2. Choosing Among Antifungal Agents: Polyenes, Azoles, and Echinocandins
3. How Antibiotic Dosages Are Determined Using Susceptibility Data, Pharmacodynamics, and Treatment Outcomes
4.Approach to Antibiotic Therapy of Drug-Resistant Gram-negative Bacilli and Methicillin-Resistant
­Staphylococcus ­aureus
5. Antimicrobial Therapy for Newborns
6. Antimicrobial Therapy According to Clinical Syndromes
7. Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens
8. Preferred Therapy for Specific Fungal Pathogens
9. Preferred Therapy for Specific Viral Pathogens
10. Preferred Therapy for Specific Parasitic Pathogens
11. Alphabetic Listing of Antimicrobials

13. Sequential Parenteral-Oral Antibiotic Therapy (Oral Step-down Therapy) for Serious Infections
14. Antimicrobial Prophylaxis/Prevention of Symptomatic Infection

References

Bradley
Nelson

Appendix: Nomogram for Determining Body Surface Area

25th Edition

12. Antibiotic Therapy for Children Who Are Obese

2019 Nelson’s Pediatric Antimicrobial Therapy

1. Choosing Among Antibiotics Within a Class: Beta-lactams and Beta-lactamase Inhibitors, Macrolides,
Aminoglycosides, and Fluoroquinolones

2019

Nelson’s Pediatric
Antimicrobial Therapy
John S. Bradley, MD
Editor in Chief

John D. Nelson, MD
Emeritus

25

TH

EDITION

Elizabeth D. Barnett, MD
Joseph B. Cantey, MD
David W. Kimberlin, MD
Paul E. Palumbo, MD
Jason Sauberan, PharmD
J. Howard Smart, MD
William J. Steinbach, MD
Contributing Editors

Index

AAP

NELSON PEDIATRIC SPREAD 2019 FINAL.indd All Pages


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2019

Nelson’s Pediatric
Antimicrobial Therapy
John S. Bradley, MD

25th 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
J. Howard Smart, MD
William J. Steinbach, MD
Contributing Editors

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American Academy of Pediatrics Publishing Staff
Mary Lou White, Chief Product and Services Officer/SVP, Membership, Marketing, and Publishing
Mark Grimes, Vice President, Publishing
Peter Lynch, Senior Manager, Digital Strategy and Product Development
Mary Kelly, Senior Editor, Professional and Clinical Publishing
Shannan Martin, Production Manager, Consumer Publications
Jason Crase, Manager, Editorial Services
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: 630/626-6000
Facsimile: 847/434-8000
www.aap.org
The American Academy of Pediatrics is an organization of 67,000 primary care pediatricians, pediatric medical
subspecialists, and pediatric surgical specialists dedicated to the health, safety, and well-being of infants,
children, adolescents, and young adults.
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.
Statements and opinions expressed are those of the authors and not necessarily those of the
American Academy of Pediatrics.
Products and Web sites are mentioned for informational purposes only and do 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.
The publishers have made every effort to trace the copyright holders for borrowed materials.
If they have inadvertently overlooked any, they will be pleased to make the necessary
arrangements at the first opportunity.

This publication 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. Disclosures: Dr Kimberlin
disclosed a consulting relationship with Slack Incorporated. Dr Palumbo disclosed a safety monitoring
board relationship with Janssen Pharmaceutical Companies. Dr Steinbach disclosed an advisory board
relationship with Merck & Company and Astellas Pharma, Inc.
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, and to review newly published, peer-reviewed data in
the medical literature for current data on safety and efficacy.
Special discounts are available for bulk purchases of this publication.
E-mail Special Sales at for more information.
© 2019 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.
9-422/1218     1 2 3 4 5 6 7 8 9 10
MA0881
ISSN: 2164-9278 (print)
ISSN: 2164-9286 (electronic)
ISBN: 978-1-61002-210-1
eBook: 978-1-61002-226-2

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iii
Editor in Chief

Emeritus

John S. Bradley, 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

John D. Nelson, MD
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
Editor, Red Book: 2018–2021 Report of the
Committee on Infectious Diseases,
31st Edition
Professor of Pediatrics
Codirector, Division of Pediatric
Infectious Diseases
Sergio Stagno Endowed Chair in
Pediatric Infectious Diseases
University of Alabama at Birmingham
Birmingham, AL

ch00-Nelson-2019_FM_i-xii.indd 3

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
J. Howard Smart, MD
Chairman, Department of Pediatrics
Sharp Rees-Stealy Medical Group
Assistant Clinical Professor of Pediatrics
University of California, San Diego
School of Medicine
San Diego, CA
William J. Steinbach, MD
Professor of Pediatrics
Professor in Molecular Genetics
and Microbiology
Chief, Division of Pediatric Infectious Diseases
Director, Duke Pediatric
Immunocompromised Host Program
Director, International Pediatric Fungal
Network
Duke University School of Medicine
Durham, NC

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v

Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Notable Changes to 2019 Nelson’s Pediatric Antimicrobial Therapy,
25th Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
1. Choosing Among Antibiotics Within a Class: Beta-lactams and Beta-lactamase
Inhibitors, Macrolides, Aminoglycosides, and Fluoroquinolones . . . . . . . . . . . . . . . . . . . 1
2. Choosing Among Antifungal Agents: Polyenes, Azoles, and Echinocandins. . . . . . 9
3. How Antibiotic Dosages Are Determined Using Susceptibility Data,
Pharmacodynamics, and Treatment Outcomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
4. Approach to Antibiotic Therapy of Drug-Resistant Gram-negative Bacilli
and Methicillin-Resistant Staphylococcus aureus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
5. Antimicrobial Therapy for Newborns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
A. Recommended Therapy for Selected Newborn Conditions. . . . . . . . . . . . . . . . . . . . . . . . 30
B. Antimicrobial Dosages for Neonates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
C. Aminoglycosides. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
D. Vancomycin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
E. Use of Antimicrobials During Pregnancy or Breastfeeding . . . . . . . . . . . . . . . . . . . . . . . . 56
6. Antimicrobial Therapy According to Clinical Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
A. Skin and Soft Tissue Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
B. Skeletal Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
C. Eye Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
D. Ear and Sinus Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
E. Oropharyngeal Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
F. Lower Respiratory Tract Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

