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Part 1 book “Nelson’s pediatric antimicrobial therapy” has contents: Choosing among antibiotics within a class; choosing among antifungal agents - polyenes, azoles, and echinocandins; approach to antibiotic therapy of drug-resistant gram-negative bacilli and methicillin-resistant staphylococcus aureus,… and other contents.

HO Choosing Among Antifungal Agents: Polyenes, Azoles, and Echinocandins How Antibiotic Dosages Are Determined Using Susceptibility Data, Pharmacodynamics, and Treatment Outcomes Approach to Antibiotic Therapy of Drug-Resistant Gram-negative Bacilli and Methicillin-Resistant ­Staphylococcus ­aureus Antimicrobial Therapy for Newborns Antimicrobial Therapy According to Clinical Syndromes Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens Preferred Therapy for Specific Fungal Pathogens Preferred Therapy for Specific Viral Pathogens 10 Preferred Therapy for Specific Parasitic Pathogens 11 Alphabetic Listing of Antimicrobials 2018 Nelson’s Pediatric Antimicrobial Therapy Choosing Among Antibiotics Within a Class: Beta-lactams, Macrolides, Aminoglycosides, and Fluoroquinolones OH O O HO H OH HN HN O 2018 NH2 NH Nelson’s Pediatric Antimicrobial Therapy John S Bradley, MD 24th Edition Editor in Chief John D Nelson, MD Emeritus 24th Edition 12 Antibiotic Therapy for Children Who Are Obese 13 Sequential Parenteral-Oral Antibiotic Therapy (Oral Step-down Therapy) for Serious Infections 14 Antimicrobial Prophylaxis/Prevention of Symptomatic Infection Bradley Nelson 15 Adverse Reactions to Antimicrobial Agents Appendix: Nomogram for Determining Body Surface Area Elizabeth D Barnett, MD Joseph B Cantey, MD David W Kimberlin, MD Paul E Palumbo, MD Jason Sauberan, PharmD William J Steinbach, MD Contributing Editors References ISBN 978-1-61002-109-8 Index 90000> 781610 021098 AAP mebooksfree.com NELSON-2018_CoverSpread.indd 11/21/17 1:22 PM 2018 Nelson’s Pediatric Antimicrobial Therapy John S Bradley, MD 24th Edition Editor in Chief John D Nelson, MD Emeritus Elizabeth D Barnett, MD Joseph B Cantey, MD David W Kimberlin, MD Paul E Palumbo, MD Jason Sauberan, PharmD William J Steinbach, MD Contributing Editors mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM American Academy of Pediatrics Publishing Staff Mark Grimes, Director, Department of Publishing Peter Lynch, Manager, Digital Strategy and Product Development Barrett Winston, Senior Editor, Professional and Clinical Publishing Shannan Martin, Production Manager, Consumer Publications Jason Crase, Manager, Editorial Services Mary Lou White, Chief Product and Services Officer/SVP, Membership, Marketing, and Publishing Linda Smessaert, MSIMC, Senior Marketing Manager, Professional Resources Mary Louise Carr, MBA, Marketing Manager, Clinical Publications Published by the American Academy of Pediatrics 345 Park Blvd Itasca, IL 60143 Telephone: 847/434-4000 Facsimile: 847/434-8000 www.aap.org The recommendations in this publication not indicate an exclusive course of treatment or serve as a standard of medical care Variations, taking into account individual circumstances, may be appropriate Statements and opinions expressed are those of the authors and not necessarily those of the American Academy of Pediatrics Web sites are mentioned for informational purposes only and not imply an endorsement by the American Academy of Pediatrics Web site addresses are as current as possible but may change at any time Brand names are furnished for identifying purposes only No endorsement of the manufacturers or products listed is implied This publication has been developed by the American Academy of Pediatrics The authors, e­ ditors, 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 current recommendations and practice at the time of 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 Special discounts are available for bulk purchases of this publication E-mail our Special Sales Department at aapsales@aap.org for more information © 2018 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 Printed in the United States of America 9-393/1217     10 MA0837 ISSN: 2164-9278 (print) ISSN: 2164-9286 (electronic) ISBN: 978-1-61002-109-8 eBook: 978-1-61002-110-4 mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM iii Editor in Chief Emeritus John S Bradley, MD John D Nelson, MD Professor of Pediatrics Chief, Division of Infectious Diseases, Department of Pediatrics University of