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232 PART 5 Antiviral Drugs • The PIs pose tremendous drug interaction challenges. They are all substrates of the common drug-metabolizing enzymes and thus can have their concentrations substantially increased or decreased by drugs that inhibit or induce these enzymes. Ritonavir is one of the most potent inhibitors of the cytochrome P450 enzyme system; hence its use in boosting levels of the other PIs (at the boosting doses used, it has minimal direct antiviral effect). Generally, co-administering other drugs that are P450 substrates (such as statins, macrolides, benzodiazepines, and calcium channel blockers) with ritonavir leads to increased serum concentrations of these drugs. However, more unpredictable effects can occur, perhaps as a result of shunting to alternative pathways or mixed inhibition/induction, leading to the reduction in serum levels of P450 substrates (as can be seen with voriconazole and methadone). The bottom line: for patients on PIs, carefully screen all of their medications for drug interactions using the most up-to-date references. • Ritonavir is now used almost exclusively as a pharmacokinetic booster in much lower doses than its originally approved dose of 400 mg BID. It is not well-tolerated at the higher dose and the majority of prescriptions or orders for it are an error. At the least, it warrants a double-check. What They’re Good For Several PI-based combinations are among the preferred regimens for treatment of initial HIV infection. They are also often used in salvage regimens
chapter 35 Antiretroviral Drugs 233 for patients with resistant virus. Their durable viral suppression needs to be balanced against their long-term toxicities (particularly cardiovascular effects), and patients should be prepared to make appropriate lifestyle changes. Don’t Forget! Only atazanavir can be used unboosted (and this is recommended only for selected patients). If there’s not a little ritonavir in the regimen, something is probably wrong.
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Antibiotics Simplified third EDITIO
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Contents Acknowledgments Introducti
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Contents v Chapter 28: Antifungal A
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Acknowledgments Our thanks go to th
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x Introduction ■■ How to Use Th
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New to the Third Edition The Third
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The Wonderful World of Microbiology
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chapter 1 Microbiology 5 More like
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chapter 1 Microbiology 7 Influenza
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chapter 1 Microbiology 9 Bacilli An
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chapter 1 Microbiology 11 Gram-nega
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chapter 1 Microbiology 13 Cocci Aer
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General Approach to Infectious Dise
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chapter 2 Infectious Diseases 17 Th
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chapter 2 Infectious Diseases 19 Su
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chapter 2 Infectious Diseases 21 al
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Antibiotic Pharmacokinetics 3 The t
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chapter 3 Pharmacokinetics 25 Table
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chapter 3 Pharmacokinetics 27 can b
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chapter 3 Pharmacokinetics 29 becau
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chapter 3 Pharmacokinetics 31 Table
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34 PART 1 Antibiotic Therapy No vis
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36 PART 1 Antibiotic Therapy Table
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38 PART 1 Antibiotic Therapy done i
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Adverse Consequences of Antibiotic
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chapter 5 Adverse Consequences 43 f
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chapter 5 Adverse Consequences 45 U
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Antibacterial Drugs Part 2
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50 PART 2 Antibacterial Drugs to be
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52 PART 2 Antibacterial Drugs is ne
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54 PART 2 Antibacterial Drugs Spect
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Antistaphylococcal Penicillins Agen
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Aminopenicillins Agents: amoxicilli
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chapter 6 Beta-Lactams 61 Don’t F
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64 PART 2 Antibacterial Drugs Adver
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66 PART 2 Antibacterial Drugs enhan
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68 PART 2 Antibacterial Drugs good
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70 PART 2 Antibacterial Drugs Cefaz
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72 PART 2 Antibacterial Drugs ■
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Third-Generation Cephalosporins Age
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chapter 6 Beta-Lactams 79 biliary e
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82 PART 2 Antibacterial Drugs but o
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84 PART 2 Antibacterial Drugs bind
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Carbapenems Agents: imipenem/cilast
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chapter 6 Beta-Lactams 89 and thus
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94 PART 2 Antibacterial Drugs Mecha
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96 PART 2 Antibacterial Drugs as be
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98 PART 2 Antibacterial Drugs Spect
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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
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chapter 10 Tetracyclines 107 admini
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Macrolides and Ketolides 11 Agents:
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chapter 11 Macrolides and Ketolides
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Oxazolidinones 12 Agent: linezolid
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chapter 12 Oxazolidinones 115 What
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118 PART 2 Antibacterial Drugs Spec
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Nitrofurans and Fosfomycin 14 Agent
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chapter 14 Nitrofurans and Fosfomyc
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Cyclic Lipopeptides 16 Agent: dapto
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chapter 16 Cyclic Lipopeptides 131
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136 PART 2 Antibacterial Drugs What
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140 PART 2 Antibacterial Drugs Don
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144 PART 2 Antibacterial Drugs Beca
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146 PART 2 Antibacterial Drugs asso
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Antimycobacterial Drugs 21 ■■ I
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chapter 21 Antimycobacterial Drugs
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154 PART 3 Antimycobacterial Drugs
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Pyrazinamide 24 Agent: pyrazinamide
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Ethambutol 25 Agent: ethambutol (EM
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Antifungal Drugs Part 4
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168 PART 4 Antifungal Drugs When th
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Polyenes 27 Agents: amphotericin B,
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chapter 27 Polyenes 173 1.5 mg/kg/d
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Antifungal Antimetabolites 28 Agent
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chapter 28 Antifungal Antimetabolit
Page 195 and 196: Fluconazole The introduction of flu
Page 197: chapter 29 Azoles 183 • The high
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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
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Page 215: Antiviral Drugs Part 5
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Page 221 and 222: Anti-Herpes Simplex Virus and Varic
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Page 229 and 230: Neuraminidase Inhibitors 34 Agents:
Page 231: chapter 34 Neuraminidase Inhibitors
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Page 249 and 250: Integrase Inhibitors Agents: ralteg
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Page 267 and 268: Hepatitis B Nucleoside Analogs 39 A
Page 269: Antiparasitic Drugs Part 6
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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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Page 287 and 288: Pentamidine 44 Agent: pentamidine P
Page 289: chapter 44 Pentamidine 275 as appro
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Page 294 and 295: Appendix 1 Selected Normal Human Fl
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Appendix 2 Spectrum of Activity A N
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284 appendix 2 and thus less likely
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286 appendix 2 Table A-2 Clinically
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Appendix 3 Empiric Regimens for Com
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290 appendix 3 Infection Common Pat
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292 appendix 3 Infection Common Pat
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294 Index Amoxicillin/clavulanate,
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296 Index Broad-spectrum antibacter
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298 Index Combivir, 221 Community-a
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300 Index Eukaryotes, 5, 203 Extend
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302 Index HIV (continued) anti-herp
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304 Index Minimum bactericidal conc
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306 Index PEG. See Polyethylene gly
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308 Index Pseudomonas (continued) P
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310 Index Sustained virologic respo
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