G. Cardiovascular Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
H. Gastrointestinal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .101
I. Genital and Sexually Transmitted Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
J. Central Nervous System Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
K. Urinary Tract Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
L. Miscellaneous Systemic Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
7. Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens. . . . . . . . .127
A. Common Bacterial Pathogens and Usual Pattern of Susceptibility to
Antibiotics (Gram Positive). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
B. Common Bacterial Pathogens and Usual Pattern of Susceptibility to
Antibiotics (Gram Negative). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
C. Common Bacterial Pathogens and Usual Pattern of Susceptibility to
Antibiotics (Anaerobes) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .132
D. Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens. . . . . . . . 134

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vi — Contents

8. Preferred Therapy for Specific Fungal Pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155
A. Overview of More Common Fungal Pathogens and Their Usual Pattern
of Antifungal Susceptibilities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
B. Systemic Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
C. Localized Mucocutaneous Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .172
9. Preferred Therapy for Specific Viral Pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
A. Overview of Non-HIV, Non-Hepatitis B or C Viral Pathogens and
Usual Pattern of Susceptibility to Antivirals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

B. Overview of Hepatitis B or C Viral Pathogens and Usual Pattern of
Susceptibility to Antivirals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .174
C. Preferred Therapy for Specific Viral Pathogens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .176
10. Preferred Therapy for Specific Parasitic Pathogens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
A. Selected Common Pathogenic Parasites and Suggested
Agents for Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190
B. Preferred Therapy for Specific Parasitic Pathogens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .192
11. Alphabetic Listing of Antimicrobials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
A. Systemic Antimicrobials With Dosage Forms and Usual Dosages. . . . . . . . . . . . . . . 213
B. Topical Antimicrobials (Skin, Eye, Ear, Mucosa) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
12. Antibiotic Therapy for Children Who Are Obese . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .241
13. Sequential Parenteral-Oral Antibiotic Therapy (Oral Step-down Therapy)
for Serious Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .245
14. Antimicrobial Prophylaxis/Prevention of Symptomatic Infection . . . . . . . . . . . . . . . 247
A. Postexposure Antimicrobial Prophylaxis to Prevent Infection. . . . . . . . . . . . . . . . . . . 249
B. Long-term Antimicrobial Prophylaxis to Prevent Symptomatic
New Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .256
C. Prophylaxis of Symptomatic Disease in Children Who Have Asymptomatic
Infection/Latent Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
D. Surgical/Procedure Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .258
Appendix: Nomogram for Determining Body Surface Area. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .265
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289

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vii


Introduction
We are now in our 25th edition of Nelson’s Pediatric Antimicrobial Therapy, a tribute to
John Nelson’s belief that advice on treatment of children with infections should be clear
and concise! Although no new oral anti-infective agents have been approved in the
United States recently, several antibiotics in many classes that completed adult studies
are now entering pediatric clinical trials, particularly those for multidrug-resistant
Gram-negative bacilli. The contributing editors, all very active in clinical work, have
updates in their sections with relevant new recommendations based on current published data, guidelines, and clinical experience. We hope that the reference list for each
chapter provides the available evidence to support our recommendations, for those who
wish to see the data.
For those who use the Nelson’s app, you may have noticed a new “feel” to the app, which
is now written in one of the Apple programing languages by Dr Howard Smart, a fulltime office-based pediatrician and the chief of pediatrics at the Sharp Rees-Stealy multispecialty medical group in San Diego, CA. With the support of the American Academy
of Pediatrics (AAP) (particularly Peter Lynch) and the editors, we are putting more of
Howard’s enhancements in this 2019 edition. So substantial are his contributions to the
app, the book (from the perspective of an office-based pediatrician), and the development of future Nelson’s digital versions that the editors and the AAP have unanimously
asked Howard to join us officially as a contributing editor. We believe that his skills
(clinical and digital) are an essential part of what we all hope the AAP Nelson’s book can
and should be.
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
wish to continue to acknowledge their advice each year in this Introduction. We con­
tinue to receive valuable suggestions from Drs John van den Anker and Pablo Sanchez
on antimicrobial therapy of the newborn, in support of the work done by JB Cantey and
Jason Sauberan in Chapter 5.
A pediatric hospital medicine consulting editor who is with us again this year is Dr Brian
Williams, a pediatric/adult hospitalist who trained with us at the University of
California, San Diego, School of Medicine/Rady Children’s Hospital San Diego and is
now in Madison, WI. His continuing advice on organizing information for both the
book and the app has been invaluable. He is focused, practical, and very collaborative.

We continue to harmonize the Nelson’s book with Red Book: 2018–2021 Report of the
Committee on Infectious Diseases, 31st Edition (easy to understand, given that Dr David
Kimberlin is also the editor of the Red Book). We are virtually always in sync but often
with additional explanations (that do not necessarily represent AAP policy) to allow the
reader to understand the basis for recommendations.

