Clinical Use of Anti-infective Agents Robert W. Finberg Roy Guharoy ● Clinical Use of Anti-infective Agents A Guide on How to Prescribe Drugs Used to Treat Infections Robert W. Finberg Roy Guharoy Richard Haidack Professor and Chair Chief Pharmacy Offi cer Department of Medicine UMass Memorial Health Care University of Massachusetts Clinical Professor of Medicine Medical School University of Massachusetts Worcester, MA, USA Medical School [email protected] Worcester, MA, USA [email protected] ISBN 978-1-4614-1067-6 e-ISBN 978-1-4614-1068-3 DOI 10.1007/978-1-4614-1068-3 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011942229 © Springer Science+Business Media, LLC 2012 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identifi ed as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Contents Part I Introduction to Anti-infective Therapy, Structures and Mechanisms of Action of Commonly Used Antibacterial Agents 1 Introduction and History ....................................................................... 3 2 Basic Principles of Drug Delivery and Dosing...................................... 5 Mechanism of Actions of Anti-bacterial Agents ...................................... 5 Role of Pharmacokinetics and Pharmacodynamics in the Management of Bacterial Infectious Diseases ................................ 5 PK/PD Profi les of Anti-microbial Agents ................................................. 9 Time-Dependent Agents (Duration of Exposure to a Specifi c MIC) ..................................................................................... 9 Concentration-Dependent Killing ............................................................. 9 Pharmacokinetic Variability ...................................................................... 10 Renal Impairment ...................................................................................... 10 Hepatic Impairment .................................................................................. 10 Critically Ill Patients ................................................................................. 11 Tissue Concentrations ............................................................................... 12 Bacteriostatic Versus Bactericidal Drugs .................................................. 12 Conclusion ................................................................................................ 13 Further Reading ........................................................................................ 13 3 Sulfonamides............................................................................................ 15 Introduction ............................................................................................... 15 Mechanism of Action ................................................................................ 15 Trimethoprim ............................................................................................ 16 Trimethoprim–Sulfamethoxazole Combinations ...................................... 17 Spectrum of Activity ................................................................................. 18 Common Uses ........................................................................................... 18 Adverse Effects ......................................................................................... 18 Further Reading ........................................................................................ 19 v vi Contents 4 Penicillins ................................................................................................. 21 Introduction ............................................................................................... 21 Mechanism of Action ................................................................................ 21 Classes of Penicillins ................................................................................ 22 Natural Penicillins (Penicillin G and Penicillin V) ............................... 22 Spectrum of Activity ................................................................................. 23 Common Uses ........................................................................................... 23 Anti-staphylococcal Penicillins: Methicillin, Oxacillin, and Nafcillin .............................................................................................. 24 Common Uses for Anti-staphylococcal Penicillins .................................. 25 Aminopenicillins ....................................................................................... 25 Spectrum of Activity of Aminopenicillins ................................................ 26 Common Uses of Aminopenicillins .......................................................... 26 Combinations of Aminopenicillins with Beta-Lactamase Inhibitors ........ 26 Spectrum of Activity of Aminopenicillin/Beta-Lactamase Combinations ............................................................................................ 27 Common Uses for Aminopenicillin/Beta-Lactamase Combinations ............................................................................................ 27 Extended-Spectrum Penicillins ................................................................. 27 Spectrum of Activity of Extended-Spectrum Penicillins .......................... 28 Common Uses of Extended-Spectrum Penicillins .................................... 28 Extended-Spectrum Penicillins Combined with Beta-Lactamase Inhibitors ................................................................................................... 28 Spectrum of Activity of Extended-Spectrum Penicillins Combined with Beta-Lactamases ............................................................................... 29 Common Uses of Extended-Spectrum Penicillin Combined with Beta-Lactamases ............................................................................... 29 Adverse Effects and Toxicities of Penicillins ........................................... 29 Further Reading ........................................................................................ 30 5 Cephalosporins ........................................................................................ 31 Introduction ............................................................................................... 31 Mechanism of Action ................................................................................ 31 Classes of Cephalosporins ........................................................................ 32 Adverse Effects ......................................................................................... 35 Common Uses of Cephalosporins (Table 5.2) .......................................... 36 Further Reading ........................................................................................ 36 6 Monobactams .......................................................................................... 37 Aztreonam ................................................................................................. 37 Introduction ........................................................................................... 37 Mechanism of Action ................................................................................ 37 Spectrum of Activity ................................................................................. 37 Common Uses ........................................................................................... 38 Adverse Effects ......................................................................................... 38 Further Reading ........................................................................................ 39 Contents vii 7 Carbapenems ........................................................................................... 41 Introduction ............................................................................................... 41 Mechanism of Action ................................................................................ 41 Spectrum of Activity ................................................................................. 41 Common Uses ........................................................................................... 42 Adverse Effects ......................................................................................... 43 Imipenem .................................................................................................. 43 Meropenem ............................................................................................... 43 Ertapenem ................................................................................................. 43 Doripenem ................................................................................................. 43 Summary ................................................................................................... 44 Further Reading ........................................................................................ 44 8 Glycopeptides and Other Agents Used to Treat Gram-Positive Cocci ............................................................................... 45 Introduction ............................................................................................... 45 Vancomycin ............................................................................................... 45 Mechanism of Action ................................................................................ 45 Spectrum of Activity ................................................................................. 46 Common Uses ........................................................................................... 46 Adverse Effects ......................................................................................... 47 Teicoplanin ................................................................................................ 47 Dalbavancin and Telavancin ..................................................................... 48 Mechanism of Action ................................................................................ 