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ANTIBIOTIC ESSENTIALS Fourteenth Edition Edited by Burke A. Cunha, MD, MACP Chief, Infectious Disease Division Winthrop-University Hospital Mineola, New York Professor of Medicine State University of New York School of Medicine Stony Brook, New York The Health Sciences Publisher New Delhi | London | Philadelphia | Panama Jaypee Brothers Medical Publishers Pvt. Ltd. Headquarters Jaypee Brothers Medical Publishers (P) Ltd 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 Email: [email protected] Overseas Offices J.P. 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All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. Inquiries for bulk sales may be solicited at: [email protected] Antibiotic Essentials Fourteenth Edition:  2015 ISBN 978-93-5152-850-0 Printed at ABOUT THE EDITOR Burke A. Cunha, MD, MACP, is Chief, Infectious Disease Division at Winthrop-University Hospital, Mineola, New York; Professor of Medicine, State University of New York School of Medicine, Stony Brook, New York; and is one of the world’s leading authorities on infectious diseases. During his career, he has written/edited over 1250 articles, 200 book chapters, and 30 books on infectious diseases. He has received numerous teaching awards, including the Aesculapius Award for teaching excellence and the Spatz Award for clinical excellence and teaching excellence. Dr. Cunha is a Fellow of the Infectious Disease Society of America, American Academy of ­Microbiology, American College of Clinical Pharmacology, Surgical Infection ­ Society, American College of Chest Physicians and Society of Hospital Epidemiologists of America. He has had a long interest in clinical syndromic diagnosis, diagnostic reasoning, antimicrobial therapy and resistance, atypical pneumonias, surgical infections, infections in compromised hosts, zoonoses, FUOs, meningitis and encephalitis, endocarditis, and nosocomial infections. Dr. Cunha is a Master of the American College of Physicians, awarded for lifetime achievement as a Master Clinician and Master Teacher of Infectious Diseases. DEDICATION for Marie “Grace in her steps, Heaven in her eye, In every gesture, dignity and love” Milton iv Antibiotic Essentials TABLE OF CONTENTS 1.  VERVIEW OF ANTIMICROBIAL O THERAPY 1 Factors in Antibiotic Selection....................................2 Spectrum.............................................................................2 Tissue Penetration.........................................................2 Antibiotic Resistance...................................................2 Safety Profile......................................................................4 Cost.........................................................................................4 Factors in Antibiotic Dosing.........................................4 Dosing in Renal/Hepatic Insufficiency.............5 Routes of Elimination (Renal and Hepatic)....5 Microbiology and Susceptibility Testing..............6 In Vitro vs. In Vivo Susceptibility............................7 PK/PD and Other Considerations in Anti­microbial Therapy.....................................................9 Bactericidal vs. Bacteriostatic Therapy..............9 Monotherapy vs. Combination Therapy..........9 Intravenous vs. Oral Switch Therapy............... 10 Bioavailability of Oral Antibiotics....................... 11 OPAT.................................................................................... 11 Duration of Therapy.................................................. 11 Empiric vs. Specific Antibiotic Therapy ............. 12 Positive Blood Cultures vs. Bacteremia (MSSA, MRSA, CoNS)................................................. 13 Drug Fever............................................................................ 13 Relative Bradycardia....................................................... 14 Antibiotic Failure.............................................................. 14 Pitfalls in Antibiotic Prescribing............................... 15 2.  MPIRIC THERAPY BASED ON CLINICAL E SYNDROME 17 CNS Infections Acute Bacterial Meningitis......................................... 18 Acute Nonbacterial/Chronic Meningitis........... 21 Encephalitis......................................................................... 25 Brain Abscess/Subdural Empyema/ Cavernous Vein Thrombosis/Intracranial Suppurative Thrombophlebitis.......................... 27 HEENT Infections Facial/Periorbital Cellulitis........................................... 29 Bacterial Sinusitis.............................................................. 30 Keratitis................................................................................... 31 Conjunctivitis...................................................................... 32 Chorioretinitis..................................................................... 34 Endophthalmitis............................................................... 35 External Otitis..................................................................... 37 Acute Otitis Media........................................................... 38 Mastoiditis............................................................................ 39 Suppurative Parotitis...................................................... 40 Pharyngitis............................................................................ 40 Thrush (Oropharyngeal Candidiasis)................... 43 Mouth Ulcers/Vesicles.................................................. 44 Deep Neck Infections, Lemierre’s Syndrome, Severe Dental Infections.............. 46 Epiglottitis............................................................................. 