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THE HARRIET LANE
HANDBOOK OF PEDIATRIC
ANTIMICROBIAL THERAPY
THE HARRIET LANE
HANDBOOK OF PEDIATRIC
ANTIMICROBIAL THERAPY
Second Edition

Julia A. McMillan, MD
Professor of Pediatrics...
1600 John F. Kennedy Blvd.
Ste 1800
Philadelphia, PA 19103-2899
THE HARRIET LANE HANDBOOK OF PEDIATRIC
ANTIMICROBIAL THERA...
DEDICATION

We dedicate this second edition of
The Harriet Lane Handbook of Pediatric
Antimicrobial Therapy to the clinici...
Contributors
Karen C. Carroll, MD
Director, Division of Medical Microbiology
Director, Medical Microbiology Fellowship Pro...
viii    Contributors

Melissa D. Makii, PharmD, BCPS
Clinical Pharmacy Specialist
Pediatric Oncology
Department of Pharmac...
Preface

This second edition of The Harriet Lane Handbook of Pediatric
Antimicrobial Therapy was, like the first edition, ...
x    Preface
Decisions regarding antimicrobial therapy for children require an
understanding of biologic development, mech...
Notes and Abbreviations
Used in Tables

TABLE 1-1
*Some recommendations are for antibiotics that are not approved by
the U...
xiv    Notes and Abbreviations Used in Tables
†

Intramuscular streptomycin is usually recommended; if not available,
kana...
Notes and Abbreviations Used in Tables    xv
TABLE 1-6
Some recommendations are for antibiotics that are not approved by t...
xvi    Notes and Abbreviations Used in Tables
β-lactam plus β-lactamase inhibitor; CGD, chronic granulomatous disease;
CMV...
Notes and Abbreviations Used in Tables    xvii
rate; CNS, central nervous system; CVVH, continuous venovenous
hemofiltrati...
xviii    Notes and Abbreviations Used in Tables
increase in exposure observed with an increasing dose; however, linear
pha...
Notes and Abbreviations Used in Tables    xix
TABLE 9-1
Observe patient for 30 min, then give full therapeutic dose by the...
xx    Notes and Abbreviations Used in Tables
TABLE 9-12
*Interval between doses is 15 min.
NA, Not applicable.
TABLE 9-14
...
Chapter 1 
Infectious Agents and Drugs
of Choice
Julia A. McMillan, MD, and
George K. Siberry, MD, MPH

1
All

All

All

Aggregatibacter
actinomycetemcomitans
(formerly Actinobacillus
sp.)

Actinomyces israeli and
other species
...
Any

Disseminated

Disseminated

All

All

Pregnant

Rifampin or
Doxycycline

Doxycycline

Ceftazidime or
Meropenem

All: ...
All

All

All

Bacillus anthracis
(potential BT agent)

Bacillus cereus

Host Category

Arcanobacterium
haemolyticum

Path...
All

Immunocompetent

Bartonella henselae (cat
scratch disease)

Host Category

Bacteroides: fragilis
group

Pathogen

TMP...
All

Bordetella pertussis,
parapertussis

Respiratory

Erythromycin or
Azithromycin or
Clarithromycin

Rifampin

Chronic (...
Borrelia burgdorferi

Pathogen

Doxycycline
or
Amoxicillin

Doxycycline

Doxycycline

Doxycycline

Repeat initial
prescrip...
Pathogen
Borrelia burgdorferi
(Continued)

Amoxicillin

Repeat initial
prescription or
Ceftriaxone

Arthritis—initial

Art...
<8 yr old, or
pregnant

TMP/SMX +
rifampin +
gentamicin

Doxycycline +
rifampin +
gentamicin

Meningitis or
endocarditis
4...
All

Southeast Asia,
Australia, India,
Central America

Children

Burkholderia mallei
(potential BT agent)

Burkholderia
p...
Chlamydophila
(Chlamydia)
pneumoniae

Any

Pneumonia

All

Capnocytophaga
ochracea

Any

Invasive

Indication/ Type
of Inf...
Chlamydia trachomatis

Chlamydophila
(Chlamydia) psittaci

Pathogen

Urethritis,
cervicitis,
proctitis

PID

Epididymitis
...
All

All

Infant

Citrobacter spp.

