N 1. Choosing Among Antibiotics Within a Class: Beta-lactams, Macrolides, Aminoglycosides, and Fluoroquinolones 2 0 1 2. Choosing Among Antifungal Agents: Polyenes, Azoles, and Echinocandins 5 N N N e ls N N F 3. How Antibiotic Dosages Are Determined Using Susceptibility Data, Pharmacodynamics, and Treatment Outcomes on OH ’s P 4. Community-Associated Methicillin-Resistant Staphylococcus aureus ed iat 2015 r 5. Antimicrobial Therapy for Newborns ic A F CH3 n F 6. Antimicrobial Therapy According to Clinical Syndromes tim Nelson’s Pediatric ic r 7. Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens o b ia Antimicrobial Therapy 8. Preferred Therapy for Specific Fungal Pathogens l T h e ra 21st Edition 9. Preferred Therapy for Specific Viral Pathogens py John S. Bradley, MD 10. Preferred Therapy for Specific Parasitic Pathogens 2 EJodihtonr inD C. hNieef lson, MD 11. Alphabetic Listing of Antimicrobials 1 s t Emeritus E d 12. Antibiotic Therapy for Obese Children it io n Joseph B. Cantey, MD 1134.. SAenqtiumeinctrioabl iPaal rPernotpehryalla-Oxirsa/lP Arenvtiebniotitoicn T ohfe Sryampyp t(Oomraal Stitce Ipn-fdeocwtionn Therapy) for Serious Infections B DJoahvnid A W.D.. KLiemabkee,r lMinD, ,M MDPH r ad Paul E. Palumbo, MD 15. Adverse Reactions to Antimicrobial Agents le y Jason Sauberan, PharmD / N 16. Drug Interactions e William J. Steinbach, MD ls o Contributing Editors n Appendix: Nomogram for Determining Body Surface Area References Index AAP Nelson 2015 COVER SPREAD.indd 1 12/19/14 3:41 PM N N N N N F OH 2015 F CH 3 F Nelson’s Pediatric Antimicrobial Therapy 21st Edition John S. Bradley, MD Editor in Chief John D. Nelson, MD Emeritus Joseph B. Cantey, MD David W. Kimberlin, MD John A.D. Leake, MD, MPH Paul E. Palumbo, MD Jason Sauberan, PharmD William J. Steinbach, MD Contributing Editors NELSON 2015.indb 1 12/19/14 3:39 PM American Academy of Pediatrics Departments of Publishing and Marketing and Sales Staff Mark Grimes, Director, Department of Publishing Alain Park, Senior Product Development Editor Carrie Peters, Editorial Assistant Sandi King, MS, Director, Division of Editorial and Production Services Shannan Martin, Publishing and Production Services Specialist Linda Diamond, Manager, Art Direction and Production Jason Crase, Manager, Editorial Services Houston Adams, Digital Content and Production Specialist Mary Lou White, Director, Department of Marketing and Sales Linda Smessaert, MSIMC, Brand Manager, Clinical and Professional Publications Published by the American Academy of Pediatrics 141 Northwest Point Blvd, Elk Grove Village, IL 60007-1019 847/434-4000 Fax: 847/434-8000 www.aap.org ISSN: 2164-9278 (print) ISSN: 2164-9286 (electronic) ISBN: 978-1-58110-918-4 eBook: 978-1-58110-917-7 MA0746 The recommendations in this publication do not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. This book has been developed by the American Academy of Pediatrics. The authors, editors, and contributors are expert authorities in the field of pediatrics. No commercial involvement of any kind has been solicited or accepted in the development of the content of this publication. Every effort has been made to ensure that the drug selection and dosages set forth in this text are in accordance with the current recommendations and practice at the time of the publication. It is the responsibility of the health care professional to check the package insert of each drug for any change in indications or dosage and for added warnings and precautions. Brand names are furnished for identifying purposes only. No endorsement of the manufacturers or products listed is implied. Please see our Web site for content-related notices and updates: www.aap.org/nelsonsabx. Copyright © 2015 John S. Bradley and John D. Nelson Publishing rights, American Academy of Pediatrics. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior permission from the authors. First edition published in 1975. 9-360 1 2 3 4 5 6 7 8 9 10 NELSON 2015.indb 2 12/19/14 3:39 PM iii Editor in Chief Emeritus John S. Bradley, MD John D. Nelson, MD Professor of Pediatrics Professor Emeritus of Pediatrics Chief, Division of Infectious Diseases, The University of Texas Department of Pediatrics Southwestern Medical Center at Dallas University of California, San Diego, Southwestern Medical School School of Medicine Dallas, TX Director, Division of Infectious Diseases, Rady Children’s Hospital San Diego San Diego, CA Contributing Editors Joseph B. Cantey, MD Paul E. Palumbo, MD Assistant Professor of Pediatrics Professor of Pediatrics and Medicine Divisions of Neonatology and Infectious Geisel School of Medicine at Dartmouth Diseases, Department of Pediatrics Director, International Pediatric HIV Program UT Southwestern Dartmouth-Hitchcock Medical Center Dallas, TX Lebanon, NH David