47 Lower Respiratory Tract Infections Acute Bacterial Exacerbation of Chronic Bronchitis........................................................ 48 Mediastinitis........................................................................ 49 Community-Acquired Pneumonia....................... 49 Zoonotic Atypical Pneumonia................................. 60 Lung Abscess/Empyema............................................ 67 Nursing Home-Acquired Pneumonia................. 68 Nosocomial Pneumonia.............................................. 68 Cardiovascular Infections Subacute Bacterial Endocarditis............................. 70 Acute Bacterial Endocarditis..................................... 74 Prosthetic Valve Endocarditis................................... 76 Pericarditis/Myocarditis................................................ 78 Central IV Line/Pacemaker Infections................. 79 Vascular Graft Infections.............................................. 82 Gastrointestinal Tract Infections Esophagitis........................................................................... 84 Peptic Ulcer Disease....................................................... 85 Gastric Perforation........................................................... 85 Diarrhea/Typhoid (Enteric) Fever.............................. 86 Cholecystitis........................................................................ 92 Cholangitis........................................................................... 93 Gallbladder Wall Abscess/Perforation................. 93 Acute Pancreatitis............................................................ 94 Pancreatic Abscess/Infected Pancreatic P ­ seudocyst..................................................................... 95 Liver Abscess...................................................................... 95 Hepatosplenic Candidiasis......................................... 96 Granulomatous Hepatitis............................................ 96 Viral Hepatitis...................................................................... 97 Intraabdominal or Pelvic Peritonitis/ ­ Abscess (Colitis, Appendicitis, ­ D ­ iverticulitis, Septic Pelvic ­ Thrombophlebitis, Spontaneous B ­ acterial Peritonitis, CAPD-Associated P ­ eritonitis, TB Peritonitis)..................................... 100 Table of Contents Genitourinary Tract Infections Dysuria-Pyuria Syndrome........................................ 103 Cystitis.................................................................................. 103 Catheter-Associated Bacteriuria/Candiduria........104 Epididymitis...................................................................... 106 Acute Pyelonephritis................................................... 107 Chronic Pyelonephritis.............................................. 108 Renal TB............................................................................... 108 Renal Abscess (Intrarenal/Perinephric)........... 109 Prostatitis/Prostatic Abscess................................... 110 Urosepsis............................................................................ 111 Pelvic Inflammatory Disease, Salpingitis, T ­ uboovarian Abscess, Endometritis/­ Endomyometritis, Septic Abortion............... 113 Sexually Transmitted Diseases Urethritis/Cervicitis........................................................ 114 Vaginitis/Balanitis............................................................ 115 Genital Vesicles................................................................. 116 Genital Ulcers.................................................................... 117 Suppurating Inguinal Adenopathy..................... 118 Genital/Perianal Warts................................................. 118 Syphilis................................................................................... 119 Bone and Joint Infections Septic Arthritis/Bursitis................................................ 121 Lyme Disease/Lyme Arthritis................................... 127 Infected Joint Prosthesis............................................ 128 Osteomyelitis..................................................................... 129 Skin and Soft Tissue Infections Cellulitis, Erysipelas, Mastitis.................................... 132 Complicated Skin/Skin Structure Infections (cSSSIs)...................................................... 134 Skin Ulcers........................................................................... 137 Skin Abscesses/Infected Cysts (Skin Pustules/Boils, Furunculosis).............................. 140 Skin Vesicles (Non-Genital)....................................... 142 Wound Infections........................................................... 144 Superficial Fungal Infections Skin/Nail.............. 147 Skin Infestations............................................................... 150 Ischiorectal/Perirectal Abscess............................... 151 Sepsis/Septic Shock 151 Febrile Neutropenia 158 Transplant Infections Bacteremia.......................................................................... 160 Candidemia........................................................................ 161 CMV/HHV-6/BK Virus..................................................... 162 EVB/PTLD............................................................................. 163 RSV........................................................................................... 163 Adenovirus.......................................................................... 163 Encephalitis/Meningitis.............................................. 164 v Brain Abscess/Mass Lesions..................................... 164 Focal/Segmental Pulmonary Infiltrates......................................................................... 