Clostridium botulinum

Host Category

Chromobacterium
violaceum

Pathogen

Variable

2...
All

All

All

All

Clostridium difficile

Clostridium tetani

Clostridium perfringens,
other species

Host Category

Clos...
All

All

Corynebacterium
jeikeium, other species

Host Category

Corynebacterium
diphtheriae

Pathogen

Any

Any

Indicat...
All

All

All

All

All

Edwardsiella tarda

Ehrlichia chaffeensis and
Ehrlichia ewingii

Eikenella corrodens

Elizabethki...
All

All

All

All

Enterococcus faecalis
and faecium (not
vancomycin resistant)

Enterococcus, vancomycin
resistant (VRE)...
Escherichia coli

Pathogen

All

Host Category

PCS3

PCS3

Amoxicillin or
TMP/SMX

PCS 3 or
OCS3

Sepsis

Cystitis

Pyelo...
Escherichia coli—
enterohemorrhagic
(STEC)
Escherichia coli—
enteroinvasive
Escherichia coli—
enterotoxigenic
Francisella ...
Haemophilus
influenzae—type b,
occasionally other types,
rarely nontypeable

Gardnerella vaginalis
(see Bacterial Vaginosi...
All

Gastritis, gastric,
and duodenal
ulcers

Endocarditis

All

Helicobacter pylori

Conjunctivitis

All

Haemophilus
inf...
All

All

Klebsiella spp.

Host Category

Kingella kingae, other
species

Pathogen

7–14 days
7–14 days
≥21 days

PCS3 or
...
Leptospira spp.
(Leptospirosis)

Legionella pneumophila

Klebsiella (formerly
Calymmatobacterium)
granulomatis

Pathogen

...
All

Morganella

Sepsis, pneumonia

Older

14 days

Ampicillin +
gentamicin

Variable
Variable
≥10 days
≥10 days
≥10 days
...
Host Category

Indication/ Type
of Infection

All

All

Mycoplasma pneumoniae

Neisseria gonorrhoeae

Urethritis,
pharyngi...
Neisseria meningitidis

Neisseria gonorrhoeae
(Coutinued)

Pathogen

All

Host Category

Ceftriaxone

Ceftriaxone
PenG or
...
Pasteurella multocida

Nocardia brasiliensis,
asteroides, other
species

Pathogen

PenG or
Ampicillin

Invasive or severe
...
All

Duration

Clindamycin

Metronidazole

GI, genitourinary

PCS3

Carbapenem

Pip/tazo or
Ampicillin/
sulbactam or
Ticar...
All

All

All

All

Proteus mirabilis

Proteus vulgaris and
other indole-positive
species

Providencia spp.

Host Category...
Host Category

All

All

All

Rickettsia rickettsii

Rickettsia akari

Rickettsia prowazekii

Pseudomonas aeruginosa, All
...
All

All

All

Rickettsia—other species

Salmonella typhi (type D)

Host Category

Rickettsia typhi

Pathogen

PCS3 or
FQ ...
Salmonella, non-typhi

Pathogen

Gastroenteritis

Infant <3 mo old;
sickle cell; splenic
dysfunction

PCS3

Meningitis

PC...
Gastroenteritis,
dysentery

Gastroenteritis,
dysentery

Bacteremia,
invasive

Child

Adult

All ages

Shigella sonnei, Shi...
Staphylococcus aureus;
methicillin-susceptible
S. aureus (MSSA)

Pathogen

All

Host Category

4–6 wk
(gentamicin
3–5 days...
Staphylococcus aureus;
methicillin-resistant S.
aureus (MRSA)

Pathogen

All

Host Category

10 days from
negative
culture...
All

All

All

Streptobacillus
moniliformis

Streptococcus
pneumoniae

Host Category

Stenotrophomonas
maltophilia

Pathog...
Pathogen

Host Category

14 days

14 days

PCS3

Vancomycin +
PCS3
+/− rifampin

Meningitis:
penicillin
nonsusceptible
and...
Pharyngitis; other
noninvasive

Invasive,
nonendocarditis

All

All

PenG IV

PenVK PO

>10 days

14–21 days
(ampicillin o...
Viridans streptococci

Pathogen

Penicillin PO or
Amoxicillin or
Ampicillin

Penicillin IV or
Ampicillin IV or
Ceftriaxone...
Viridans streptococci
(Coutinued)