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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 do 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 for all to use in clinical practice.
Barrett Winston, our primary AAP editorial contact for the past few years, has done an
amazing job of organizing all the AAP staff, as well as the contributing and consulting
editors, but has now moved to other responsibilities within the AAP and is turning over
the editorial tasks to Mary Kelly, who has an impressive track record in publications.
Mary will now keep us all moving forward with the 2019 edition upgrades and enhancements as we keep looking to the long-term future of the book in partnership with the

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Introduction — ix

AAP. Peter Lynch continues to work on developing Nelson’s online, as well as the app,
and has shared considerable AAP resources with us. We 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, vice president, Publishing, and our steadfast
friends and supporters in AAP Membership, Marketing, and Publishing—Jeff Mahony,
director, 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! From the feedback we have received, the
chapter on adverse drug reactions is no longer included in this edition. We are focusing
on more common antimicrobial drug issues, such as dosing in obesity. Please send your

suggestions to
John S. Bradley, MD

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xi

Notable Changes to 2019 Nelson’s Pediatric Antimicrobial Therapy, 25th Edition
Nelson’s Pediatric Antimicrobial Therapy has been updated to incorporate new
approaches to treatment based on clinical guidelines and new publications, as well as to
be consistent with Red Book: 2018–2021 Report of the Committee on Infectious Diseases,
31st Edition. Color has been added throughout to improve navigation and help you find
the best treatment options quickly.
Antimicrobials, Antifungals, Antivirals, and Antiparasitics
• Updates to tables for susceptibility of bacterial, fungal, viral, and parasitic pathogens.
Tables are now color coded to make it easier to instantly find the best treatment
options by pathogen.
• Presents new safety data on fluoroquinolones (including moxifloxacin) in children,
supporting current policy that these drugs are appropriate for situations in which no
other drug is active against the bacterial pathogen.
• Updates for doxycycline dosing, which has been converted to kilogram-based dosing
to be consistent with US Food and Drug Administration (FDA) package label dosing.

• Provides extensive explanations of the new beta-lactam/beta-lactamase inhibitor
combinations. At least 4 new antibiotics are under investigation in children, mostly for
multidrug-resistant Gram-negative bacilli. Specific, new, and evolving recommendations about antifungal therapeutic drug levels for several invasive fungal infections are
clarified, particularly in immunocompromised children.
•Adds Candida auris as a newly emergent fungal pathogen.
• Incorporates new coccidioidomycosis guidelines to updated recommendations.
• Includes new approaches to mucormycosis, a devastating infection, based on published
data, animal models, and the extensive experience of William J. Steinbach, MD.
• Reorganizes antiviral table into 2 tables for easier reading: common viral pathogens are
in one table, and HIV, hepatitis B, and hepatitis C are in a second table.
• Updates to babesiosis to include a recent publication supporting the choice of azithromycin and atovaquone for both mild to moderate and severe infection.
• Updates, including new information on drug therapy and steroid therapy, for neurocysticercosis incorporating the Infectious Diseases Society of America (IDSA) and
American Society of Tropical Medicine and Hygiene guidelines.
• Updates for Giardia, including tinidazole and nitazoxanide as drugs of choice, based
on the IDSA guidelines for clinical management of diarrhea.

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xii — Notable Changes to 2019 Nelson’s Pediatric Antimocrobial Therapy, 25th Edition

• Updates for Chagas disease to include benznidazole, which was approved by the FDA
for use in children 2 to 12 years of age and is no longer available through the Centers
for Disease Control and Prevention (CDC). Nifurtimox continues to be available only
through the CDC.
Antimicrobial Therapy for Newborns
• Updates to the management of newborns exposed to HIV, including links to the
National Institutes of Health Web site that is continuously updated.

• Options for treatment of increasing resistance in Escherichia coli for urinary tract
infections.
• Guidance to achieve similar antibacterial activity in similar tissue sites, with a similar
safety profile, in the neonate during the ongoing cefotaxime shortage.

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1. Choosing Among Antibiotics Within a Class: Beta-lactams and
Beta-lactamase Inhibitors, Macrolides, Aminoglycosides, and
Fluoroquinolones
New drugs should be compared with others in the same class regarding (1) antimicrobial
spectrum; (2) degree of antibiotic exposure (a function of the pharmacokinetics of the
nonprotein-bound drug at the site of infection and the pharmacodynamic properties
of the drug); (3) demonstrated efficacy in adequate and well-controlled clinical trials;
(4) tolerance, toxicity, and side effects; and (5) cost. If there is no substantial benefit for
efficacy or safety for one antimicrobial over another for the isolated or presumed bacterial pathogen(s), one should opt for using an older, more extensively used agent (with
presumably better-defined efficacy and safety) that is usually less expensive and preferably
with a narrower spectrum of activity.
Beta-lactams and Beta-lactamase Inhibitors

Beta-lactam (BL)/Beta-lactamase Inhibitor (BLI) Combinations. Increasingly studied
and approved by the US Food and Drug Administration (FDA) are BL/BLI combinations
that target antibiotic resistance based on the presence of a pathogen’s beta-lactamase.
The BL antibiotic may demonstrate activity against a pathogen, but if a beta-lactamase
is present in that pathogen, it will hydrolyze the BL ring structure and inactivate the

antibiotic. The BLI is usually a BL structure, which explains why it binds readily to
certain beta-lactamases and can inhibit their activity; however, the BLI usually does not
demonstrate direct antibiotic activity itself. As amoxicillin and ampicillin were used
extensively against Haemophilus influenzae following their approval, resistance to both
antibiotics increased, based on the presence of a beta-lactamase that hydrolyzes the BL
ring of amoxicillin/ampicillin (up to 40% resistance in some regions). Clavulanate, a BLI
that binds to and inactivates the beta-lactamase, allows amoxicillin/ampicillin to “survive”
and inhibit cell wall formation, leading to the death of the organism. The oral BL/BLI
combination of amoxicillin/clavulanate, originally known as Augmentin, has been very
effective. Similar combinations, primarily intravenous (IV), have now been studied, pairing penicillins, cephalosporins, and carbapenems with other BLIs such as tazobactam,
sulbactam, and avibactam. Under investigation in children are the IV BL/BLI combinations ­ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and
imipenem relebactam.
Beta-lactam Antibiotics