165 Diffuse Pulmonary Infiltrates................................... 165 Viral Hepatitis..................................................................... 166 Toxin-Mediated Infectious Diseases Toxic Shock Syndrome................................................ 169 Botulism................................................................................ 170 Tetanus.................................................................................. 170 Diphtheria........................................................................... 170 Bioterrorist Agents Anthrax.................................................................................. 173 Tularemia Pneumonia.................................................. 173 Pneumonic Plague......................................................... 174 Botulism................................................................................ 174 Smallpox............................................................................... 174 Ebola....................................................................................... 174 3. ANTIBIOTIC ­SUSCEPTIBILITY ­PROFILES  AND INITIAL ­THERAPY OF ISOLATES PENDING ­SUSCEPTIBILITY RESULTS 185 Antibiotic Susceptibility Profiles (Penicillins, Macrolides, Tetracyclines, and Others)......... 186 Antibiotic Susceptibility Profiles (Cephalosporins)........................................................ 191 Antibiotic Susceptibility Profiles (Aminoglycosides, Fluoroquinolones, Carbapenems, and Others)................................. 198 Gram Stain Characteristics of Isolates (by Morphology Arrangement, Oxygen Requirements).......................................... 203 Alphabetical Index of Isolates................................. 205 Key Factors in Antibiotic Selection (Isolate Known)............................................................................. 207 Antibiotic Resistance Potential............................... 207 Aerobic Isolates................................................................ 208 Capnophilic Isolates...................................................... 235 Anaerobic Isolates.......................................................... 236 Yeast/Fungi......................................................................... 242 Gram Stain/Giemsa Stain Technique.................. 246 CSF Gram Stain................................................................. 246 Sputum Gram Stain....................................................... 248 Urine Gram Stain............................................................. 248 Fecal Gram Stain.............................................................. 249 4. PARASITES, FUNGI, UNUSUAL ­ ORGANISMS 253 Blood Pathogens Microfilaria in Blood...................................................... 254 Trypanosomes in Blood.............................................. 255 Spirochetes in Blood..................................................... 257 Intracellular Inclusion Bodies in Blood.............. 258 vi Antibiotic Essentials CSF/Brain Pathogens Cysts/Mass Lesions in CSF/Brain............................ 261 Lung Pathogens Pulmonary Cystic Lesions/Masses........................ 265 Pulmonary Coin Lesions............................................. 266 Pulmonary Infiltrates/Mass Lesions..................... 267 Heart Pathogens Chagas’ Disease................................................................ 273 Liver Pathogens Liver Flukes.......................................................................... 273 Cystic Masses in Liver................................................... 274 Hepatomegaly.................................................................. 275 Stool/Intestines Pathogens Intestinal Protozoa......................................................... 276 Intestinal Nematodes (Roundworms)................ 278 Intestinal Cestodes (Tapeworms)......................... 281 Intestinal Trematodes (Flukes/Flatworms)................................................... 282 Other Intestinal Infections......................................... 282 Skin/Muscle Pathogens Infiltrative Skin/­ ubcutaneous Lesions........... 283 S Infiltrative Skin Lesions ± Ulcers/Sinus Tracts/Abscesses...................................................... 284 Skin Vesicles/Bullae...................................................... 288 Subcutaneous Serpiginous Lesions.................. 288 Skin Papules/Nodules/Abscesses....................... 289 Rickettsia (Fever/Petechial Skin Rash).............. 294 Other Skin Lesions........................................................ 297 Myositis............................................................................... 298 5. HIV INFECTION 301 Overview ........................................................................... 302 Stages of HIV Infection.............................................. 303 Acute (Primary) HIV Infection................................ 304 Approach to HIV Testing........................................... 305 Initial Assessment of HIV Patients...............................308 Indications for Treatment of HIV Infection........................................................................ 312 Antiretroviral Treatment............................................ 313 Antiretroviral Treatment Failure............................ 316 Opportunistic Infections in HIV Disease......... 319 Treatment of Opportunistic Infections............ 323 Treatment of Other Opportunistic Infections in HIV........................................................ 338 HIV Coinfections (HBV/HCV).................................. 344 6. PROPHYLAXIS AND IMMUNIZATIONS 353 Surgical Prophylaxis..................................................... 