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30 PART 1 Antibiotic Therapy be anticipated based on blood concentrations. For example, the concentrations of nitrofurantoin achieved in the blood and tissues are generally inadequate to inhibit bacterial growth. However, it is removed from the bloodstream by the kidneys and accumulates in the bladder until its, ahem, final clearance. The concentrations achieved in the bladder are many-fold higher than those in the bloodstream, making nitrofurantoin an effective drug for treatment of bladder infections. When the body does not inactivate the drug, an important consideration is to appropriately reduce the administered dose of the drug if there is damage to the organ responsible for excreting the drug. The most common example of this for antibiotics is the need to reduce the doses of most beta-lactams for patients with kidney dysfunction, to avoid accumulation of toxic levels of the drug. Other drugs may be extensively transformed by the body prior to their excretion. These antibiotics that undergo extensive metabolism are considered to be substrates of drug metabolizing enzymes. They have the potential to be subject to clinically important drug interactions, as other drugs may interfere with the enzymes that break the drugs down. Moreover, certain antibiotics have the potential to influence the metabolism of other drugs, either through inhibition of those enzymes (leading to a decrease in metabolism of the other drug) or induction (leading to an increase in metabolism of the other drug). A list of antibiotics with the greatest likelihood of clinically significant metabolic drug interactions is in Table 3–3 , organized by whether the drug is a substrate, inhibitor,
chapter 3 Pharmacokinetics 31 Table 3–3 Examples of Antibiotics with Significant Metabolic Drug Interactions Substrates Inhibitors Inducers Erythromycin Clarithromycin Telithromycin Atazanavir Darunavir Efavirenz Elvitegravir Maraviroc Rilpivirine TMP/SMX Metronidazole Fluconazole Voriconazole Itraconazole Posaconazole Erythromycin Clarithromycin Telithromycin Ritonavir Cobicistat Etravirine Rifampin Rifabutin Efavirenz Nevirapine Etravirine or inducer (and note that drugs may be in more than one category). Note that the several antibiotic classes are particularly prevalent: macrolides, azole antifungals, antituberculosis drugs, and antiretrovirals account for most of the antibiotics with significant drug interactions. Complex drug interactions can occur with these drugs: for example, the antiretroviral drug etravirine is simultaneously a substrate, an inhibitor, and an inducer of drug-metabolizing enzymes!
Page 1 and 2: Antibiotics Simplified third EDITIO
Page 3 and 4: Contents Acknowledgments Introducti
Page 5 and 6: Contents v Chapter 28: Antifungal A
Page 7: Acknowledgments Our thanks go to th
Page 10 and 11: x Introduction ■■ How to Use Th
Page 13: New to the Third Edition The Third
Page 17 and 18: The Wonderful World of Microbiology
Page 19 and 20: chapter 1 Microbiology 5 More like
Page 21 and 22: chapter 1 Microbiology 7 Influenza
Page 23 and 24: chapter 1 Microbiology 9 Bacilli An
Page 25 and 26: chapter 1 Microbiology 11 Gram-nega
Page 27 and 28: chapter 1 Microbiology 13 Cocci Aer
Page 29 and 30: General Approach to Infectious Dise
Page 31 and 32: chapter 2 Infectious Diseases 17 Th
