ceftaroline
2.2.1 Mechanism of Action and Microbial Spectrum
2.2.2 Pharmacokinetics of Ceftaroline
2.2.3 Clinical Efficacy of Ceftaroline
2.2.4 Side Effects of Ceftaroline
2.3 Ceftobiprole
2.3.1 Mechanism of Action and Microbial Activity of Ceftobiprole
2.3.2 Pharmacology of Ceftobiprole
2.3.3 Phase 3 Clinical Studies of Ceftobiprole
2.3.4 Safety Profile of Ceftobiprole
2.3.5 Role of Ceftaroline and Ceftobiprole in Clinical Practice
2.4 Cefiderocol: A Novel Siderophore Cephalosporin
2.4.1 Chemistry and Mechanisms of Action of Cefiderocol
2.4.2 In Vitro Activity of Cefiderocol
2.4.3 Resistance to Cefiderocol
2.4.4 Pharmacokinetic/Pharmacodynamic Aspects of Cefiderocol
2.4.5 Efficacy and Tolerability of Cefiderocol
2.4.6 Role of Cefiderocol in Clinical Infectious Diseases
References
Chapter 3: New β-Lactam-β-Lactamase Inhibitor Combinations
3.1 Introduction
3.2 Ceftolozane-Tazobactam
3.2.1 Antimicrobial Activity of Ceftolozane/Tazobactam
3.2.2 Pharmacokinetics/Pharmacodynamics of Ceftolozane/Tazobactam
3.2.3 Resistance to Ceftolozane/Tazobactam
3.2.4 Clinical Efficacy and Safety of Ceftolozane/Tazobactam
3.2.5 Summary and Place in Therapy of Ceftolozane/Tazobactam
3.3 Ceftazidime/Avibactam
3.3.1 In Vitro Activity of Ceftazidime/Avibactam
3.3.2 Pharmacokinetic/Pharmacodynamics of Ceftazidime/Avibactam
3.3.3 Therapeutic Efficacy of Ceftazidime/Avibactam
3.3.4 Safety of Ceftazidime/Avibactam
3.3.5 Role of Ceftazidime/Avibactam in Gram-Negative Bacteria Infections
3.4 Carbapenem/β-Lactamase Inhibitor Combinations
3.4.1 Meropenem/Vaborbactam
3.4.2 Antibacterial Activity of Meropenem/Vaborbactam
3.4.3 Resistance to Meropenem/Vaborbactam
3.4.4 Pharmacologic/Pharmacodynamic Aspects of Meropenem/Vaborbactam
3.4.5 Clinical Efficacy of Meropenem/Vaborbactam
3.4.6 Imipenem-Cilastatin/Relebactam
3.4.7 In Vitro Activity of Imipenem/Relebactam
3.4.8 Pharmacokinetics/Pharmacodynamics of Imipenem/Relebactam
3.4.9 Clinical Efficacy and Side Effects of Imipenem/Relebactam
3.4.10 Place in Therapy of Meropenem/Vaborbactam and Imipenem/Relebactam
References
Chapter 4: New Glycopeptides: Telavancin, Dalbavancin, and Oritavancin
4.1 Introduction
4.2 Mechanism of Action and Resistance Mechanism
4.3 Second-Generation Glycopeptides
4.3.1 Telavancin
4.3.2 Pharmacology/Pharmacokinetics of Telavancin
4.3.3 In Vitro Activity of Telavancin
4.3.4 Clinical Efficacy and Side Effects of Telavancin
4.3.5 Dalbavancin
4.3.6 Pharmacokinetics and Pharmacodynamics of Dalbavancin
4.3.7 In Vitro Activity of Dalbavancin
4.3.8 Clinical Efficacy and Safety of Dalbavancin
4.3.9 Off-Label Use of Dalbavancin
4.3.10 Oritavancin
4.3.11 Pharmacokinetics and Pharmacodynamics of Oritavancin
4.3.12 In Vitro Activity of Oritavancin
4.3.13 Clinical Efficacy of Oritavancin
4.3.14 Off-Label Use of Oritavancin
4.3.15 Comments
References
Chapter 5: A New Fluoroquinolone: Delafloxacin
5.1 Introduction
5.2 Pharmacology and Pharmacokinetics
5.3 Pharmacodynamics
5.4 In Vitro Activity
5.4.1 Microbial Resistance
5.5 Clinical Efficacy
5.6 Adverse Events
5.7 Role in Therapy
References