354 Post-Exposure Prophylaxis...................................... 358 Chronic Medical Prophylaxis/Suppression..........364 HIV Pre-Exposure Prophylaxis (PrEP).........................365 HIV Post-Exposure Prophylaxis (PEP)........................366 HIV Opportunistic Infections..........................................366 Transplant Prophylaxis........................................................367 Endocarditis Prophylaxis........................................... 369 Travel Prophylaxis.......................................................... 371 Malaria Prophylaxis...................................................... 375 Tetanus Prophylaxis..................................................... 377 Immunizations................................................................ 378   7.  EDIATRIC INFECTIOUS DISEASES P AND PEDIATRIC DRUG SUMMARIES 386  CNS Infections............................................................... 387  HEENT Infections......................................................... 391  Lower Respiratory Tract Infections................... 396  Vascular Infections...................................................... 402  Gastrointestinal Infections..................................... 403  Bone and Joint Infections...................................... 407  Skin and Soft Tissue Infections............................ 411  Common Pediatric Antimicrobial Drugs........414   8. CHEST X-RAY ATLAS 425  Unilateral Focal Segmental/Lobar Infiltrate ­ Without Effusion.....................................................................426  Unilateral Focal Segmental/Lobar Infiltrate With Effusion........................................ 431  Unilateral Ill-Defined Infiltrates Without ­Effusion ....................................................................... 436  Unilateral Ill-Defined Infiltrates With Effusion ..................................................................................443  Bilateral Infiltrates Without Effusion ................ 448  Bilateral Infiltrates With Effusion ....................... 458  Cavitary Infiltrates (Thick-Walled) ..................... 463  Cavitary Infiltrates (Thin-Walled) ...................... 470   9. INFECTIOUS DISEASE DIFFERENTIAL  DIAGNOSIS 474 10. ANTIBIOTIC PEARLS & PITFALLS  507 11. ANTIMICROBIAL DRUG SUMMARIES 521 APPENDIX 720 INDEX 731 COLOR ATLAS OF CSF, SPUTUM, AND URINE GRAM STAINS & FUNGAL STAINS vii EDITORS Burke A. Cunha, MD, MACP Editor Cheston B. Cunha, MD Associate Editor CONTRIBUTORS Burke A. Cunha, MD, MACP Chief, Infectious Disease Division Winthrop-University Hospital Mineola, New York Professor of Medicine State University of New York School of Medicine Stony Brook, New York All chapters except HIV Infection & Pediatric ID Jeffrey Baron, PharmD Clinical Pharmacist Winthrop-University Hospital Mineola, New York HBV, HCV, and HIV Guidelines Antimicrobial Drug Summaries Edward J. Bottone, PhD Professor of Medicine Professor of Microbiology Professor of Pathology Mount Sinai School of Medicine New York, New York Medical Microbiology; Parasites, Fungi, Unusual Organisms John L. Brusch, MD Associate Chief of Medicine Cambridge Health Alliance Infectious Disease Service Cambridge Health Alliance Medical Director, Somerville Hospital Assistant Professor of Medicine Harvard Medical School Boston, Massachusetts Endocarditis: Therapy & Prophylaxis Cheston B. Cunha, MD Director, Antibiotic Stewardship Program Rhode Island Hospital and The Miriam Hospital Infectious Disease Division Assistant Professor of Medicine Brown University Alpert School of Medicine Providence, Rhode Island Infectious Disease Differential Diagnosis Overview of Antimicrobial Therapy Empiric Therapy Based of Clinical Syndromes Antimicrobial Drug Summaries Daniel Caplivski, MD Infectious Disease Division Assistant Professor of Medicine Mt. Sinai School of Medicine New York, New York Fungal Stain Atlas Dennis J. Cleri, MD St. Francis Medical Center Professor of Medicine Seton Hall University School of Graduate Medical Education Trenton, New Jersey Bioterrorism Staci A. Fischer, MD Director, Transplant Infectious Diseases Rhode Island Hospital Infectious Disease Division Associate Professor of Medicine Brown University Alpert School of Medicine Providence, Rhode Island Transplant Infections: Therapy & Prophylaxis viii Antibiotic Essentials Pierce Gardner, MD Senior Advisor, Clinical Research and Training National Institutes of Health John E. Fogarty International Center for Advanced Study in the Health Sciences Bethesda, Maryland Prophylaxis and Immunization Arthur Gran, MD Infectious Disease Division Winthrop-University Hospital Mineola, New York State University of New York School of Medicine Stony Brook, New York Antimicrobial Drug Summaries Jean E. Hage, MD Infectious Disease Division Winthrop-University Hospital Mineola, New York State University of New York School of Medicine Stony Brook, New York Empiric Therapy of Clinical Syndromes; Prophylaxis & Immunization; Parasitic & Fungi; Unusual Organisms; Antimicrobial Drug Summaries Mark H. Kaplan, MD Professor of Medicine Infectious Diseases University of Michigan School of Medicine Ann Arbor, Michigan HIV Drug Summaries Douglas S. Katz, MD Vice Chairman, Clinical Research and Education Director, Body CT Winthrop-University Hospital Mineola, New York Professor of Clinical Radiology State University of New York School of ­ edicine M Stony Brook, New York Chest X-ray Atlas Raymond S. Koff, MD Clinical Professor of Medicine University of Connecticut School of Medicine Farmington, Connecticut Viral Hepatitis: Therapy & Prophylaxis Leonard R. Krilov, MD Chief, Pediatric Infectious Disease Division Winthrop-University Hospital Mineola, New York Professor of Pediatrics State University of New York School