Oral Cephalosporins (cephalexin, cefadroxil, cefaclor, cefprozil, cefuroxime, cefixime, cefdinir, cefpodoxime, cefditoren [tablet only], and ceftibuten). As a class, the oral
cephalosporins have the advantage over oral penicillins of somewhat greater spectrum of
activity. The serum half-lives of cefpodoxime, ceftibuten, and cefixime are greater than
2 hours. This pharmacokinetic feature accounts for the fact that they may be given in
1 or 2 doses per day for certain indications, particularly otitis media, where the middle
ear fluid half-life is likely to be much longer than the serum half-life. For more resistant
pathogens, twice daily is preferred (see Chapter 3). The spectrum of activity increases for

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1

Gram-negative organisms as one goes from the first-generation cephalosporins (cephalexin and cefadroxil), to the second generation (cefaclor, cefprozil, and cefuroxime)
that demonstrates activity against Haemophilus influenzae (including beta-lactamase–­
producing strains), to the third-generation agents (cefdinir, cefixime, cefpodoxime,
and ceftibuten) that have enhanced coverage of many enteric Gram-negative bacilli
(Escherichia coli, Klebsiella spp). However, ceftibuten and cefixime, in particular, have a
disadvantage of less activity against Streptococcus pneumoniae than the others, particularly against penicillin (BL) non-susceptible strains. No oral fourth- or fifth-generation
cephalosporins (see the Parenteral Cephalosporins section) currently exist (no activity against Pseudomonas or methicillin-resistant Staphylococcus aureus [MRSA]). The
palatability of generic versions of these products may not have the same better-tasting
characteristics as the original products.
Parenteral Cephalosporins. First-generation cephalosporins, such as cefazolin, are used
mainly for treatment of Gram-positive infections caused by S aureus (excluding MRSA)
and group A streptococcus and for surgical prophylaxis; the Gram-negative spectrum is
limited but more extensive than ampicillin. Cefazolin is well tolerated on intramuscular
or IV injection.
A second-generation cephalosporin (cefuroxime) and the cephamycins (cefoxitin and
cefotetan) provide increased activity against many Gram-negative organisms, particularly
Haemophilus and E coli. Cefoxitin has, in addition, activity against approximately 80%
of strains of Bacteroides fragilis and can be considered for use in place of the more active
agents, like metronidazole or carbapenems, when that organism is implicated in nonserious disease.
Third-generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime) all have
enhanced potency against many enteric Gram-negative bacilli. As with all cephalosporins,
at readily achievable serum concentrations, they are less active against enterococci and

Listeria; only ceftazidime has significant activity against Pseudomonas. Cefotaxime and
ceftriaxone have been used very successfully to treat meningitis caused by pneumococcus (mostly penicillin-susceptible strains), H influenzae type b, meningococcus, and
susceptible strains of E coli meningitis. These drugs have the greatest usefulness for treating Gram-negative bacillary infections due to their safety, compared with other classes of
antibiotics (including aminoglycosides). Because ceftriaxone is excreted, to a large extent,
via the liver, it can be used with little dosage adjustment in patients with renal failure.
With a serum half-life of 4 to 7 hours, it can be given once a day for all infections, including meningitis, that are caused by susceptible organisms.
Cefepime, a fourth-generation cephalosporin approved for use in children in 1999,
exhibits (1) enhanced antipseudomonal activity over ceftazidime; (2) the Gram-positive
activity of second-generation cephalosporins; (3) better activity against Gram-negative
enteric bacilli; and (4) stability against the inducible ampC beta-lactamases of Enterobacter and Serratia (and some strains of Proteus and Citrobacter) that can hydrolyze
third-generation cephalosporins. It can be used as single-drug antibiotic therapy against

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2019 Nelson’s Pediatric Antimicrobial Therapy — 3

Ceftaroline is a fifth-generation cephalosporin, the first of the cephalosporins with activity against MRSA. Ceftaroline was approved by the FDA in December 2010 for adults
and approved for children in June 2016 for treatment of complicated skin infections
(including MRSA) and community-acquired pneumonia. The pharmacokinetics of ceftaroline have been evaluated in all pediatric age groups, including neonates and children
with cystic fibrosis; clinical studies for pediatric community-acquired pneumonia and
complicated skin infection have now been published.1 Based on these published data,
review by the FDA, and post-marketing experience for infants and children 2 months
and older, ceftaroline should be as effective and safer than vancomycin for treatment of
MRSA infections. Just as BLs are preferred over vancomycin for methicillin-susceptible
S aureus infections, ceftaroline should be considered preferred treatment over vancomycin for MRSA infection. Neither renal function nor drug levels need to be followed with
ceftaroline therapy.
Penicillinase-Resistant Penicillins (dicloxacillin [capsules only]; nafcillin and oxacillin

[parenteral only]). “Penicillinase” refers specifically to the beta-lactamase produced by
S aureus in this case and not those produced by Gram-negative bacteria. These anti­
biotics are active against penicillin-resistant S aureus but not against MRSA. Nafcillin
differs pharmacologically from the others in being excreted primarily by the liver rather
than by the kidneys, which may explain the relative lack of nephrotoxicity compared with
methicillin, which is no longer available in the United States. Nafcillin pharmacokinetics
are erratic in persons with liver disease, and the drug is often painful with IV infusion.
Antipseudomonal and Anti-enteric Gram-negative BLs (piperacillin/tazobactam,
aztreonam, ceftazidime, cefepime, meropenem, and imipenem). Piperacillin/­tazobactam
(Zosyn), ceftolozane/tazobactam (Zerbaxa), and ceftazidime/avibactam (Avycaz)
represent BL/BLI combinations, as noted previously. The BLI (clavulanic acid, tazobactam, or avibactam in these combinations) binds irreversibly to and neutralizes specific
beta-­lactamase enzymes produced by the organism. The combination only adds to
the spectrum of the original antibiotic when the mechanism of resistance is a betalactamase enzyme and only when the BLI is capable of binding to and inhibiting that
particular organism’s beta-lactamase enzyme(s). The combinations extend the spectrum
of activity of the primary antibiotic to include many beta-lactamase–positive bacteria,
including some strains of enteric Gram-negative bacilli (E coli, Klebsiella, and Enterobacter), S aureus, and B fragilis. Piperacillin/tazobactam, ceftolozane/tazobactam, and
­ceftazidime/avibactam may still be inactive against Pseudomonas because their BLIs may
not effectively inhibit all the many relevant beta-lactamases of Pseudomonas.