Pathogen

Host Category

6 wk
6 wk

6 wk
6 wk

Ampicillin IV +
gentamicin or
Penicillin...
Treponema pallidum
(syphilis)

Pathogen

PenG benzathine
IM

Latent ≥1 yr; latent
unknown
duration; tertiary
without
neuro...
Doxycycline IV
TMP/SMX PO or
Doxycycline PO or
Ciprofloxacin PO or
Azithromycin PO

All

Symptomatic CNS
Moderate to sever...
Yersinia pestis (plague)

Vibrio vulnificus, Vibrio
parahaemolyticus, other
species
Yersinia enterocolitica,
Yersinia
pseu...
Mycobacterium
tuberculosis*

Pathogen

Pregnancy and
breast-feeding

Immunocompetent

Host Category

Treat only after
cons...
Pathogen

Latent infection

Pulmonary and
extrapulmonary,
drug-susceptible
disease (excluding
meningitis or
disseminated/
...
Mycobacterium
tuberculosis*
(Coutinued)

Pathogen

Pregnancy

Host Category

9–12 mo
9–12 mo
2 mo
2 mo
2 mo
2 mo

Duration...
Congenital infection

Host Category

Mycobacterium
avium
complex

Immunocompetent

NONTUBERCULOUS MYCOBACTERIA†
Mycobacter...
Immunocompetent or
immunocompromised

All

All

Mycobacterium
kansasii

Mycobacterium
marinum

Host Category

Mycobacteriu...
All

All

Mycobacterium
fortuitum

Host Category

Mycobacterium
ulcerans

Pathogen

Duration

Comments

Catheter removal +...
Mycobacterium
chelonae

Mycobacterium
abscessus

Pathogen

Variable

Variable

[Tobramycin +
(meropenem or
linezolid) +
cl...
Cytomegalovirus

Pathogen

Neonate

Immunocompromised

Host Category

Ganciclovir, IV indefinitely

Long-term suppression
...
[Acyclovir PO or
Famciclovir PO or
Valacyclovir PO] for 7–10 days
or
Acyclovir IV for 5–7 days

Genital (first episode)

H...
Pathogen

Acyclovir IV (30 mg/kg/day
divided into 3 doses) for 7–14
days
Acyclovir PO for 7–14 days or
Famciclovir PO or
V...
Herpes simplex
(HSV)
(Coutinued)
Influenza A
and B

Pathogen

Indication

Keratoconjunctivitis

Treatment

Treatment

Host...
Indication

Acyclovir IV for 7–10 days

Acyclovir PO or IV for 7–10 days

Varicella

Zoster

Acyclovir PO or IV for 5–7 da...
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ANTIBIÓTICOS.
THE HARRIET LANE 2013
PEDIATRIA