Page 33 and 34: chapter 2 Infectious Diseases 19 Su
Page 35 and 36: chapter 2 Infectious Diseases 21 al
Page 37 and 38: Antibiotic Pharmacokinetics 3 The t
Page 39 and 40: chapter 3 Pharmacokinetics 25 Table
Page 41 and 42: chapter 3 Pharmacokinetics 27 can b
Page 43: chapter 3 Pharmacokinetics 29 becau
Page 48 and 49: 34 PART 1 Antibiotic Therapy No vis
Page 50 and 51: 36 PART 1 Antibiotic Therapy Table
Page 52 and 53: 38 PART 1 Antibiotic Therapy done i
Page 55 and 56: Adverse Consequences of Antibiotic
Page 57 and 58: chapter 5 Adverse Consequences 43 f
Page 59 and 60: chapter 5 Adverse Consequences 45 U
Page 61: Antibacterial Drugs Part 2
Page 64 and 65: 50 PART 2 Antibacterial Drugs to be
Page 66 and 67: 52 PART 2 Antibacterial Drugs is ne
Page 68 and 69: 54 PART 2 Antibacterial Drugs Spect
Page 71 and 72: Antistaphylococcal Penicillins Agen
Page 73 and 74: Aminopenicillins Agents: amoxicilli
Page 75: chapter 6 Beta-Lactams 61 Don’t F
Page 78 and 79: 64 PART 2 Antibacterial Drugs Adver
Page 80 and 81: 66 PART 2 Antibacterial Drugs enhan
Page 82 and 83: 68 PART 2 Antibacterial Drugs good
Page 84 and 85: 70 PART 2 Antibacterial Drugs Cefaz
Page 86 and 87: 72 PART 2 Antibacterial Drugs ■
Page 88 and 89: 74 PART 2 Antibacterial Drugs Adver
Page 91 and 92: Third-Generation Cephalosporins Age
Page 93: chapter 6 Beta-Lactams 79 biliary e
Page 96 and 97:
82 PART 2 Antibacterial Drugs but o
Page 98 and 99:
84 PART 2 Antibacterial Drugs bind
Page 100 and 101:
Carbapenems Agents: imipenem/cilast
Page 102:
chapter 6 Beta-Lactams 89 and thus
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92 PART 2 Antibacterial Drugs Adver
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94 PART 2 Antibacterial Drugs Mecha
Page 109 and 110:
96 PART 2 Antibacterial Drugs as be
Page 111 and 112:
98 PART 2 Antibacterial Drugs Spect
Page 113 and 114:
chapter 9 Aminoglycosides 103 equal
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Aminoglycosides 9 Agents: gentamici
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chapter 9 Aminoglycosides 103 equal
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Tetracyclines and Glycylcyclines 10
Page 121 and 122:
chapter 10 Tetracyclines 107 admini
Page 123 and 124:
Macrolides and Ketolides 11 Agents:
Page 125 and 126:
chapter 11 Macrolides and Ketolides
Page 127 and 128:
Oxazolidinones 12 Agent: linezolid
Page 129:
chapter 12 Oxazolidinones 115 What
Page 132 and 133:
118 PART 2 Antibacterial Drugs Spec
Page 135 and 136:
Nitrofurans and Fosfomycin 14 Agent
Page 137:
chapter 14 Nitrofurans and Fosfomyc
Page 140 and 141:
Page 143 and 144:
Cyclic Lipopeptides 16 Agent: dapto
Page 145:
chapter 16 Cyclic Lipopeptides 131
Page 148 and 149:
Page 150 and 151:
136 PART 2 Antibacterial Drugs What
Page 152 and 153:
Page 154 and 155:
140 PART 2 Antibacterial Drugs Don
Page 156 and 157:
Page 158 and 159:
144 PART 2 Antibacterial Drugs Beca
Page 160 and 161:
146 PART 2 Antibacterial Drugs asso
Page 163 and 164:
Antimycobacterial Drugs 21 ■■ I
Page 165:
chapter 21 Antimycobacterial Drugs
Page 168 and 169:
154 PART 3 Antimycobacterial Drugs
Page 170 and 171:
Page 172 and 173:
Page 175 and 176:
Pyrazinamide 24 Agent: pyrazinamide
Page 177 and 178:
Ethambutol 25 Agent: ethambutol (EM
Page 179:
Antifungal Drugs Part 4
Page 182 and 183:
168 PART 4 Antifungal Drugs When th
Page 185 and 186:
Polyenes 27 Agents: amphotericin B,