of Medicine Stony Brook, New York Pediatric Infectious Diseases David W. Kubiak, PharmD Infectious Disease Clinical Pharmacist Brigham and Women’s Hospital Boston, Massachusetts Antiretroviral Drug Summaries Brian R Malone, BS, MS, RPh Director, Pharmaceutical Services Winthrop-University Hospital Mineola, New York Adjunct Affiliate Professor College of Pharmacy St. John’s University Queens, New York Pediatric Drug Summaries George H. McCracken, Jr., MD Distinguished Professor of Pediatric Infectious Disease and the Sarah M. and Charles E. Seay Chair in Pediatric Infectious Disease University of Texas Southwestern Medical Center Dallas, Texas Pediatric Infectious Diseases James H. McGuire, MD Master Clinician Division of Infectious Diseases Brigham and Women’s Hospital Professor of Medicine Harvard Medical School Boston, Massachusetts Parasites, Fungi, Unusual Organisms Nardeen Mickail, MD Infectious Disease Division Winthrop-University Hospital Mineola, New York State University of New York School of Medicine, Stony Brook, New York Antimicrobial Drug Summaries Contributors ix Maria D. Mileno, MD Michael F. Rein, MD Director, Travel Medicine The Miriam Hospital Infectious Disease Division Associate Professor of Medicine Brown University Alpert School of Medicine Providence, Rhode Island Prophylaxis and Immunizations Professor of Medicine (Emeritus) University of Virginia Health System Charlottesville, Virginia Sexually Transmitted Diseases Robert Moore, MD Chairman, Department of Radiology Stony Brook University Hospital Professor of Radiology State University of New York School of Medicine Stony Brook, New York Chest X-ray Atlas Sigridh Muñoz-Gomez, MD John H. Rex, MD Adjunct Professor of Medicine University of Texas Medical School Houston, Texas Vice-President Medical Director for Infection AstraZeneca Pharmaceuticals Macclesfield, UK Antifungal Therapy Paul E. Sax, MD Infectious Disease Division Winthrop-University Hospital Mineola, New York State University of New York School of Medicine Stony Brook, New York Antimicrobial Drug Summaries Clinical Director Division of Infectious Diseases and HIV Division of Infectious Diseases Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical School Boston, Massachusetts HIV Infection Ronald L. Nichols, MD David Schlossberg, MD William Henderson Professor of Surgery Professor of Microbiology and Immunology Tulane University School of Medicine New Orleans, Louisiana Surgical Prophylaxis and Therapy Genovefa Papanicolaou, MD Attending Physician, Infectious Disease Service Memorial Sloan Kettering Cancer Center Associate Professor of Medicine Weill Cornell Medical College New York, New York Transplant Infections: Therapy & Prophylaxis Muhammed Raza, MBBS Infectious Disease Division Winthrop-University Hospital Mineola, New York State University of New York School of Medicine Stony Brook, New York Antimicrobial Drug Summaries Tuberculosis Control Program Philadelphia Department of Health Professor of Medicine Temple University School of Medicine Philadelphia, Pennsylvania Tuberculosis Paul E. Schoch, PhD Director Clinical Microbiology Laboratory Winthrop-University Hospital Mineola, New York Medical Microbiology and Gram Stains Atlas Daniel S. Siegal, MD Department of Radiology Mount Auburn Hospital Harvard Medical School Boston, Massachusetts Chest X-ray Atlas x Antibiotic Essentials Stephanie Strollo, MD Infectious Disease Division Winthrop-University Hospital Mineola, New York State University of New York School of Medicine Stony Brook, New York Initial Therapy of Isolates Pending Susceptibility Testing Uzma Syed, DO Infectious Disease Division Winthrop-University Hospital Mineola, New York State University of New York School of Medicine Stony Brook, New York Initial Therapy of Isolates Pending Susceptibility Testing Damary C. Torres, PharmD Clinical Pharmacy Specialist Winthrop-University Hospital Mineola, New York Associate Clinical Professor College of Pharmacy St. John’s University Queens, New York Antimicrobial Drug Summaries Kenneth F. Wagner, DO Infectious Disease Consultant National Naval Medical Center Associate Professor of Medicine Uniformed Services, University of the Health Sciences F. Edward Hebert School of Medicine Bethesda, Maryland Parasites, Fungi, Unusual Organisms xi ACKNOWLEDGMENTS I would like to thank the many contributors who graciously contributed their time and energy; and especially Mark Freed, MD, past President and Editor-in-Chief of Physicians’ Press, for his vision, commitment, and guidance. Burke A. Cunha, MD NOTICE The clinical recommendations set forth in this book are those of the authors and are offered as general guidelines, not specific instructions for individual patients. Clinical judgement should always guide the physician in the selection, dosing, and duration of antimicrobial therapy for individual patients. Not all recommendations in this book are approved indications by the U.S. Food and Drug Administration, and antimicrobial recommendations are not limited to indications in the package insert. The use of any drug should be preceded by careful review of the package insert, which provides indications and dosing approved by the U.S. Food and Drug Administration. The information provided in this book is essential not exhaustive, and the reader is referred to other medical references and the manufacturer’s product literature for further information. Clinical use of the information provided and any consequences that may arise from its use is the responsibility of the prescribing physician. The authors, editors, and publisher do not warrant or guarantee the information herein contained and do not assume and expressly disclaim any liability for errors or omissions or any consequences that may occur