Chapter 6: New Oxazolidinone: Tedizolid
6.1 Introduction
6.2 Antimicrobial Activity
6.3 Mechanisms of Resistance
6.4 Pharmacology and Pharmacokinetics
6.5 Clinical Activity
6.5.1 Safety
6.6 Place in Therapy
References
Chapter 7: New Tetracyclines: Eravacycline and Omadacycline
7.1 Introduction
7.2 Eravacycline
7.3 Pharmacokinetics and Pharmacodynamics of Eravacycline
7.4 Microbial Activity of Eravacycline
7.5 Resistance Mechanisms Affecting Eravacycline
7.6 Clinical Efficacy and Safety of Eravacycline
7.7 Omadacycline
7.7.1 Pharmacokinetics and Pharmacodynamics of Omadacycline
7.8 Microbiologic Activity of Omadacycline
7.8.1 Resistance to Omadacycline
7.9 Clinical Efficacy and Safety of Omadacycline
7.10 Place in Therapy with the Modern Tetracyclines
References
Chapter 8: Pleuromutilin: A New Class of Antibiotic: Lefamulin
8.1 Introduction
8.2 Chemical Structure and Mechanism of Action
8.3 Antimicrobial Activity
8.4 Microbial Resistance to Lefamulin
8.5 Pharmacokinetics
8.6 Clinical Efficacy
8.7 Adverse Effects
8.8 Place in Therapy
References
Chapter 9: New Anti-tuberculous Drugs: Bedaquiline, Delamanid, and Pretomanid
9.1 Introduction
9.2 Bedaquiline
9.2.1 Microbial Activity of Bedaquiline
9.2.2 Resistance to Bedaquiline
9.3 Pharmacokinetics of Bedaquiline
9.3.1 Drug-Drug Interactions of Bedaquiline
9.3.2 Adverse Effects of Bedaquiline
9.3.3 Efficacy of Bedaquiline
9.4 Delamanid
9.4.1 In Vitro Activity of Delamanid
9.4.2 Resistance to Delamanid
9.4.3 Pharmacokinetics of Delamanid
9.4.4 Efficacy and Safety of Delamanid
9.5 Pretomanid
9.5.1 In Vitro Activity of Pretomanid
9.5.2 Resistance to Pretomanid
9.5.3 Pharmacology of Pretomanid
9.5.4 Clinical Efficacy and Safety of Pretomanid
9.6 Conclusion and Discussion
References
Part II: New Systemic Antifungal Agents
Chapter 10: New Systemic Antifungal: Isavuconazole
10.1 Introduction
10.2 Isavuconazole
10.3 In Vitro Activity
10.4 Resistance to Isavuconazole
10.5 Pharmacology
10.6 Drug-Drug Interactions
10.7 Clinical Efficacy
10.7.1 Aspergillosis
10.7.2 Mucormycosis
10.7.3 Candidiasis
10.7.4 Other Fungal Infections
10.8 Safety
10.9 Conclusion
References
Part III: Anti-Parasitic Agents
Chapter 11: Newly Approved Anti-parasitic Drugs for Malaria, Fascioliasis, Onchocerciasis, Chagas Disease, and African Trypanosomiasis
11.1 Introduction
11.2 Benznidazole
11.2.1 Chagas Disease
11.2.2 Treatment of Chagas Disease
11.2.3 Efficacy of Benznidazole
11.2.4 Adverse Effects of Benznidazole
11.3 Fexinidazole
11.3.1 African Trypanosomiasis
11.3.2 Treatment of African Trypanosomiasis
11.3.3 Pharmacology of Fexinidazole
11.3.4 Clinical Efficacy of Fexinidazole
11.3.5 Side Effects of Fexinidazole
11.4 Moxidectin
11.4.1 Onchocerciasis
11.4.2 Treatment of Onchocerciasis
11.4.3 Pharmacology of Moxidectin
11.4.4 Mechanism of Action of Moxidectin
11.4.5 Clinical Efficacy of Moxidectin
11.4.6 Adverse Effects of Moxidectin
11.5 Tafenoquine
11.5.1 Plasmodium vivax Malaria
11.5.2 Pharmacology of Tafenoquine
11.5.3 Antimalarial Activity of Tafenoquine
11.5.4 Clinical Efficacy of Tafenoquine
11.5.5 Safety of Tafenoquine
11.6 Triclabendazole