1
Choosing Among Antibiotics Within a Class: Beta-lactams and Beta-lactamase Inhibitors, Macrolides, Aminoglycosides, and Fluoroquinolones

these pathogens, rather than paired with an aminoglycoside, as is commonly done with
third-generation cephalosporins to decrease the emergence of ampC-resistant clones.

Pseudomonas has an intrinsic capacity to develop resistance following exposure to any
BL, based on the activity of several inducible chromosomal beta-lactamases, upregulated
efflux pumps, and changes in the permeability of the cell wall, as well as mutational
changes in the antibacterial target sites. Because development of resistance during therapy


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1

is not uncommon (particularly beta-lactamase–mediated resistance against piperacillin
or ceftazidime), an aminoglycoside such as tobramycin is often used in combination,
assuming that the tobramycin may kill strains developing resistance to the BLs. Cefepime,
meropenem, and imipenem are relatively stable to the beta-lactamases induced while on
therapy and can be used as single-agent therapy for most Pseudomonas infections, but
resistance may still develop to these agents based on other mechanisms of resistance. For
Pseudomonas infections in compromised hosts or in life-threatening infections, these
drugs, too, should be used in combination with an aminoglycoside or a second active
agent. The benefits of the additional antibiotic should be weighed against the potential for
additional toxicity and alteration of host flora.
Aminopenicillins (amoxicillin and amoxicillin/clavulanate [oral formulations only, in
the United States], ampicillin [oral and parenteral], and ampicillin/sulbactam [parenteral
only]). Amoxicillin is very well absorbed, good tasting, and associated with very few side
effects. Augmentin is a combination of amoxicillin and clavulanate (as noted previously)
that is available in several fixed proportions that permit amoxicillin to remain active
against many beta-lactamase–producing bacteria, including H influenzae and S aureus
(but not MRSA). Amoxicillin/clavulanate has undergone many changes in formulation
since its introduction. The ratio of amoxicillin to clavulanate was originally 4:1, based

on susceptibility data of pneumococcus and Haemophilus during the 1970s. With the
emergence of penicillin-resistant pneumococcus, recommendations for increasing the
dosage of amoxicillin, particularly for upper respiratory tract infections, were made.
However, if one increases the dosage of clavulanate even slightly, the incidence of diarrhea
increases dramatically. If one keeps the dosage of clavulanate constant while increasing
the dosage of amoxicillin, one can treat the relatively resistant pneumococci while not
increasing gastrointestinal side effects of the combination. The original 4:1 ratio is present
in suspensions containing 125-mg and 250-mg amoxicillin/5 mL and the 125-mg and
250-mg chewable tablets. A higher 7:1 ratio is present in the suspensions containing
200-mg and 400-mg amoxicillin/5 mL and in the 200-mg and 400-mg chewable tablets.
A still higher ratio of 14:1 is present in the suspension formulation Augmentin ES-600
that contains 600-mg amoxicillin/5 mL; this preparation is designed to deliver 90 mg/kg/
day of amoxicillin, divided twice daily, for the treatment of ear (and sinus) infections. The
high serum and middle ear fluid concentrations achieved with 45 mg/kg/dose, combined
with the long middle ear fluid half-life (4–6 hours) of amoxicillin, allow for a therapeutic
antibiotic exposure to pathogens in the middle ear with a twice-daily regimen. However,
the prolonged half-life in the middle ear fluid is not necessarily found in other infection
sites (eg, skin, lung tissue, joint tissue), for which dosing of amoxicillin and Augmentin
should continue to be 3 times daily for most susceptible pathogens.
For older children who can swallow tablets, the amoxicillin to clavulanate ratios are as
follows: 500-mg tablet (4:1); 875-mg tablet (7:1); 1,000-mg tablet (16:1).
Sulbactam, another BLI like clavulanate, is combined with ampicillin in the parenteral
formulation Unasyn. The cautions regarding spectrum of activity for piperacillin/­
tazobactam with respect to the limitations of the BLI in increasing the spectrum of

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2019 Nelson’s Pediatric Antimicrobial Therapy — 5

Carbapenems. Meropenem, imipenem, doripenem, and ertapenem are carbapenems with a broader spectrum of activity than any other class of BL currently available.
Meropenem, imipenem, and ertapenem are approved by the FDA for use in children.
At present, we recommend them for treatment of infections caused by bacteria resistant
to standard therapy or for mixed infections involving aerobes and anaerobes. Imipenem
has greater central nervous system (CNS) irritability compared with other carbapenems,
leading to an increased risk of seizures in children with meningitis, but this is not clinically significant in children without underlying CNS inflammation. Meropenem was
not associated with an increased rate of seizures, compared with cefotaxime in children
with meningitis. Imipenem and meropenem are active against virtually all coliform
bacilli, including cefotaxime-resistant (extended spectrum beta-lactamase–producing or
ampC-producing) strains, against Pseudomonas aeruginosa (including most ceftazidimeresistant strains), and against anaerobes, including B fragilis. While ertapenem lacks the
excellent activity against P aeruginosa of the other carbapenems, it has the advantage of a
prolonged serum half-life, which allows for once-daily dosing in adults and children aged
13 years and older and twice-daily dosing in younger children. Newly emergent strains
of Klebsiella pneumoniae contain K pneumoniae carbapenemases that degrade and
inactivate all the carbapenems. These strains, as well as strains carrying the less common
New Delhi metallo-beta-lactamase, which is also active against carbapenems, have begun
to spread to many parts of the world, reinforcing the need to keep track of your local
antibiotic susceptibility patterns. Carbapenems that have been paired with BLIs, as noted
previously, may only inhibit one type of carbapenemase.
Macrolides