48 Spectrum of Activity ................................................................................. 48 Common Uses ........................................................................................... 49 Adverse Effects ......................................................................................... 49 Miscellaneous Non-glycopeptide Agents ................................................. 49 Streptogramins ...................................................................................... 49 Quinupristin/Dalfopristin ...................................................................... 49 Mechanism of Action ................................................................................ 49 Spectrum of Activity ................................................................................. 50 Adverse Effects ......................................................................................... 50 Oxazolidinones ......................................................................................... 51 Linezolid ................................................................................................... 51 Mechanism of Action ................................................................................ 51 Spectrum of Activity ................................................................................. 52 Common Uses ........................................................................................... 52 Adverse Effects ......................................................................................... 52 Daptomycin ............................................................................................... 52 Mechanism of Action ................................................................................ 52 Spectrum of Activity ................................................................................. 53 Common Uses ........................................................................................... 53 viii Contents Adverse Effects ......................................................................................... 53 Fidaxomicin .............................................................................................. 54 Mechanism of Action ................................................................................ 54 Spectrum of Activity ................................................................................. 54 Common Uses ........................................................................................... 55 Adverse Effects ......................................................................................... 55 Further Reading ........................................................................................ 55 9 Aminoglycosides ...................................................................................... 57 Introduction ............................................................................................... 57 Mechanism of Action ................................................................................ 57 Spectrum of Activity ................................................................................. 57 Pharmacokinetics ...................................................................................... 58 Traditional Multiple Daily Dosing ............................................................ 58 Single Daily Dose ..................................................................................... 59 Adverse Effects ......................................................................................... 61 Common Uses ........................................................................................... 61 Further Reading ........................................................................................ 62 10 Macrolides................................................................................................ 63 Introduction ............................................................................................... 63 Mechanism of Action ................................................................................ 63 Spectrum of Activity ................................................................................. 63 Erythromycin ........................................................................................ 63 Azithromycin ........................................................................................ 64 Clarithromycin ...................................................................................... 64 Resistance ................................................................................................. 65 Common Uses ........................................................................................... 65 Adverse Effects ......................................................................................... 65 Further Reading ........................................................................................ 66 11 Metronidazole and Clindamycin ........................................................... 67 Introduction ............................................................................................... 67 Mechanism of Action ................................................................................ 67 Spectrum of Activity ................................................................................. 67 Common Uses ........................................................................................... 68 Adverse Effects ......................................................................................... 68 Clindamycin .............................................................................................. 68 Mechanism of Action ................................................................................ 69 Spectrum of Activity ................................................................................. 69 Common Uses ........................................................................................... 69 Adverse Effects ......................................................................................... 70 Further Reading ........................................................................................ 70 Contents ix 12 Quinolones ............................................................................................... 71 Introduction ............................................................................................... 71 Mechanism of Action ................................................................................ 71 Spectrum of Activity ................................................................................. 71 Common Uses ........................................................................................... 73 Adverse Effects ......................................................................................... 73 Conclusion ................................................................................................ 74 Further Reading ........................................................................................ 74 13 Tetracyclines ............................................................................................ 75 Introduction ............................................................................................... 75 Mechanism of Action ................................................................................ 75 Spectrum of Activity ................................................................................. 76 Common Uses ........................................................................................... 77 Adverse Effects ......................................................................................... 77 Further Reading ........................................................................................ 78 Part II The Clinician Approaches a Patient with an Infectious Disease 14 Clinical Approach to the Treatment of Infectious Diseases ................ 81 The Four Questions ................................................................................... 81 Asking the Four Questions .................................................................... 82 The Remainder of the History ................................................................... 83 Specifi c Issues in the Physical Examination ............................................. 83 Use of the Laboratory ............................................................................... 83 15 Understanding Drug Allergies and Drug Toxicities ............................. 85 Antibiotic Allergy ..................................................................................... 85 Classifi cation of Antibiotic Allergy .......................................................... 85 Clinical Features ....................................................................................... 86 Diagnosis of Antibiotic Allergy ................................................................ 86 Other Methods .......................................................................................... 87 Differential Diagnosis ............................................................................... 88 Cross-Reactivity Between Cephalosporins and Penicillins ...................... 88 Cross-Reactivity Among Cephalosporins ................................................. 88 Penicillin Allergy and Carbapenems......................................................... 90 Penicillin and Monobactams ..................................................................... 90 Sulfonamide Allergy ................................................................................. 91 Nonsulfonylarylamines ......................................................................... 91 Drugs in Which the Sulfonamide Moiety Is Not Connected to the Benzene Ring .............................................................................. 91 Sulfonylarylamine Drugs ...................................................................... 92