11.6.1 Human Fascioliasis
11.6.2 Triclabendazole for Fascioliasis
11.6.3 Pharmacology of Triclabendazole
11.6.4 Clinical Efficacy of Triclabendazole
11.6.5 Treatment Failure and Resistance to Triclabendazole
11.6.6 Safety of Triclabendazole
11.7 Conclusion
References
Part IV: New Antiviral Agents
Chapter 12: New Antiretroviral Agents for HIV Infection
12.1 Introduction
12.2 Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)
12.2.1 Pharmacokinetics of Biktarvy (BIC/FTC/TAF)
12.2.2 Drug Interactions with Biktarvy (BIC/FTC/TAF)
12.2.3 Clinical Efficacy of Biktarvy (BIC/FTC/TAF)
12.2.4 Safety of Biktarvy (BIC/FTC/TAF)
12.2.5 Biktarvy Place in Management of HIV-1
12.3 Dovato (Dolutegravir/Lamivudine)
12.4 Pharmacokinetics of Dolutegravir/Lamivudine (Dovato)
12.5 Drug-Drug Interaction of Dovato (DTG/3TC)
12.6 Clinical Efficacy of Dovato (DTG/3TC)
12.6.1 Safety Issues of Dovato (DTG/3TC)
12.7 Conclusions on Dovato
12.8 Delstrigo (Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate)
12.8.1 Pharmacokinetics of Doravirine/Lamivudine/Tenofovir DF
12.8.2 Clinical Efficacy and Safety of Delstrigo (DOR/3TC/TDF)
12.8.3 Conclusion on Delstrigo (DOR/3TC/TDF)
12.9 Cabotegravir and Cabenuva (Cabotegravir/Rilpivirine)
12.9.1 Pharmacokinetics of Cabotegravir/Rilpivirine
12.9.2 Clinical Efficacy of Cabenuva (CAB-LA/RPV-LA)
12.9.3 Safety and Drug Interactions of Cabenuva (CAB/RPV)
12.9.4 Indication and Dosing of Cabenuva (CAB/RPV)
12.9.5 Cabotegravir for Prevention of HIV
12.9.6 Conclusion on Cabotegravir and Cabenuva
12.10 Ibalizumab-uiyk (Trogarzo)
12.10.1 Pharmacodynamics and Antiviral Activity of Ibalizumab
12.10.2 Resistance to Ibalizumab
12.10.3 Pharmacokinetics of Ibalizumab
12.10.4 Efficacy of Ibalizumab
12.10.5 Safety of Ibalizumab
12.10.6 Conclusion on Ibalizumab
12.11 Fostemsavir
12.11.1 Pharmacokinetics of Fostemsavir
12.11.2 Clinical Data on Fostemsavir
12.11.3 Safety of Fostemsavir
12.11.4 Conclusion on Fostemsavir
References
Chapter 13: New Antiviral Agents for Cytomegalovirus Diseases
13.1 Introduction
13.2 Letermovir
13.2.1 Pharmacokinetics of Letermovir
13.2.2 Drug Interactions of Letermovir
13.2.3 Clinical Efficacy of Letermovir
13.2.4 Safety of Letermovir
13.2.5 Letermovir Resistance
13.2.6 Conclusion on Letermovir
13.2.7 Maribavir for the Treatment of Cytomegalovirus Infection
13.2.8 Pharmacokinetics of Maribavir
13.2.9 Clinical Efficacy of Maribavir
13.2.9.1 Prophylactic Trials
13.2.9.2 Preemptive Trials
13.2.9.3 Maribavir for Resistant or Refractory CMV Infections
13.2.9.4 Safety of Maribavir
13.2.10 Resistance to Maribavir
13.2.11 Conclusion on Maribavir
References
Chapter 14: New Antiviral Agent for Influenza: Baloxavir
14.1 Introduction
14.2 Established Antivirals for Influenza Therapy
14.3 Baloxavir a Novel Anti-Influenza Agent
14.4 Pharmacokinetics of Baloxavir
14.5 Drug-Drug Interactions of Baloxavir
14.6 Clinical Efficacy of Baloxavir
14.7 Viral Resistance to Baloxavir
14.8 Role of Baloxavir in Influenza Treatment
References
Chapter 15: Direct Antiviral Agents for Hepatitis C
15.1 Introduction
15.2 Treatment of Hepatitis C