from use of this information. BASIS OF RECOMMENDATIONS The therapeutic recommendations in Antibiotic Essentials are based on the contributors’ clinical expertise and experience as well as the literature and clinical guidelines. xii Antibiotic Essentials ABBREVIATIONS ABE ABM ADA AFB AIH AIHA AML ANA ARDS AG A-V β-lactams BAL BG BMT BPH CAB CABG CAC CAH CA-MRSA CAP CD4 CE CFS CGD CIE CLL CML CMV CNS CO-MRSA CoNS CPH CPK CrCl CRE CSD CSF CT CVA CVC CVID CVVH CXR DFA acute bacterial endocarditis acute bacterial meningitis adenosine deaminase acid fast bacilli autoimmune lupoid hepatitis autoimmune hemolytic anemia acute myelogenous leukemia antinuclear antibody adult respiratory distress syndrome Aspergillus galactomannan atrio-ventricular penicillins, cephalosporins, cephamycins (not monobactams or carbapenems) bronchoalveolar lavage b 1, 3 D-glucan bone marrow transplant benign prostatic hypertrophy catheter associated bacteriuria coronary artery bypass grafting catheter associated candiduria chronic active hepatitis community-acquired MRSA community-acquired pneumonia CD4 T-cell lymphocyte California encephalitis virus chronic fatigue syndrome chronic granulomatous disease counter-immunoelectrophoresis chronic lymphocytic leukemia chronic myelogenous leukemia Cytomegalovirus central nervous system community onset MRSA coagulase negative staphylococci chronic persistent hepatitis creatine phosphokinase creatinine clearance carbapenemase resistant Enterobacteriaceae cat scratch disease cerebrospinal fluid computerized tomography costovertebral angle central venous catheter common variable immune deficiency continuous veno venous hemo filtration chest x-ray direct fluorescent antibody DI diabetes insipidus DIC disseminated intravascular coagulation DM diabetes mellitus DOT directly observed therapy e.g. for example EBV Ebstein-Barr virus EEE Eastern equine encephalitis EEG electroencephalogram EIA enzyme immunoassay ELISA enzyme-linked immunosorbent assay EM erythema migrans EMB ethambutol Enterobacteriaceae: Citrobacter, Edwardsiella, Enterobacter, E. coli, Klebsiella, ­­Proteus, Providencia, Shigella, S ­ almonella, Serratia, Hafnia, ­Morganella, Yersinia ESBLs extended spectrum β-lactamases esp especially ESR erythrocyte sedimentation rate ESRD end-stage renal disease ET endotracheal EV enterovirus EVD external ventricular drain FTA-ABS fluorescent treponemal antibody absorption test FUO fever of unknown origin G6PD glucose-6-phosphate dehydrogenase GC gonococcus/gonorrhea GCA giant cell arteritis GI gastrointestinal gm gram GU genitourinary GVHD graft versus host disease HA-MRSA hospital acquired MRSA HAP hospital acquired pneumonia HAV hepatitis A virus HBcAb hepatitis B core antibody HBoV human bocavirus HBsAg hepatitis B surface antigen HBV hepatitis B virus HCV hepatitis C virus HD hemodialysis HDV hepatitis D virus HEV hepatitis E virus HFHD high flux hemodialysis HFV hepatitis F virus HFM hand foot mouth disease HGA HHV-6,7,8 HME hMPV HPS HPV HTLV-1 HRIG HSV I&D IFA IgA IgG IgM IM INH IP IT ITP IV IV/PO IVDA IVIG JE kg L LCM LDH LFTs LGV MAI MCD mcg mcL MDR MDRSP MERS mg mL MIC min MMR MPD MRI MRSA MRSE MS MSSA MSSE MTT MU MVP NDM NHAP Abbreviations xiii human granulocytic anaplasmosis human herpes virus 6,7,8 human monocytic ehrlichiosis human metapneumovirus Hanta virus pulmonary syndrome human papilloma virus human T-cell leukemia virus human rabies immune globulin herpes simplex virus incision and drainage immunofluorescent antibody immunoglobulin A immunoglobulin G immunoglobulin M intramuscular isoniazid intraperitoneal intrathecal idiopathic thrombocytopenic purpura intravenous IV or PO intravenous drug abuser intravenous immunoglobulin Japanese encephalitis kilogram liter lymphocytic choriomeningitis lactate dehydrogenase liver function tests lymphogranuloma venereum Mycobacterium avium-intracellulare multicentric Castleman’s disease microgram microliter multidrug resistant multidrug resistant S. pneumoniae middle east respiratory syndrome milligram milliliter minimum inhibitory concentration minute measles, mumps, rubella myeloprolifevative disorder magnetic resonance imaging methicillin-resistant S. aureus methicillin-resistant S. epidermidis multiple sclerosis methicillin-sensitive S. aureus methicillin-sensitive S. epidermidis methlytetrathiazole million units mitral valve prolapse New Delhi metallo-b-lactamase nursing home acquired pneumonia NNRTI non-nucleoside reverse transcriptase inhibitor nosocomial pneumonia nucleoside reverse transcriptase inhibitor NSAIDs nonsteroidal anti-inflammatory drugs OI opportunistic infection OPAT outpatient parenteral antibiotic therapy PAN polyarteritis nodosa PBC primary biliary cirrhosis PBS protected brush specimen PCEC purified chick embryo cells PCN penicillin PCP Pneumocystis (carinii) jiroveci pneumonia PCR polymerase chain reaction PD peritoneal dialysis PDA patent ductus arteriosus PE Powassan encephalitis PEP post-exposure prophylaxis PI protease inhibitor PID pelvic inflammatory disease progressive multifocal leukoencephalopathy PML PMN polymorphonuclear leucocytes PO oral PPD tuberculin skin test PPIs proton pump inhibitors PPNG penicillinase-producing N. gonorrhoeae PTBM partially treated bacterial meningitis PVE prosthetic valve endocarditis PVL Panton-Valentine leukocidin PZA pyrazinamide q__d every __ days q__h every __ hours q month once a month q week once a week RA rheumatoid arthritis RBC red blood cells RE regional ileitis (Crohn’s disease) RMSF rocky mountain spotted fever RSV respiratory syncytial virus RUQ right upper quadrant RVA rabies vaccine absorbed SARS severe acute respiratory syndrome SBE subacute bacterial endocarditis SCID severe combined immune deficiency SGOT/SGPT serum transaminases SLE