Erythromycin is the prototype of macrolide antibiotics. Almost 30 macrolides have been
produced, but only 3 are FDA approved for children in the United States: erythromycin,
azithromycin (also called an azalide), and clarithromycin, while a fourth, telithromycin
(also called a ketolide), is approved for adults and only available in tablet form. As a class,
these drugs achieve greater concentrations intracellularly than in serum, particularly
with azithromycin and clarithromycin. As a result, measuring serum concentrations is
usually not clinically useful. Gastrointestinal intolerance to erythromycin is caused by

the breakdown products of the macrolide ring structure. This is much less of a problem
with azithromycin and clarithromycin. Azithromycin, clarithromycin, and telithromycin
extend the clinically relevant activity of erythromycin to include Haemophilus; azithromycin and clarithromycin also have substantial activity against certain mycobacteria.
Azithromycin is also active in vitro and effective against many enteric Gram-negative
pathogens, including Salmonella and Shigella.

1
Choosing Among Antibiotics Within a Class: Beta-lactams and Beta-lactamase Inhibitors, Macrolides, Aminoglycosides, and Fluoroquinolones

activity also apply to ampicillin/sulbactam, in which ampicillin does not even have the
extended activity against the enteric bacilli seen with piperacillin or ceftazidime.

Aminoglyciaxone/
Cefotaxime

Meropenem/
Imipenem

Piperacillin/
Tazobactam

Metronidazole

Clindamycin

Vancomycin

++

++


++

++

++

++

—

++

++

++

+

0

±

++

++

++

+


++

—

++

0

++

—

++

Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens

7

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7

D. PREFERRED THERAPY FOR SPECIFIC BACTERIAL AND MYCOBACTERIAL PATHOGENS
Organism

Clinical Illness


Drug of Choice (evidence grade)
Meropenem (BIII) or other
carbapenem

Alternatives
Use culture results to guide therapy:
ceftazidime, amp/sul, pip/tazo, TMP/SMX,
ciprofloxacin, tigecycline, colistin/
polymyxin B.
Watch for emergence of resistance during
therapy, including to colistin.
Consider combination therapy for lifethreatening infection.4
Inhaled colistin for pneumonia caused by
MDR strains (BIII).

11/12/18 11:46 AM

Acinetobacter baumannii1–4

Sepsis, meningitis,
nosocomial pneumonia,
wound infection

Actinomyces israelii5

Actinomycosis (cervicofacial, Penicillin G; ampicillin (CIII)
thoracic, abdominal)

Amoxicillin, doxycycline, clindamycin,

ceftriaxone, meropenem, pip/tazo, linezolid

Aeromonas hydrophila6

Diarrhea

Ciprofloxacin (CIII)

Azithromycin, cefepime, TMP/SMX

Sepsis, cellulitis,
necrotizing fasciitis

Cefepime (BIII)

Meropenem, ciprofloxacin, TMP/SMX

Aggregatibacter (formerly
Actinobacillus)
actinomycetemcomitans7

Periodontitis, abscesses
(including brain),
endocarditis

Ceftriaxone (CIII)

Ampicillin/amoxicillin for beta-lactamase–
negative strains, or amox/clav, doxycycline,
TMP/SMX, ciprofloxacin


Anaplasma (formerly
Ehrlichia)
phagocytophilum8,9

Human granulocytic
anaplasmosis

Doxycycline (all ages) (AII)

Rifampin, levofloxacin

Arcanobacterium
haemolyticum10

Pharyngitis, cellulitis,
Lemierre syndrome

Azithromycin; penicillin (BIII)

Erythromycin, amoxicillin, ceftriaxone,
clindamycin, doxycycline, vancomycin

Bacillus anthracis11

Anthrax (cutaneous,
gastrointestinal,
inhalational,
meningoencephalitis)


Ciprofloxacin (regardless of age)
(AIII).
For invasive, systemic infection, use
combination therapy.

Doxycycline, amoxicillin, levofloxacin,
clindamycin, penicillin G, vancomycin,
meropenem.
Bioterror strains may be antibiotic resistant.

Bacillus cereus or subtilis12,13

Sepsis; toxin-mediated

Vancomycin (BIII)

Clindamycin, ciprofloxacin, linezolid,

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Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens


meningoencephalitis)

Bioterror strains may be antibiotic resistant.

combination therapy.


ch07-Nelson-2019_127-154.indd 135

Vancomycin (BIII)

Clindamycin, ciprofloxacin, linezolid,
daptomycin

Bacteroides fragilis14,15

Peritonitis, sepsis,
abscesses

Metronidazole (AI)

Meropenem or imipenem (AI); pip/tazo (AI);
amox/clav (BII).
Recent surveillance suggests resistance of up
to 25% for clindamycin.

Bacteroides, other spp14,15

Pneumonia, sepsis,
abscesses

Metronidazole (BII)

Meropenem or imipenem; penicillin G or
ampicillin if beta-lactamase negative


Bartonella henselae16,17

Cat-scratch disease

Azithromycin for lymph node
disease (BII); gentamicin in
combination with TMP/SMX AND
rifampin for invasive disease (BIII)

Cefotaxime, ciprofloxacin, doxycycline

Bartonella quintana17,18

Bacillary angiomatosis,
peliosis hepatis

Gentamicin plus doxycycline (BIII);
erythromycin; ciprofloxacin (BIII)

Azithromycin, doxycycline

Bordetella pertussis,
parapertussis19,20

Pertussis

Azithromycin (AIII); erythromycin
(BII)

Clarithromycin, TMP/SMX, ciprofloxacin (in

vitro data)

Borrelia burgdorferi, Lyme
disease21–23

Treatment based on stage
of infection (See Lyme
disease in Chapter 6.)