15.3 Combinations of Direct Antiviral Agents for Hepatitis C
15.3.1 Ledipasvir/Sofosbuvir
15.3.2 Efficacy and Indication of Ledipasvir/Sofosbuvir
15.3.3 Side Effects and Drug-Drug Interaction of Ledipasvir/Sofosbuvir
15.3.4 Resistance to Ledipasvir/Sofosbuvir
15.3.5 Elbasvir/Grazoprevir
15.3.6 Drug Interactions of Elbasvir/Grazoprevir
15.3.7 Clinical Efficacy of Elbasvir/Grazoprevir
15.3.8 Adverse Effects of Elbasvir/Grazoprevir
15.3.9 Resistance to Elbasvir/Grazoprevir
15.3.10 Sofosbuvir/Velpatasvir
15.3.11 Drug Interactions of Sofosbuvir/Velpatasvir
15.3.12 Efficacy of Sofosbuvir/Velpatasvir
15.3.13 Safety of Sofosbuvir/Velpatasvir
15.3.14 Resistance to Sofosbuvir/Velpatasvir
15.3.15 Glecaprevir/Pibrentasvir
15.3.16 Drug Interactions of Glecaprevir/Pibrentasvir
15.3.17 Efficacy of Glecaprevir/Pibrentasvir
15.3.18 Adverse Effects of Glecaprevir/Pibrentasvir
15.3.19 Resistance to Glecaprevir/Pibrentasvir
15.3.20 Sofosbuvir/Velpatasvir/Voxilaprevir
15.3.21 Drug Interactions of Sofosbuvir/Velpatasvir/Voxilaprevir
15.3.22 Clinical Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir
15.3.23 Safety of Sofosbuvir/Velpatasvir/Voxilaprevir
15.3.24 Resistance to Sofosbuvir/Velpatasvir/Voxilaprevir
15.3.25 Summary
References
Chapter 16: Antiviral Drugs for SARS-CoV-2 and COVID-19
16.1 Introduction
16.2 Coronaviruses
16.3 Antiviral Drugs for SARS-CoV
16.4 Remdesivir
16.4.1 Animal Studies
16.4.2 Clinical Data on Remdesivir
16.4.3 Side Effects and Drug Interactions of Remdesivir
16.4.4 SARS-CoV-2 Resistance to Remdesivir
16.4.5 Molnupiravir
16.4.6 Animal Studies with Molnupiravir
16.4.7 Clinical Efficacy of Molnupiravir
16.4.8 Safety of Molnupiravir
16.4.9 Resistance to Molnupiravir
16.4.10 Nirmatrelvir/Ritonavir
16.4.11 Drug-Drug Interactions of Nirmatrelvir/Ritonavir
16.4.12 Animal Models Treated with Nirmatrelvir/Ritonavir
16.4.13 Clinical Efficacy of Nirmatrelvir/Ritonavir
16.4.14 Side Effects of Nirmatrelvir/Ritonavir
16.4.15 Rebound of COVID-19 after Antiviral Treatment
16.4.16 Resistance to Nirmatrelvir
16.5 Summary and Comments of Antiviral Agents for COVID-19
References
Part V: Future Antimicrobials
Chapter 17: New Promising Antimicrobials in Development and Novel Approaches for Treatment of Infections
17.1 Introduction
17.2 New Antibiotics in Development
17.3 Traditional Antibiotics in Phase 3 Trials Against WHO Priority Pathogens
17.3.1 New Antibiotic Being Developed in Phase 1 and 2 Trials
17.3.2 New Traditional Antibacterial Agents in Phase 1/2 Trials for Mycobacteria Tuberculosis and Nontuberculous Mycobacteria
17.4 Nontraditional Antibacterial Agents in Phase 3 Trials
17.4.1 Nontraditional Antibacterial Agents in Phase 1 and 2
17.5 New Antifungal Agents in Development
17.5.1 Derivatives of Existing Class of Antifungals
17.5.2 Novel Antifungal Agents
17.6 New Anti-Parasitic Agents in Development
17.6.1 New Antimalarial Agents in Development
17.7 New Antivirals in Development
17.7.1 New Antivirals for HIV
17.7.2 New Antivirals for Chronic Hepatitis B
17.8 Summary of New Antimicrobial Agents in Development
References
Index