W. Kimberlin, MD Jason Sauberan, PharmD Professor of Pediatrics Assistant Clinical Professor Codirector, Division of Pediatric University of California, San Diego, Infectious Diseases Skaggs School of Pharmacy and Sergio Stagno Endowed Chair in Pharmaceutical Sciences Pediatric Infectious Diseases Rady Children’s Hospital San Diego University of Alabama at Birmingham San Diego, CA Birmingham, AL William J. Steinbach, MD John A.D. Leake, MD, MPH Associate Professor of Pediatrics, Professor of Pediatrics Division of Pediatric Infectious Diseases Division of Infectious Diseases, Associate Professor of Molecular Genetics Department of Pediatrics and Microbiology University of California, San Diego, Director, International Pediatric Fungal School of Medicine Network Division of Infectious Diseases, Duke University School of Medicine Rady Children’s Hospital San Diego Durham, NC San Diego, CA NELSON 2015.indb 3 12/19/14 3:39 PM NELSON 2015.indb 4 12/19/14 3:39 PM v Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii 1. Choosing Among Antibiotics Within a Class: Beta-lactams, Macrolides, Aminoglycosides, and Fluoroquinolones ................................................1 2. Choosing Among Antifungal Agents: Polyenes, Azoles, and Echinocandins ......7 3. How Antibiotic Dosages Are Determined Using Susceptibility Data, Pharmacodynamics, and Treatment Outcomes .......................................13 4. Community-Associated Methicillin-Resistant Staphylococcus aureus ............15 5. Antimicrobial Therapy for Newborns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 A. Recommended Therapy for Selected Newborn Conditions .......................20 B. Antimicrobial Dosages for Neonates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 C. Aminoglycosides. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 D. Vancomycin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 E. Use of Antimicrobials During Pregnancy or Breastfeeding .......................40 6. Antimicrobial Therapy According to Clinical Syndromes ............................41 A. Skin and Soft Tissue Infections ........................................................43 B. Skeletal Infections .......................................................................47 C. Eye Infections ............................................................................49 D. Ear and Sinus Infections ................................................................52 E. Oropharyngeal Infections ..............................................................55 F. Lower Respiratory Tract Infections ....................................................58 G. Cardiovascular Infections ..............................................................69 H. Gastrointestinal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 I. Genital and Sexually Transmitted Infections ........................................79 J. Central Nervous System Infections ....................................................83 K. Urinary Tract Infections .................................................................87 L. Miscellaneous Systemic Infections ...................................................88 7. Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens. . . . . . . . . . 95 A. Common Bacterial Pathogens and Usual Pattern of Susceptibility to Antibiotics (Gram Positive) .............................................................96 B. Common Bacterial Pathogens and Usual Pattern of Susceptibility to Antibiotics (Gram Negative) ............................................................98 C. Common Bacterial Pathogens and Usual Pattern of Susceptibility to Antibiotics (Anaerobes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .100 D. Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens ........102 NELSON 2015.indb 5 12/19/14 3:39 PM vi — Contents 8. Preferred Therapy for Specific Fungal Pathogens ...................................117 A. Overview of Fungal Pathogens and Usual Pattern of Susceptibility to Antifungals ...........................................................................118 B. Systemic Infections .....................................................................120 C. Localized Mucocutaneous Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .129 9. Preferred Therapy for Specific Viral Pathogens ......................................131 A. Overview of Non-HIV Viral Pathogens and Usual Pattern of Susceptibility to Antivirals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .132 B. Preferred Therapy for Specific Viral Pathogens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .133 10. Preferred Therapy for Specific Parasitic Pathogens .................................143 11. Alphabetic Listing of Antimicrobials ...................................................157 A. Systemic