Page 187 and 188:
chapter 27 Polyenes 173 1.5 mg/kg/d
Page 189 and 190:
Antifungal Antimetabolites 28 Agent
Page 191:
chapter 28 Antifungal Antimetabolit
Page 195 and 196:
Fluconazole The introduction of flu
Page 197:
chapter 29 Azoles 183 • The high
Page 200 and 201:
186 PART 4 Antifungal Drugs Adverse
Page 203 and 204:
Voriconazole The introduction of vo
Page 205 and 206:
chapter 29 Azoles 191 ■■ Import
Page 207 and 208:
Posaconazole Posaconazole is the ne
Page 209:
chapter 29 Azoles 195 inhibitors lo
Page 212 and 213:
198 PART 4 Antifungal Drugs Spectru
Page 215:
Antiviral Drugs Part 5
Page 218 and 219:
204 PART 5 Antiviral Drugs The unde
Page 221 and 222:
Anti-Herpes Simplex Virus and Varic
Page 223:
chapter 32 Anti-HSV and VZV Agents
Page 226 and 227:
212 PART 5 Antiviral Drugs Spectrum
Page 229 and 230:
Neuraminidase Inhibitors 34 Agents:
Page 231:
chapter 34 Neuraminidase Inhibitors
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220 PART 5 Antiviral Drugs the comm
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Page 238 and 239:
224 PART 5 Antiviral Drugs What The
Page 240 and 241:
226 PART 5 Antiviral Drugs Adverse
Page 242 and 243:
228 PART 5 Antiviral Drugs • NNRT
Page 244 and 245:
230 PART 5 Antiviral Drugs The drug
Page 246 and 247:
232 PART 5 Antiviral Drugs • The
Page 249 and 250:
Integrase Inhibitors Agents: ralteg
Page 251:
chapter 35 Antiretroviral Drugs 237
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240 PART 5 Antiviral Drugs from hea
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Page 258 and 259:
244 PART 5 Antiviral Drugs option f
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246 PART 5 Antiviral Drugs Think of
Page 262 and 263:
248 PART 5 Antiviral Drugs ribaviri
Page 264 and 265:
250 PART 5 Antiviral Drugs administ
Page 267 and 268:
Hepatitis B Nucleoside Analogs 39 A
Page 269:
Antiparasitic Drugs Part 6
Page 272 and 273:
258 PART 6 Antiparasitic Drugs Tabl
Page 275 and 276:
Quinolines 41 Agents: chloroquine,
Page 277 and 278:
chapter 41 Quinolines 263 majority
Page 279 and 280:
Atovaquone 42 Agents: atovaquone, a
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chapter 42 Atovaquone 267 Don’t F
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270 PART 6 Antiparasitic Drugs Adve
Page 287 and 288:
Pentamidine 44 Agent: pentamidine P
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chapter 44 Pentamidine 275 as appro
Page 292 and 293:
278 PART 6 Antiparasitic Drugs Spec
Page 294 and 295:
Appendix 1 Selected Normal Human Fl
Page 296 and 297:
Appendix 2 Spectrum of Activity A N
Page 298 and 299:
284 appendix 2 and thus less likely
Page 300 and 301:
286 appendix 2 Table A-2 Clinically
Page 302 and 303:
Appendix 3 Empiric Regimens for Com
Page 304 and 305:
290 appendix 3 Infection Common Pat
Page 306 and 307:
292 appendix 3 Infection Common Pat
Page 308 and 309:
294 Index Amoxicillin/clavulanate,
Page 310 and 311:
296 Index Broad-spectrum antibacter
Page 312 and 313:
298 Index Combivir, 221 Community-a
Page 314 and 315:
300 Index Eukaryotes, 5, 203 Extend
Page 316 and 317:
302 Index HIV (continued) anti-herp
Page 318 and 319:
304 Index Minimum bactericidal conc
Page 320 and 321:
306 Index PEG. See Polyethylene gly
Page 322 and 323:
308 Index Pseudomonas (continued) P
Page 324 and 325:
310 Index Sustained virologic respo
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