Antibiotics Simplified third EDITION Jason C. Gallagher PharmD, BCPS Conan MacDougall PharmD, MAS, BCPS Clinical Associate Professor Temple University Associate Professor of Clinical Pharmacy School of Pharmacy University of California San Francisco San Francisco, CA Adjunct Assistant Professor of Pharmacology and Physiology School of Medicine Drexel University Philadelphia, PA
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Contents Acknowledgments Introduction New to the Third Edition vii ix xiii Part 1: Considerations with Antibiotic Therapy 1 Chapter 1: The Wonderful World of Microbiology 3 Chapter 2: General Approach to Infectious Diseases 15 Chapter 3: Antibiotic Pharmacokinetics 23 Chapter 4: Antibiotic Pharmacodynamics 33 Chapter 5: Adverse Consequences of Antibiotic Use 41 Part 2: Antibacterial Drugs 47 Chapter 6: Beta-Lactams 49 Penicillins 51 Natural Penicillins 53 Antistaphylococcal Penicillins 57 Aminopenicillins 59 Antipseudomonal Penicillins 63 Beta-Lactamase Inhibitor Combinations 65 Cephalosporins 69 First-Generation Cephalosporins 71 Second-Generation Cephalosporins 73 iii
iv Contents Third-Generation Cephalosporins 77 Fourth-Generation Cephalosporins 81 Fifth-Generation Cephalosporins 83 Carbapenems 87 Monobactams 91 Chapter 7: Glycopeptides 93 Chapter 8: Fluoroquinolones 97 Chapter 9: Aminoglycosides 101 Chapter 10: Tetracyclines and Glycylcyclines 105 Chapter 11: Macrolides and Ketolides 109 Chapter 12: Oxazolidinones 113 Chapter 13: Nitroimidazoles 117 Chapter 14: Nitrofurans and Fosfomycin 121 Chapter 15: Streptogramins 125 Chapter 16: Cyclic Lipopeptides 129 Chapter 17: Folate Antagonists 133 Chapter 18: Lincosamides 137 Chapter 19: Polymyxins 141 Chapter 20: Fidaxomicin 145 PART 3: Antimycobacterial Drugs 147 Chapter 21: Antimycobacterial Drugs 149 Chapter 22: Rifamycins 153 Chapter 23: Isoniazid 157 Chapter 24: Pyrazinamide 161 Chapter 25: Ethambutol 163 PART 4: Antifungal Drugs 165 Chapter 26: Antifungal Drugs 167 Chapter 27: Polyenes 171
Contents v Chapter 28: Antifungal Antimetabolites 175 Chapter 29: Azoles 179 Fluconazole 181 Itraconazole 185 Voriconazole 189 Posaconazole 193 Chapter 30: Echinocandins 197 PART 5: Antiviral Drugs 201 Chapter 31: Antiviral Drugs 203 Chapter 32: Anti-Herpes Simplex Virus and Varicella-Zoster Virus Agents 207 Chapter 33: Anti-Cytomegalovirus Agents 211 Chapter 34: Neuraminidase Inhibitors 215 Chapter 35: Antiretroviral Drugs 219 Nucleoside and Nucleotide Reverse Transcriptase Inhibitors 221 Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 225 Protease Inhibitors 229 Integrase Inhibitors 235 Entry and Fusion Inhibitors 239 Chapter 36: Antiviral Interferons 241 Chapter 37: Serine Protease Inhibitors 245 Chapter 38: Ribavirin 249 Chapter 39: Hepatitis B Nucleoside Analogs 253 PART 6: Antiparasitic Drugs 255 Chapter 40: Antiparasitic Drugs 257 Chapter 41: Quinolines 261 Chapter 42: Atovaquone 265
vi Contents Chapter 43: Benzimidazoles 269 Chapter 44: Pentamidine 273 Chapter 45: Ivermectin 277 Appendix 1: Selected Normal Human Flora 280 Appendix 2: Spectrum of Activity 282 Appendix 3: Empiric Regimens for Common Infections 288 Index 293
Acknowledgments Our thanks go to those who helped edit all three editions of Antibiotics Simplified, and to our wives, who put up with us and took care of our kids while we wrote the Third Edition. We dedicate this text to the pharmacy students of Temple University and University of California San Francisco. We hope you find it useful. vii
Introduction Antibiotics the word sends terror coursing through the veins of students and makes many healthcare professionals uncomfortable. The category of antibiotics actually contains many different classes of drugs that differ in spectrum of activity, adverse effect profiles, pharmacokinetics and pharmacodynamics, and clinical utility. These classes can seem bewildering and beyond comprehension. We believe that taking a logical, stepwise approach to learning the pharmacotherapy of infectious diseases can help burn away the mental fog preventing optimal use and understanding of these drugs. Learning the characteristics of antibiotics greatly simplifies learning infectious disease pharmacotherapy. Students and clinicians who attempt to learn the antibiotics of choice for different types of infections before knowing the characteristics of those drugs never truly understand the context of what they are attempting to learn. Once the characteristics of the antibiotics are known, making a logical choice to treat an infection is much easier. This approach takes some time up front, but it will be well worth the effort when one realizes that the pharmacotherapy of all infections is fundamentally similar and logical. ix
x Introduction How to Use This Book We wrote this book in an effort to condense the many facts that are taught about antibiotics in pharmacology and pharmacotherapy courses into one quick reference guide. It is meant to supplement material learned in pharmacology, not to supplant it. Use this book as a reference when you encounter a class of antibiotics that you know you have heard about; it will remind you of key points you may have forgotten. This book contains six parts. Part 1 reviews basic microbiology and how to approach the pharmacotherapy of a patient with a presumed infection. The chapters in Parts 2 6 provide concise reviews of various classes of antibacterial, antimycobacterial, antifungal, antiviral, and antiparasitic drugs. Again, this book is intended to supplement your other pharmacology textbooks. These chapters give key points about each class of antibiotics they are not thorough reviews. The appendices contain references that may help in daily use. Format of the Drug Class Reviews Each drug class chapter follows the same basic format. The agents belonging to each class are listed first. The drugs used most commonly in practice are bolded. Mechanism of Action This section concisely summarizes the mechanism of action of the antibiotic class. Spectrum This section summarizes key organisms against which each class has or lacks activity. The spectra listed are not exhaustive.
Introduction xi Adverse Effects This section lists key adverse effects. This list is not exhaustive, but it gives the most common and/or concerning adverse effects of each class. Dosing Issues This section discusses common problems or potential errors in drug dosing for select drug classes. Important Facts This section provides a summary of significant facts for and aspects of each drug class. What They re Good For This section lists some of the most common and/or useful indications for the agents in the class. Often the agents discussed have not been approved for these indications by the U.S. Food and Drug Administration (FDA), but they are commonly used for them anyway. Conversely, many FDA indications that the antibiotics do have are not listed here, because they are often out-of-date. Don t Forget! In this section, we list points that are often overlooked or especially important when dealing with the drug class. As you read this book, try to think of situations in which the antibiotics would be useful to your patients. Think of why an antibiotic is useful for an indication; don t just learn that it is. It is our sincere hope that you too have that magic moment where the world of antibiotics and the study of infectious diseases click together. Let us know when it happens.
New to the Third Edition The Third Edition of Antibiotics Simplified expands on the drug classes covered in the first while retaining the key point focus of the text that has made it successful. The Third Edition includes expanded coverage of antiviral agents, particularly new-andold treatments for hepatitis B and C infections. New antibiotics have been added since the Second Edition, and the chapters for each class were updated with new clinical and scientific findings. xiii