The Quinolones

Contributors

Preface


1 The Quinolones: History and Overview

1.1 Mechanism of Action

1.2 Activity In Vitro

1.3 Bacterial Resistance

1.4 Clinical Pharmacology

1.5 Clinical Uses

1.5.1 Genitourinary and Gastrointestinal Infections

1.5.2 Respiratory Tract Infections

1.5.3 Skin and Bone Infections

1.5.4 Other Infections

1.6 Adverse Effects

1.7 Summary

References


2 Chemistry and Mechanisms of Action of the Quinolone Antibacterials 23

2.1 Chemistry

2.2 Target Site

2.3 Selectivity

2.4 Antibacterial Activities

2.5 4-Quinolone Interactions with Ions

2.6 4-Quinolone Interactions with Oxygen

2.7 4-Quinolone Interactions with Other Antibacterials

2.8 Resistance

References


3 In Vitro Properties of the Quinolones

3.1 Gram-Negative Aerobes

3.1.1 Enterobacteriaceae

3.1.2 Other Gram-Negative Aerobes

3.2 Gram-Positive Aerobes

3.3 Anaerobes

3.4 Miscellaneous Organisms

3.5 Development of Resistance

3.6 Conclusion

References


4 Pharmacokinetics of Fluorinated Quinolones

Introduction

4.1 Serum Concentrations

4.2 Urine Concentrations

4.3 Steady State

4.4 Pharmacokinetics

4.5 Elimination

4.6 Bioavailability

4.7 Impaired Renal Function

4.8 Impaired Liver Function

4.9 Impact of Food

4.10 Interactions

4.11 Influence of Disease

4.12 Extravascular Penetration

References


5 Clinical Overview of the Newer 4-Quinolone Antibacterial Agents

Introduction

5.1 Urinary Tract Infections

5.1.1 Pharmacology

5.1.2 Microbiology

5.1.3 Clinical Studies

5.2 Respiratory Tract Infections

5.2.1 Pharmacology

5.2.2 Microbiology

5.2.3 Clinical Studies

5.3 Gastrointestinal Infections

5.3.1 Pharmacology

5.3.2 Microbiology

5.3.3 Clinical Studies

5.4 Skin and Soft-Tissue Infections

5.4.1 Pharmacology

5.4.2 Microbiology

5.4.3 Clinical Studies

5.5 Osteomyelitis

5.5.1 Pharmacology

5.5.2 Microbiology

5.5.3 Clinical Studies

5.6 Sexually Transmitted Diseases

5.6.1 Pharmacology

5.6.2 Microbiology

5.6.3 Clinical Studies

5.7 Immunocomprised Patients

5.8 Central Nervous System Infections

5.8.1 Neisseria Meningitidis Nasopharyngeal Carriers

5.9 Other Potential Uses

5.9.1 Endocarditis

5.9.2 Mycobacteria

5.9.3 Brucellosis

5.10 Summary

References


6 Safety Overview: Toxicity, Adverse Effects and Drug Interactions

6.1 Introduction

6.2 Toxicity of Quinolones

6.2.1 General Remarks

6.2.2 Arthropathy in Laboratory Animals

6.2.3 Renal Tolerability

6.2.4 Testicular Toxicity

6.2.5 Ocular Toxicity

6.2.6 Mutagenicity

6.2.7 Prenatal Toxicity

6.3 Adverse Effects of Fluoroquinolones in Clinical Studies

6.3.1 General Considerations

6.3.2 Gastrointestinal Side-Effects

6.3.3 Side-Effects on the Central Nervous System

6.3.4 Hypersensitivity Reactions

6.3.5 Phototoxicity

6.3.6 Case Reports of Arthralgia During Quinolone Therapy

6.3.7 Other Rarely Registered Side-Effects

6.3.8 Side-Effects Observed in Clinical Trials with Individual Fluoroquinolones

6.3.9 Side-Effects Observed in Comparative Double Blind Studies

6.4 Drug Interactions

6.4.1 General Remarks

6.4.2 Influence of pH and Magnesium on Antibacterial Activity of Quinolones

6.4.3 Interactions Between Quinolones and Antacids

6.4.4 Influence of Antiulcer Drugs and Breakfast on the Bioavailability of Quinolones

6.4.5 Interactions in Renal Elimination

6.4.6 Interactions Between Quinolones and Theophylline

6.4.7 Interactions Between Quinolones and Caffeine

6.4.8 Interactions Between Quinolones and Warfarin

References


7 The Quinolones: Prospects

7.1 Microbiology

7.2 Resistance of Bacteria to Quinolones

7.3 Pharmacology

7.4 Toxicological Issues

7.5 Clinical Considerations for Future Use of Quinolones

7.5.1 Urinary Tract Infections

7.5.2 Sexually Transmitted Diseases

7.5.3 Respiratory Infections

7.5.4 Gastrointestinal Infections

7.5.5 Osteomyelitis

7.5.6 Mycobacterial Infections

7.6 Prophylactic Use of Quinolones

7.7 Summary

References

Index