California, San Diego, School of Medicine Director, Division of Infectious Diseases, Rady Children’s Hospital San Diego San Diego, CA Professor Emeritus of Pediatrics The University of Texas Southwestern Medical Center at Dallas Southwestern Medical School Dallas, TX Contributing Editors Elizabeth D Barnett, MD Professor of Pediatrics Boston University School of Medicine Director, International Clinic and Refugee Health Assessment Program, Boston Medical Center GeoSentinel Surveillance Network, Boston Medical Center Boston, MA Joseph B Cantey, MD Assistant Professor of Pediatrics Divisions of Pediatric Infectious Diseases and Neonatology/Perinatal Medicine University of Texas Health Science Center at San Antonio San Antonio, TX David W Kimberlin, MD Professor of Pediatrics Codirector, Division of Pediatric Infectious Diseases Sergio Stagno Endowed Chair in Pediatric Infectious Diseases University of Alabama at Birmingham Birmingham, AL Paul E Palumbo, MD Professor of Pediatrics and Medicine Geisel School of Medicine at Dartmouth Director, International Pediatric HIV Program Dartmouth-Hitchcock Medical Center Lebanon, NH Jason Sauberan, PharmD Assistant Clinical Professor University of California, San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences Rady Children’s Hospital San Diego San Diego, CA William J Steinbach, MD Professor of Pediatrics Professor in Molecular Genetics and Microbiology Chief, Division of Pediatric Infectious Diseases Director, International Pediatric Fungal Network Duke University School of Medicine Durham, NC mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM v Contents Introduction vii Notable Changes to 2018 Nelson’s Pediatric Antimicrobial Therapy, 24th Edition x Choosing Among Antibiotics Within a Class: Beta-lactams, Macrolides, Aminoglycosides, and Fluoroquinolones Choosing Among Antifungal Agents: Polyenes, Azoles, and Echinocandins How Antibiotic Dosages Are Determined Using Susceptibility Data, Pharmacodynamics, and Treatment Outcomes 17 Approach to Antibiotic Therapy of Drug-Resistant Gram-negative Bacilli and Methicillin-Resistant Staphylococcus aureus 21 Antimicrobial Therapy for Newborns 29 A Recommended Therapy for Selected Newborn Conditions 30 B Antimicrobial Dosages for Neonates 49 C Aminoglycosides 53 D Vancomycin 53 E Use of Antimicrobials During Pregnancy or Breastfeeding 54 Antimicrobial Therapy According to Clinical Syndromes 55 A Skin and Soft Tissue Infections 57 B Skeletal Infections 62 C Eye Infections 65 D Ear and Sinus Infections 69 E Oropharyngeal Infections 72 F Lower Respiratory Tract Infections 75 G Cardiovascular Infections 88 H Gastrointestinal Infections 95 I Genital and Sexually Transmitted Infections 102 J Central Nervous System Infections 106 K Urinary Tract Infections 110 L Miscellaneous Systemic Infections 112 Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens .119 A Common Bacterial Pathogens and Usual Pattern of Susceptibility to Antibiotics (Gram Positive) 120 B Common Bacterial Pathogens and Usual Pattern of Susceptibility to Antibiotics (Gram Negative) 122 C Common Bacterial Pathogens and Usual Pattern of Susceptibility to Antibiotics (Anaerobes) 124 D Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens 126 mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM vi — Contents Preferred Therapy for Specific Fungal Pathogens 143 A Overview of More Common Fungal Pathogens and Their Usual Pattern of Antifungal Susceptibilities 144 B Systemic Infections 146 C Localized Mucocutaneous Infections 159 Preferred Therapy for Specific Viral Pathogens 161 A Overview of Non-HIV Viral Pathogens and Usual Pattern of Susceptibility to Antivirals .162 B Preferred Therapy for Specific Viral Pathogens .164 10 Preferred Therapy for Specific Parasitic Pathogens 177 A Selected Common Pathogenic Parasites and Suggested Agents for Treatment 178 B Preferred Therapy for Specific Parasitic Pathogens .180 11 Alphabetic Listing of Antimicrobials 199 A Systemic Antimicrobials With Dosage Forms and Usual Dosages 201 B Topical Antimicrobials (Skin, Eye, Ear) 221 12 Antibiotic Therapy for Children Who Are Obese 229 13 Sequential Parenteral-Oral Antibiotic Therapy (Oral Step-down Therapy) for Serious Infections .233 14 Antimicrobial Prophylaxis/Prevention of Symptomatic Infection 235 A Postexposure Antimicrobial Prophylaxis to Prevent Infection 237 B Long-term Antimicrobial Prophylaxis to Prevent Symptomatic New Infection .244 