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  1. 1. EgyptianPediatrics Yahoo Group http://health.groups.yahoo.com/group/ EgyptianPediatrics/
  2. 2. THE HARRIET LANE HANDBOOK OF PEDIATRIC ANTIMICROBIAL THERAPY
  3. 3. THE HARRIET LANE HANDBOOK OF PEDIATRIC ANTIMICROBIAL THERAPY Second Edition Julia A. McMillan, MD Professor of Pediatrics Associate Dean for Graduate Medical Education Johns Hopkins University School of Medicine Baltimore, Maryland Carlton K. K. Lee, PharmD, MPH Clinical Pharmacy Specialist, Pediatrics Program Director, Pediatric Pharmacy Residency Department of Pharmacy The Johns Hopkins Hospital; Associate Professor, Pediatrics Johns Hopkins University School of Medicine Baltimore, Maryland George K. Siberry, MD, MPH Assistant Professor Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, Maryland Karen C. Carroll, MD Director, Division of Medical Microbiology Director, Medical Microbiology Fellowship Program Professor of Pathology Johns Hopkins University School of Medicine Baltimore, Maryland
  4. 4. 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899 THE HARRIET LANE HANDBOOK OF PEDIATRIC ANTIMICROBIAL THERAPY, SECOND EDITION ISBN: 978-0-323-11247-5 Copyright © 2014 by Saunders, an imprint of Elsevier Inc. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). NOTICES Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous edition copyrighted 2009 Library of Congress Cataloging-in-Publication Data The Harriet Lane handbook of pediatric antimicrobial therapy / [edited by] Julia A. McMillan … [et al.].—2nd ed.     p. ; cm.   Handbook of pediatric antimicrobial therapy   Includes bibliographical references and index.   ISBN 978-0-323-11247-5 (pbk.)   I.  McMillan, Julia A.  II.  Johns Hopkins Hospital. Children’s Center.  III.  Title: Handbook of pediatric antimicrobial therapy.   [DNLM:  1.  Anti-Infective Agents—therapeutic use—Handbooks.  2.  Adolescent.  3.  Child.  4.  Infant. QV 39]   RM262   615′.1—dc23 2013003412 Content Strategist: James Merritt Content Development Specialist: Andrea Vosburgh Publishing Services Manager: Pat Joiner Design Manager: Steven Stave Printed in the United States of America Last digit is the print number:  9  8  7  6  5  4  3  2  1 W orking together to grow libraries in developing countries www.elsevier.com | www.bookaid.org | www.sabre.org
  5. 5. DEDICATION We dedicate this second edition of The Harriet Lane Handbook of Pediatric Antimicrobial Therapy to the clinicians and investigators whose work has allowed continued improvement in our ability to treat and to prevent infections in infants and children.
  6. 6. Contributors Karen C. Carroll, MD Director, Division of Medical Microbiology Director, Medical Microbiology Fellowship Program Professor of Pathology Johns Hopkins University School of Medicine Baltimore, Maryland Lisa A. Degnan, PharmD, BCPS Clinical Assistant Professor Ernst Mario School of Pharmacy Rutgers, The State University of New Jersey; Clinical Pharmacy Specialist, Pediatrics Hackensack University Medical Center Hackensack, New Jersey Swathi Gowtham, MD Clinical Fellow Division of Pediatric Infectious Diseases Division of Clinical Pharmacology Johns Hopkins University School of Medicine Baltimore, Maryland Angela M. Helder, PharmD, BCPS Clinical Pharmacy Specialist Pediatric Emergency Medicine Department of Pharmacy The Johns Hopkins Hospital Baltimore, Maryland Hiwot Hiruy, MD Clinical Fellow Division of Pediatric Infectious Diseases Johns Hopkins University School of Medicine Baltimore, Maryland Carlton K. K. Lee, PharmD, MPH Clinical Pharmacy Specialist, Pediatrics Program Director, Pediatric Pharmacy Residency Department of Pharmacy The Johns Hopkins Hospital; Associate Professor, Pediatrics Johns Hopkins University School of Medicine Baltimore, Maryland vii
  7. 7. viii    Contributors Melissa D. Makii, PharmD, BCPS Clinical Pharmacy Specialist Pediatric Oncology Department of Pharmacy Rainbow Babies and Children’s Hospital Cleveland, Ohio Julia A. McMillan, MD Professor of Pediatrics Associate Dean for Graduate Medical Education Johns Hopkins University School of Medicine Baltimore, Maryland Kristine A. Parbuoni, PharmD, BCPS Clinical Pharmacy Specialist Pediatric Critical Care University of Maryland Medical Center Baltimore, Maryland George K. Siberry, MD, MPH Assistant Professor Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, Maryland Elizabeth A. Sinclair, PharmD, BCPS Clinical Pharmacist Pediatric Critical Care Riley Hospital for Children at Indiana University Health Indianapolis, Indiana Paul K. Sue, MD Clinical Fellow Division of Pediatric Infectious Diseases Johns Hopkins University School of Medicine Baltimore, Maryland