systemic lupus erythematosus St. LE Saint Louis encephalitis SOT solid organ transplant sp. species SPB spontaneous bacterial peritonitis SPEP serum protein electrophoresis SQ subcutaneous STD sexually transmitted diseases TA temporal arteritis TAA teichoic acid antibody titers NP NRTI xiv TAH/BSO TB TDF TEE TEN TID TMP TMP–SMX TPN TRNG TSS TTE TTP TURP UC UTI Antibiotic Essentials total abdominal hysterectomy/bilateral salpingoophorectomy M. tuberculosis tenofovir disoproxil fumarate transesophageal echocardiogram toxic epidermal necrolysis three times per day trimethoprim trimethoprim-sulfamethoxazole total parenteral nutrition tetracycline-resistant N.gonorrhoeae toxic shock syndrome transthoracic echocardiogram thrombotic thrombocytopenic purpura transurethral resection of prostate ulcerative colitis urinary tract infection VA VAP VCA VEE VISA VLM VP VRE VRSA VSE VZV WBC WEE WNE XMRV yrs ventriculoatrial ventilator associated pneumonia viral capsid antigen Venezuelan equine encephalitis virus vancomycin intermediate S. aureus visceral larval migrans ventriculoperitoneal vancomycin resistant enterococci vancomycin resistant S. aureus vancomycin-sensitive enterococci varicella zoster virus white blood cells western equine encephalitis west nile encephalitis xenotropic murine leukemia related virus years Chapter 1.  Overview of Antimicrobial Therapy 1 Chapter 1 Overview of Antimicrobial Therapy Burke A. Cunha, MD Cheston B. Cunha, MD Factors in Antibiotic Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Spectrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Tissue Penetration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Antibiotic Resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Factors in Antibiotic Dosing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Dosing in Renal/Hepatic Insufficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Routes of Elimination (Renal and Hepatic) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Microbiology and Susceptibility Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 In Vitro vs. In Vivo Susceptibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Susceptibility Breakpoints for S. pneumoniae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 PK/PD and Other Considerations in Antimicrobial Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Bactericidal vs. Bacteriostatic Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Monotherapy vs. Combination Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 IV to PO Switch Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Bioavailability of Oral Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 OPAT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Duration of Antibiotic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Empiric vs. Specific Antibiotic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Positive Blood Cultures vs. Bacteremia (MSSA, MRSA, CoNS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Drug Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Relative Bradycardia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Antibiotic Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Pitfalls in Antibiotic Prescribing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 References and Suggested Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 2 Antibiotic Essentials Overview of Antimicrobial Therapy FACTORS IN ANTIBIOTIC SELECTION A. Spectrum.  Antibiotic spectrum refers to the range of microorganisms an antibiotic is usually effective against, and is the basis for empiric antibiotic therapy (Chapter 2). Antibiotic susceptibilities are a guide to predicting antibotic effectiveness in blood/well vascularized organs. In vitro testing does not always predict in vivo effectiveness (see p. 6). B. Tissue Penetration.  Antibiotics that are effective against a microorganism in vitro but unable to reach the site of infection are of little or no benefit to the host. Antibiotic tissue penetration depends on properties of the antibiotic, e.g., lipid solubility, molecular size and tissue, e.g., adequacy of blood supply, presence of inflammation. Antibiotic tissue penetration is rarely problematic in acute infections due to increased microvascular permeability from local release of chemical inflammatory mediators. In contrast, chronic infections, e.g., chronic pyelonephritis, chronic prostatitis, chronic osteomyelitis and infections caused by intracellular pathogens often rely on chemical properties of an antibiotic, e.g., high lipid solubility, small molecular size for adequate tissue penetration. Antibiotics cannot be expected to eradicate organisms from areas that are difficult to penetrate or have impaired blood supply, such as abscesses, which usually require surgical drainage for cure. In addition, implanted foreign materials associated with infection usually need to be removed for cure, since microbes causing infections associated with prosthetic joints, shunts, and intravenous lines produce a slime/biofilm on plastic/metal surfaces that permits organisms to survive despite antimicrobial therapy. C. Antibiotic Resistance.  