C Prophylaxis of Symptomatic Disease in Children Who Have Asymptomatic Infection/Latent Infection 245 D Surgical/Procedure Prophylaxis 246 15 Adverse Reactions to Antimicrobial Agents 251 Appendix: Nomogram for Determining Body Surface Area 259 References .261 Index 285 mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM vii Introduction We are very fortunate to be in our 24th edition of Nelson’s Pediatric Antimicrobial Therapy as we continue to gain momentum in our partnership with the American Academy of Pediatrics (AAP)! Even though it has only been a year since the last revision, there are many important additions, including the approval of a second new antibiotic to treat methicillin-resistant Staphylococcus aureus infections and the significant advances in clinical studies for antibiotics to treat the ever-increasing multidrug-­ resistant gram-negative bacilli that are now in the community (we have a new algorithm to help decide which antibiotic to choose for these pathogens in Chapter 4) All the contributing editors have updated their sections with important new recommendations based on current published data, guidelines, and clinical experience that provide a ­perspective for interpretation of relevant information unsurpassed in the pediatric infectious diseases community We are approaching 400 references to support recommendations in Chapter 6, Antimicrobial Therapy According to Clinical Syndromes, alone Recognizing the talent in collaborators/colleagues of the editors, and their substantial and ongoing contributions to the quality of the material that is presented in this book, we have created consulting editors, whom we wish to continue to acknowledge each year in this Introduction We continue to have the opportunity to receive valuable suggestions from Drs Pablo Sanchez and John van den Anker on antimicrobial therapy of the newborn, in support of the work done by JB Cantey and Jason Sauberan on Chapter For those who use the Nelson’s app, we have a new consulting editor, Dr Howard Smart, to help us create more user-friendly software Howard is the chief of pediatrics at the Sharp-Rees Stealy multispecialty medical group in San Diego, CA; a graduate of our University of California, San Diego (UCSD) pediatric residency with additional training in pulmonology; and a tech wizard Howard writes (and sells) his own apps for the iOS platform and actually took parts of the 2017 edition and created his own version of our app! With the support of the AAP and the editors, we plan to incorporate Howard’s new enhancements in this 2018 edition A second consulting editor this year is also part of the San Diego pediatric community, Dr Brian Williams, who trained in medicine and pediatrics during his UCSD residency and trained in medicine and pediatrics as a hospitalist I often see Brian on the wards of our hospital in his role as a hospitalist, taking care of children with infections (among other things), getting advice from Nelson’s Brian needs a quick and efficient way to access information, and his advice on organizing information (particularly the search mode of the app) has been invaluable He is focused, practical, and very collaborative, having come from Wisconsin You will find many improvements in this 2018 edition based on his suggestions to the AAP and the editors, with many more to come, we hope We continue to harmonize the Nelson’s book with the AAP Red Book, and we were given relevant information from the upcoming 2018 edition (easy to understand, given that David Kimberlin is also the editor of the Red Book) We are virtually always in sync with explanations that allow the reader to understand the basis for recommendations mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM viii — Introduction We continue to provide grading of our recommendations—our assessment of how strongly we feel about a recommendation and the strength of the evidence to support our recommendation (noted in the Table) 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 not exist 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 the data may never have been presented to or reviewed by the US Food and Drug Administration (FDA) and, therefore, are not in the package label We all 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; the FDA pediatric infectious diseases staff is providing an exceptional effort to shed light on the doses that are safe and effective for neonates, infants, and