Doxycycline if .7 y (AII); amoxicillin
or cefuroxime in children #7 y
(AIII); ceftriaxone IV for CNS/
meningitis (AII)

Borrelia hermsii, turicatae,
parkeri, tick-borne
relapsing fever24,25

Relapsing fever

Doxycycline for all ages (AIII)

Penicillin or erythromycin in children
intolerant of doxycycline (BIII)

Borrelia recurrentis, louseborne relapsing fever24,25

Relapsing fever

Single-dose doxycycline for all ages

(AIII)

Penicillin or erythromycin in children
intolerant of doxycycline (BIII). Amoxicillin;
ceftriaxone.

Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens

2019 Nelson’s Pediatric Antimicrobial Therapy — 135

Sepsis; toxin-mediated
gastroenteritis

7

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Bacillus cereus or subtilis12,13


7

D. PREFERRED THERAPY FOR SPECIFIC BACTERIAL AND MYCOBACTERIAL PATHOGENS (continued)
Organism

11/12/18 11:46 AM

Drug of Choice (evidence grade)

Alternatives


Brucella spp26–28

Brucellosis
(See Chapter 6.)

Clinical Illness

Doxycycline AND rifampin (BIII); OR,
for children #7 y: TMP/SMX AND
rifampin (BIII)

For serious infection: doxycycline AND
gentamicin AND rifampin; or TMP/SMX AND
gentamicin AND rifampin (AIII). May require
extended therapy (months).

Burkholderia cepacia
complex29–31

Pneumonia, sepsis in
immunocompromised
children; pneumonia in
children with cystic
fibrosis32

Meropenem (BIII); for severe disease,
ADD tobramycin (although may be
in vitro resistant to aminoglyco­
sides) AND TMP/SMX (AIII).


Imipenem, doxycycline, ceftazidime, pip/tazo,
ciprofloxacin, TMP-SMX.
Aerosolized antibiotics may provide higher
concentrations in lung.

Burkholderia
pseudomallei33–35

Melioidosis

Meropenem (AIII) or ceftazidime
(BIII), followed by prolonged TMP/
SMX for 12 wk (AII)

TMP/SMX, doxycycline, or amox/clav for
chronic disease

Campylobacter fetus36,37

Sepsis, meningitis in the
neonate

Meropenem (BIII)

Cefotaxime, gentamicin, erythromycin,
ciprofloxacin

Campylobacter jejuni38,39


Diarrhea

Azithromycin (BII); erythromycin (BII)

Doxycycline, ciprofloxacin (very high rates of
ciprofloxacin-resistant strains in Thailand,
Hong Kong, and Spain)

Capnocytophaga
canimorsus40,41

Sepsis after dog bite
(increased risk with
asplenia)

Pip/tazo OR meropenem; amox/clav
(BIII)

Clindamycin, linezolid, penicillin G,
ciprofloxacin

Capnocytophaga ochracea42

Sepsis, abscesses

Clindamycin (BIII); amox/clav (BIII)

Meropenem, pip/tazo, ciprofloxacin

Chlamydia trachomatis43–45


Lymphogranuloma
venereum

Doxycycline (AII)

Azithromycin, erythromycin

Urethritis, cervicitis

Doxycycline (AII)

Azithromycin, erythromycin, ofloxacin

Inclusion conjunctivitis of
newborn

Azithromycin (AIII)

Erythromycin

Pneumonia of infancy

Azithromycin (AIII)

Erythromycin, ampicillin

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newborn

ch07-Nelson-2019_127-154.indd 137

Pneumonia of infancy

Azithromycin (AIII)

Erythromycin, ampicillin

Trachoma

Azithromycin (AI)

Doxycycline, erythromycin

Chlamydophila (formerly
Chlamydia)
pneumoniae43,44,46,47

Pneumonia

Azithromycin (AII); erythromycin (AII)

Doxycycline, ciprofloxacin


Chlamydophila (formerly
Chlamydia) psittaci48

Psittacosis

Doxycycline for .7 y; azithromycin
(AIII) OR erythromycin (AIII) for
#7 y

Doxycycline, levofloxacin

Chromobacterium
violaceum49,50

Sepsis, pneumonia,
abscesses

Meropenem AND ciprofloxacin (AIII)

Imipenem, TMP/SMX

Citrobacter koseri (formerly
diversus) and freundii51,52

Meningitis, sepsis

Meropenem (AIII) for ampC betalactamase resistance

Cefepime, ciprofloxacin, pip/tazo, ceftriaxone
AND gentamicin, TMP/SMX

Carbapenem-resistant strains now reported
2019 Nelson’s Pediatric Antimicrobial Therapy — 137

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Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens


7

D. PREFERRED THERAPY FOR SPECIFIC BACTERIAL AND MYCOBACTERIAL PATHOGENS (continued)
Organism

Clinical Illness

Drug of Choice (evidence grade)

Alternatives

Botulism: foodborne;
wound; potentially
bioterror related

Botulism antitoxin heptavalent
(equine) types A–G FDA approved
in 2013 (www.fda.gov/downloads/
BiologicsBloodVaccines/
BloodBloodProducts/

ApprovedProducts/
LicensedProductsBLAs/
FractionatedPlasmaProducts/
UCM345147.pdf; accessed October
3, 2018)
No antibiotic treatment except for
wound botulism when treatment
for vegetative organisms can be
provided after antitoxin
administered (no controlled data)

For more information, call your state health
department or the CDC clinical emergency
botulism service, 770/488-7100 (https://
www.cdc.gov/botulism/health-professional.
html; accessed October 3, 2018).
For bioterror exposure, treatment
recommendations per www.cdc.gov.