Antimicrobials With Dosage Forms and Usual Dosages ...............158 B. Topical Antimicrobials (Skin, Eye, Ear) ...............................................175 12. Antibiotic Therapy for Obese Children ................................................183 13. Sequential Parenteral-Oral Antibiotic Therapy (Oral Step-down Therapy) for Serious Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .187 14. Antimicrobial Prophylaxis/Prevention of Symptomatic Infection ...............189 A. Postexposure Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .191 B. Long-term Symptomatic Disease Prophylaxis .....................................197 C. Preemptive Treatment/Latent Infection Treatment (“Prophylaxis of Symptomatic Infection”) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .198 D. Surgical/Procedure Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .198 15. Adverse Reactions to Antimicrobial Agents ..........................................203 16. Drug Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .211 Appendix: Nomogram for Determining Body Surface Area ............................215 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217 Index ..............................................................................................237 NELSON 2015.indb 6 12/19/14 3:39 PM vii Introduction Welcome to the 21st edition: Nelson’s Pediatric Antimicrobial Therapy 2015! Our collaboration with the American Academy of Pediatrics (AAP) has become stronger and more integrated as we work closely with our AAP editor, Alain Park. The book is at a crossroads, trying to decide whether to stay small and concise or to expand and give our contributing editors free rein to make recommendations as well as tell us all why the recommendations are being made. In addition, the AAP has interviewed a number of health care professionals who own this book to provide some valuable advice on which sections should be expanded and which should be deleted, helping us write a more focused set of chapters. Along those lines, we have created some new tables that provide a quick at-a-glance overview of bacterial and fungal pathogen susceptibilities to commonly used antimicrobials. The iPhone/iPad app has been very successful. The Android version of the app (which we have used) was not updated for the 2014 edition of the book, but if we get enough requests for this version of the app in the future, we may develop one for subsequent editions. However, we were very pleased to learn in our survey that many still prefer the book format. The collective advice and experience of the editors is still backed up by grading our recommendations: our assessment of how strongly we feel about a recommendation and the strength of the evidence to support our recommendation (noted below). Strength of Recommendation Description A Strongly recommended B Recommended as a good choice C One option for therapy that is adequate, perhaps among many other adequate therapies Level of Evidence Description I Based on well-designed, prospective, randomized, and controlled studies in an appropriate population of children II Based on data derived from prospectively collected, small comparative trials, or noncomparative prospective trials, or reasonable retrospective data from clinical trials in children, or data from other populations (eg, adults) III Based on case reports, case series, consensus statements, or expert opinion for situations in which sound data do not exist NELSON 2015.indb 7 12/19/14 3:39 PM viii — Introduction For this edition, Joseph B. (JB) Cantey is taking over work on Chapter 5, Antimicrobial Therapy for Newborns, from Pablo Sanchez, whose role on creating the chapter on newborns goes back decades. We wish Pablo the best of luck in his new position in Columbus, OH. JB follows in Pablo’s footsteps with expertise as a double-trained infectious diseases/neonatologist. Jason Sauberan continues to carefully update the Antimicrobial Dosages for Neonates with the tremendous amount of new information becoming available. The neonatal pharmacology field gets ever more complicated with new drugs and our increasing understanding of organ system maturation and drug dis- tribution. We are very happy to have John van den Anker, a neonatologist/pharmacologist from Children’s National Medical Center, working with us again this year on the neonatal dosage table; he is personally responsible for much of the new information we have on neonatal developmental pharmacology. We are extremely fortunate to have as editors some of the best clinicians in pediatric infectious diseases out there. They take the time to partner with the AAP and provide amazing advice and insight in their particular areas of interest, knowledge, and experience. David Kimberlin, John Leake, Jason Sauberan, and Bill