children, with major efforts to place important new data on safety and efficacy in the antibiotic package labels Barrett Winston, our primary AAP editorial contact, has done an amazing job of organizing all the AAP staff, as well as the contributing and consulting editors, to keep us all moving forward with enhancements and upgrades as we now look to the long-term future of the book in partnership with the AAP Peter Lynch has been working on developing Nelson’s online, as well as the app, and has shared considerable AAP resources with us We, of course, continue to appreciate the teamwork of all those at the AAP who make sure this book gets to all the clinicians who may benefit Thanks to Mark Grimes, Director, Department of Publishing, and our steadfast friends and supporters in the mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM Introduction — ix AAP departments of Publishing and Membership Engagement, Marketing, and Sales— Jeff Mahony, Director, Division of Professional and Consumer Publishing; Linda Smessaert, Senior Marketing Manager, Professional Resources; and the entire staff—who make certain that the considerable information in Nelson’s makes it to those who are actually caring for children We are still very interested to learn from readers/users if there are new chapters or ­sections you wish for us to develop—and whether you find certain sections particularly helpful, so we don’t change or delete them! Please send your suggestions to nelsonabx@aap.org We are also incredibly pleased that John Nelson was given an award by the AAP on July 27, 2017, at the AAP PREP:ID course for a lifetime of achievement in education and improving care to children with infectious diseases We will include a picture of the presentation in the 2018 app when Howard figures out how to attach it! John S Bradley, MD Pictured from left: Jason Sauberan, PharmD; John S Bradley, MD; John D Nelson, MD; David W Kimberlin, MD; and William J Steinbach, MD Pictured from left: Mark Grimes; Dr Bradley; Dr Sauberan; Dr Steinbach; Elizabeth D Barnett, MD; Joseph B Cantey, MD; and Barrett Winston mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM x Notable Changes to 2018 Nelson’s Pediatric Antimicrobial Therapy, 24th Edition Antifungals • Addition of Candida auris • Specific recommendations about antifungal therapeutic drug levels • Expanded and new references • Most current antifungal activity spectrum table • New coccidioidomycosis guidelines incorporated • New approaches to mucormycosis included Antimicrobials • Antibiotics that are no longer available: cefditoren (Spectracef), ceftibuten (Cedax), penicillin G procaine • New daptomycin, entecavir, linezolid, and voriconazole dosing • New mebendazole products (Warning: may not yet be commercially available at time of publication) Drug-Resistant Gram-negative Bacilli and Methicillin-Resistant Staphylococcus aureus • New discussion and algorithm for selection of antibiotics for presumed or documented Gram-negative, multidrug-resistant pathogens • Updated tables for susceptibility of Gram-positive and Gram-negative pathogens • Where the newly US Food and Drug Administration–approved pediatric antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) (daptomycin and ceftaroline) fit into treatment strategy with increasing clindamycin resistance References • Updated references and reviews for therapy of clinically important infections (eg, community-acquired pneumonia in children, endocarditis, MRSA infections) • Updated references for antibiotic prophylaxis to prevent infection following exposures; surgical prophylaxis mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 10 11/20/17 9:25 AM mebooksfree.com ch00-Nelson-2018_FM_i-x.indd 11/20/17 9:25 AM ... formulation, as mebooksfree.com ch02-Nelson-2 018 _009- 016 .indd 10 11 / 21/ 17 11 :17 AM 2 018 Nelson’s Pediatric Antimicrobial Therapy — 11 Azoles This class of systemic agents was first approved in 19 81 and... mg on the first day, followed by 10 0 mg daily mebooksfree.com ch02-Nelson-2 018 _009- 016 .indd 16 11 / 21/ 17 11 :17 AM 2 018 Nelson’s Pediatric Antimicrobial Therapy — 17 How Antibiotic Dosages Are Determined... ch03-Nelson-2 018 _ 017 -020.indd 19 11 /13 /17 10 :05 AM mebooksfree.com ch00-Nelson-2 018 _FM_i-x.indd 11 /20 /17 9:25 AM 2 018 Nelson’s Pediatric Antimicrobial Therapy — 21 Approach to Antibiotic Therapy of Drug-Resistant

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