Infant botulism

Human botulism immune globulin
for infants (BabyBIG) (AII)
No antibiotic treatment

BabyBIG available nationally from the
California Department of Public Health at
510/231-7600 (www.infantbotulism.org;
accessed October 3, 2018)


Clostridium difficile56–58

Antibiotic-associated
colitis (See Chapter 6,
Table 6H,
Gastrointestinal
Infections, Clostridium
difficile.)

Metronidazole PO for mild to
moderate infection (AI)

Vancomycin PO ± metronidazole PO for
severe infection.
Vancomycin PO for metronidazole failures.
Stop the predisposing antimicrobial therapy,
if possible.
New pediatric data on fidaxomicin PO.59
No pediatric data on fecal transplantation for
recurrent disease.

Clostridium perfringens60,61

Gas gangrene/necrotizing

Penicillin G AND clindamycin for

Meropenem, metronidazole, clindamycin

Clostridium botulinum53–55


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ch07-Nelson-2019_127-154.indd 139

Penicillin G AND clindamycin for
invasive infection (BII); no
antimicrobials indicated for
foodborne illness

Meropenem, metronidazole, clindamycin
monotherapy
No defined benefit of hyperbaric oxygen over
aggressive surgery/antibiotic therapy

Clostridium tetani62,63

Tetanus

Tetanus immune globulin 3,000–
6,000 U IM, with part injected
directly into the wound (IVIG at
200–400 mg/kg if TIG not

available)
Metronidazole (AIII) OR penicillin G
(BIII)

Prophylaxis for contaminated wounds: 250 U
IM for those with ,3 tetanus
immunizations.
Start/continue immunization for tetanus.
Alternative antibiotics: meropenem;
doxycycline, clindamycin.

Corynebacterium
diphtheriae64

Diphtheria

Diphtheria equine antitoxin
(available through CDC under an
investigational protocol [www.cdc.
gov/diphtheria/dat.html; accessed
October 3, 2018]) AND
erythromycin or penicillin G (AIII)

Antitoxin from the CDC Emergency
Operations Center, 770/488-7100; protocol:
www.cdc.gov/diphtheria/downloads/
protocol.pdf (accessed October 3, 2018)

Corynebacterium jeikeium65,66


Sepsis, endocarditis

Vancomycin (AIII)

Penicillin G AND gentamicin, daptomycin,
tigecycline, linezolid

Corynebacterium
minutissimum67,68

Erythrasma; bacteremia in
compromised hosts

Erythromycin PO for erythrasma
(BIII); vancomycin IV for
bacteremia (BIII)

Topical clindamycin for cutaneous infection;
meropenem, penicillin/ampicillin,
ciprofloxacin

Coxiella burnetii69,70

Q fever (See Chapter 6,
Table 6L,
Miscellaneous
Systemic Infections, Q
fever.)

Acute infection: doxycycline (all

ages) (AII)
Chronic infection: TMP/SMX AND
doxycycline (BII); OR levofloxacin
AND rifampin

Alternative for acute infection: TMP/SMX

Preferred Therapy for Specific Bacterial and Mycobacterial Pathogens

2019 Nelson’s Pediatric Antimicrobial Therapy — 139

Gas gangrene/necrotizing
fasciitis/sepsis (also
caused by Clostridium
sordellii, Clostridium
septicum, Clostridium
novyi)
Food poisoning

7

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Clostridium perfringens60,61


7

D. PREFERRED THERAPY FOR SPECIFIC BACTERIAL AND MYCOBACTERIAL PATHOGENS (continued)
Organism

Ehrlichia chaffeensis9
Ehrlichia muris71,72

Clinical Illness
Human monocytic
ehrlichiosis

Drug of Choice (evidence grade)
Doxycycline (all ages) (AII)

Alternatives
Rifampin

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Ehrlichia ewingii 9

E ewingii ehrlichiosis

Doxycycline (all ages) (AII)

Rifampin

Eikenella corrodens73,74

Human bite wounds;
abscesses, meningitis,
endocarditis

Amox/clav; meropenem/imipenem;

ceftriaxone
For beta-lactamase–negative strains:
ampicillin; penicillin G (BIII)

Pip/tazo, amp/sul, ciprofloxacin
Resistant to clindamycin, cephalexin,
erythromycin

Elizabethkingia (formerly
Chryseobacterium)
meningoseptica75,76

Sepsis, meningitis
(particularly in
neonates)

Levofloxacin; TMP/SMX (BIII)

Add rifampin to another active drug; pip/tazo.

Enterobacter spp52,77,78

Sepsis, pneumonia,
wound infection, UTI

Cefepime; meropenem; pip/tazo (BII)

Ertapenem, imipenem, cefotaxime or
ceftriaxone AND gentamicin, TMP/SMX,
ciprofloxacin

Newly emerging carbapenem-resistant strains
worldwide79

Enterococcus spp80–82

Endocarditis, UTI, intraabdominal abscess

Ampicillin AND gentamicin (AI);
bactericidal activity present with
combination, not with ampicillin
or vancomycin alone

Vancomycin AND gentamicin.
For strains that are resistant to gentamicin on
synergy testing, use streptomycin or other
active aminoglycoside for invasive
infections.
For vancomycin-resistant strains that are also
ampicillin resistant: daptomycin OR
linezolid.81,82

Erysipelothrix rhusiopathiae83

Cellulitis (erysipeloid),
sepsis, abscesses,
endocarditis84

Invasive infection: ampicillin (BIII);
penicillin G (BIII)
Cutaneous infection: penicillin V;

amoxicillin; clindamycin

Ceftriaxone, meropenem, ciprofloxacin,
erythromycin
Resistant to vancomycin, daptomycin, TMP/
SMX

Escherichia coli

UTI, community acquired,

A 2nd- or 3rd-generation

Amoxicillin; TMP/SMX if susceptible.

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