Bacterial resistance to antimicrobial therapy may be classified as natural/intrinsic or acquired relative or absolute. Pathogens not covered by the usual spectrum of an antibiotic are termed naturally/intrinsically resistant, e.g., 25% of S. pneumoniae are naturally resistant to macrolides; acquired resistance refers to a previously susceptible pathogen that is no longer susceptible to an antibiotic, e.g., ampicillin resistant H. influenzae. Organisms with intermediate level (relative) resistance manifests as an increase in minimum inhibitory concentrations (MICs), but are susceptible if achievable serum/tissue concentrations >  MIC, e.g., penicillin-resistant S.  pneumoniae. In contrast, organisms with high level (absolute) resistance manifests as a sudden increase in MICs during therapy, and cannot be overcome by higher-than-usual a ­ ntibiotic doses, e.g., gentamicin-resistant P. aeruginosa. Most acquired antibiotic resistance is agent-specific, not a class specific, and is usually limited to one or two species. Resistance is not related, per se, to volume or duration of use. Some antibiotics have little resistance potential i.e., “low resistance” potential even when used in high volume; other antibiotics can induce resistance, e.g., “high resistance” potential with little use.   The Antibiotic Resistance Potential of each antibiotic is included in each Drug Summary (see Chapter 11). Chapter 1.  Overview of Antimicrobial Therapy 3 Table 1.1. Resistance Potential of Selected Antibiotics Usual Organism(s) Resistant for Each Antibiotic Preferred “Low Resistance Potential” Antibiotic Alternatives in Same Class Preferred “Low Resistance Potential Antibiotic Alternatives in Different Classes P. aeruginosa Amikacin Levofloxacin or Colistin or Cefepime P. aeruginosa Cefepime Levofloxacin or Colistin S. pneumoniae S. aureus Doxycycline or Minocycline Levofloxacin or Moxifloxacin Quinolones  Ciprofloxacin S. pneumoniae Levofloxacin or Moxifloxacin Doxycycline  Ciprofloxicin P. aeruginosa Levofloxican Amikacin or Colistin or Cefepime MSSA MRSA None Linezolid or Daptomycin or Minocycline or Tigecycline P. aeruginosa Meropenem   or Doripenem Amikacin or Cefepime or Colistin “High Resistance Potential” Antibiotics Aminoglycosides  Gentamicin  or  Tobramycin Cephalosporins  Ceftazidime Tetracyclines  Tetracycline Glycopeptides  Vancomycin Carbapenems  Imipenem 4 Antibiotic Essentials Table 1.1. Resistance Potential of Selected Antibiotics (Cont’d) “High Resistance Potential” Antibiotics Usual Organism(s) Resistant for Each Antibiotic Preferred “Low Resistance Potential” Antibiotic Alternatives in Same Class Preferred “Low Resistance Potential Antibiotic Alternatives in Different Classes S. pneumoniae None Doxycycline or Levofloxacin or Moxifloxacin S. pneumoniae None Doxycycline or Levofloxacin or Moxifloxacin Macrolides  Azithromycin Dihydrofolate Reductase Inhibitors  TMP-SMX Adapted from: Cunha BA. Antibiotic Resistance: Effective Control Strategies. Lancet 357:1307-1308, 2001; Cunha BA (Ed). Antibiotic Essentials (12th ed) Jones & Bartlett. Sudbury, MA 2013. p. 521-719 D. Safety Profile.  Whenever possible, avoid antibiotics with serious/frequent side effects. E. Cost.  Switching early from IV to PO antibiotics is the single most important cost saving strategy in hospitalized patients, as the institutional cost of IV administration (~$10/dose) may exceed the cost of the antibiotic itself. Antibiotic costs can also be minimized by using antibiotics with long half-lives, and by choosing monotherapy over combination therapy. FACTORS IN ANTIBIOTIC DOSING A. Renal Insufficiency.  Since most antibiotics eliminated by the kidneys have a wide “toxicto-therapeutic ratio,” dosing strategies are frequently based on formula-derived esti­ ates of m creatinine clearance, rather than precise quantitation of glomerular filtration rates. Dosage adjustments are especially important for antibiotics with narrow toxic-to-therapeutic ratios, and for patients who are receiving other nephrotoxic medications or have preexisting renal disease. Chapter 1.  Overview of Antimicrobial Therapy 5 1. Initial and Maintenance Dosing in Renal Insufficiency.  For drugs eliminated by the kidneys, the initial dose is unchanged, and the maintenance dose/dosing interval are modified in proportion to the degree of renal insufficiency (CrCl). Dosing adjustment problems in renal insufficiency can be circumvented by selecting an antibiotic with a similar spectrum that is eliminated by the hepatic route. 2. Aminoglycoside Dosing. Single daily dosing—adjusted for the degree of renal insufficiency after the loading dose is administered–has virtually eliminated the nephrotoxic potential of aminoglycosides, and is recommended for all patients, including the critically ill (a possible exception is enterococcal endocarditis, where gentamicin dosing every 8 hours may be preferable). Aminoglycoside-induced tubular dysfunction is best assessed by quantitative renal tubular cast counts in urine, which more accurately reflect aminoglycoside nephrotoxicity than serum creatinine. Table 1.2. Dosing Strategies in Hepatic/Renal Insufficiency* Hepatic Insufficiency • Decrease total daily dose of hepatically-eliminated antibiotic by 50% in presence of clinically severe liver disease. • Alternative: Use antibiotic eliminated/inactivated by the renal route in usual dose. Renal Insufficiency (Examples) • If creatinine clearance ~ 40–60 mL/min, decrease dose of renally-eliminated antibiotic by 50% and maintain the usual dosing interval. • If creatinine clearance ~10–40 mL/min, decrease dose of renally-eliminated antibiotic by 50% and double the dosing interval. • Alternative: Use antibiotic eliminated/inactivated by the hepatic route in usual dose. Major Route of Elimination Hepatobiliary Renal Chloramphenicol Pyrazinamide Most b-lactams Amantadine Cefoperazone Linezolid Rimantadine Ceftriaxone† Tedizolid b-lactam/b-lactamase inhibitors Doxycycline Itraconazole Aminoglycosides Valacyclovir Minocycline Isavuconazole TMP–SMX Famciclovir Telithromycin Caspofungin Azthreonam Valganciclovir Moxifloxacin Micafungin Carbapenems Oseltamavir Macrolides Anidulafungin Polymyxin B Zanamavir Nafcillin Ketoconazole Colistin Peramavir Clindamycin Voriconazole Ciprofloxacin Tetracycline Metronidazole Posaconazole Levofloxacin Oxacillin Gatifloxacin Daptomycin Tigecycline Acyclovir