Steinbach are each exceptionally talented and collaborative! As we state each year, many of the recommendations by the editors for specific situations have not been systematically evaluated in controlled, prospective, comparative clinical trials. Many of the recommendations may be supported by published data, but for many possible reasons, the data have never been presented to or reviewed by the US Food and Drug Administration (FDA) and therefore are not in the package label. We in pediatrics find ourselves in this situation frequently. Many of us are working closely with the FDA to try to narrow the gap in our knowledge of antimicrobial agents between adults and children. We are deeply grateful for the hard work and tireless efforts of Alain Park, our AAP senior product development editor, who challenges us to come up with new ways to share our information with pediatric health care professionals. How about an AAP Nelson’s Editors’ Infectious Diseases Update continuing medical education program? We have wonderful supporters in the AAP Departments of Marketing and Publications— Jeff Mahony, Mark Grimes, Linda Smessaert, and Maureen DeRosa—who make certain that all our recommendations make it to everyone as effectively and effortlessly as possible. John S. Bradley, MD, FAAP John D. Nelson, MD NELSON 2015.indb 8 12/19/14 3:39 PM 2015 Nelson’s Pediatric Antimicrobial Therapy — 1 1. Choosing Among Antibiotics Within a Class: Beta-lactams, 1 Macrolides, Aminoglycosides, and Fluoroquinolones New drugs should be compared with others in the same class regarding (1) antimicro- ones ol bial spectrum; (2) degree of antibiotic exposure (a function of the pharmacokinetics of uin the nonprotein-bound drug at the site of infection and the pharmacodynamic prop- oq or etrritaielss; o(f4 )th teo lderruang)c;e (,3 t)o dxiecmitoy,n asntrda tseidd ee ffieffceacctys ;i nan add e(q5u) actoes at.n Idf twheelrl-ec iosn ntoro slulebds tcalinntiicaal l nd Flu benefit for efficacy or safety, one should opt for using an older, more familiar, and less des, a expensive drug with the narrowest spectrum of activity required to treat the infection. osi Beta-lactams oglyc n Oral Cephalosporins (cephalexin, cefadroxil, cefaclor, cefprozil, cefuroxime, cefixime, Ami cefdinir, cefpodoxime, cefditoren [tablet only], and ceftibuten). As a class, the oral des, cephalosporins have the advantages over oral penicillins of somewhat greater safety oli and greater palatability of the suspension formulations (penicillins have a bitter taste). Macr The serum half-lives of cefpodoxime, ceftibuten, and cefixime are greater than 2 hours. ms, Thdflceuofsiiudser s poh phxaeailmfrr- mldeif,aa eycc e iofsfok dlriiin knceeeitrlryi,t c cat efoienfi ab xitenium dmreiecu ,aa cccthecio folpnouosnn,dg tpose axrfr oittmrhi cateuhn, lea at nrhfaldeyc csto eettrfthituaiibmst umt htheeeandyl f ih-mala,i afvweye.h btCeheree egf aaitvcdhleveona rm n,i nctiaed 1gfdp eolr eoro- vez2eia l rr, Class: Beta-lacta cephalexin and cefadroxil (the “first-generation cephalosporins”) of enhanced coverage n a hi for Haemophilus influenzae (including beta-lactamase–producing strains) and some Wit ednistaedrivca gnrtaamge- onfe gleastsi vaec tbiavcitiyll ia; ghaoinwsetv Setrr,e cpetftociboucctuens pannedu cmeofinxiiamee t hina np athrtei coutlhaerr hs,a pvae rt-h e biotics ticularly against penicillin (beta-lactam) non-susceptible strains. None of the currently Anti g available oral cephalosporins have activity against Pseudomonas or methicillin-resistant n o m Staphylococcus aureus (MRSA). The palatability of generic versions of these products A g may not have the same pleasant characteristics as the original products. osin o Parenteral Cephalosporins. First-generation cephalosporins, such as cefazolin, are Ch used mainly for treatment of gram-positive infections (excluding MRSA) and for surgical prophylaxis; the gram-negative spectrum is limited. Cefazolin is well tolerated on intramuscular or intravenous injection. A second-generation cephalosporin (cefuroxime) and the cephamycins (cefoxitin and cefotetan) provide increased activity against many gram-negative organisms, particularly Haemophilus and Escherichia coli. Cefoxitin has, in addition, activity against approxi- mately 80% of strains of Bacteroides fragilis and can be considered for use in place of metronidazole, clindamycin, or carbapenems when that organism is implicated in non–life-threatening disease. Third-generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime) all have enhanced potency against many enteric gram-negative bacilli. They are inactive against enterococci and Listeria and only ceftazidime has significant activity against Pseudomonas. Cefotaxime and ceftriaxone have been used very successfully to treat NELSON 2015.indb 1 12/19/14 3:39 PM