  8. 8. Preface This second edition of The Harriet Lane Handbook of Pediatric Antimicrobial Therapy was, like the first edition, a collaboration that included the disciplines of pediatric infectious diseases, microbiology, and clinical pharmacology. We recognize that decisions regarding effective antimicrobial therapy require the knowledge and experience of all three of these disciplines, particularly when caring for children whose infections are complications of underlying conditions or the compromised immunity that results from chemotherapy or surgery. For this edition, our microbiology expert was Dr. Karen C. Carroll, who kindly agreed to replace Dr. James Dick, who is now retired. Dr. Carroll reviewed and significantly revised Chapter 4, Mechanisms of Action and Routes of Administration of Antimicrobial Agents, and Chapter 5, Mechanisms of Drug Resistance. The other faculty authors for the first edition have participated in this one, but the pediatric infectious diseases fellows, Drs. Hiwot Hiruy, Swathi Gowtham, and Paul K. Sue, all contributed for the first time. Their dedication to excellence in the care of their patients is reflected in the care with which they have reviewed and revised Chapter 2, Recommended Empiric Antimicrobial Therapy for Selected Clinical Syndromes. Because decision-making about antimicrobial selection and dosage requires more than matching a “drug” to a “bug,” we are particularly proud to that Dr. Carlton K. K. Lee was able to recruit former Pediatric Pharmacy residents Drs. Lisa A. Degnan, Angela M. Helder, Melissa D. Makii, Elizabeth A. Sinclair, and Kristine A. Parbuoni to assist in revising Chapter 3, Drug Dosing in Special Circumstances; Chapter 6, Therapeutic Drug Monitoring; Chapter 7, Adverse Drug Reactions; and Chapter 9, Antimicrobial Desensitization Protocols. We have reviewed available evidence and current guidelines from expert panels to provide recommendations that are as accurate and as contemporary as is possible. We realize, however, that new evidence and guidelines will emerge during the life of this second edition, so we urge readers to consult additional resources, particularly for unusual infections or for suspected antimicrobial resistance. ix
  9. 9. x    Preface Decisions regarding antimicrobial therapy for children require an understanding of biologic development, mechanisms of resistance, and pharmacology. We hope that this handbook will help clinicians in their efforts to provide the most effective therapy for each individual circumstance. Karen C. Carroll, MD Carlton K. K. Lee, PharmD, MPH Julia A. McMillan, MD George K. Siberry, MD, MPH Swathi Gowtham, MD Hiwot Hiruy, MD Paul K. Sue, MD Lisa A. Degnan, PharmD, BCPS Angela M. Helder, PharmD, BCPS Melissa D. Makii, PharmD, BCPS Kristine A. Parbuoni, PharmD, BCPS Elizabeth A. Sinclair, PharmD, BCPS
  10. 10. Notes and Abbreviations Used in Tables TABLE 1-1 *Some recommendations are for antibiotics that are not approved by the U.S. Food and Drug Administration (FDA) for use in children, and some may not be approved for treatment of the pathogen listed. Recommendations are based on published evidence of efficacy. A/C, Amoxicillin/clavulanic acid (Augmentin); AG, aminoglycoside; APCS, antipseudomonal cephalosporin; APPN, antipseudomonal penicillin; aq, aqueous; BL/BLI, β-lactam plus β-lactamase inhibitor combination; BT, bioterrorism; CDC, Centers for Disease Control and Prevention; Ceph, cephalosporin; 1st Ceph, first generation cephalosporin; 2nd Ceph, second generation cephalosporin; 3rd Ceph, third generation cephalosporin; CGD, chronic granulomatous disease; CHL, chloramphenicol; CNS, central nervous system; CSF, cerebrospinal fluid; EM, erythema marginatum; ESBL, extended-spectrum β-lactamase producer; FQ, fluoroquinolone; GI, gastrointestinal; HUS, hemolytic uremic syndrome; IM, intramuscular; IV, intravenous; IVIg, intravenous immunoglobulin; LP, lumbar puncture; MIC, minimum inhibitory concentration; NSAID, nonsteroidal anti-inflammatory drug; OCS, oral cephalosporin; OCS1, first generation oral cephalosporin; OCS2, second generation oral cephalosporin; OCS3, third generation oral cephalosporin; PCS, parenteral cephalosporin; PCS1, first generation parenteral cephalosporin; PCS2, second generation parenteral cephalosporin; PCS3, third generation parenteral cephalosporin; PCS4, fourth generation parenteral cephalosporin; PenG, penicillin G; Pen VK, penicillin VK (oral); PID, pelvic inflammatory disease; Pip/tazo, piperacillin/ tazobactam (Zosyn); PO, by mouth; PPI, proton pump inhibitor; R/O, rule out; RE, reticuloendothelial; SS-Pen, semisynthetic penicillin (nafcillin, oxacillin); Tic/clav, ticarcillin/clavulanic acid (Timentin); TMP/SMX, trimethoprim/sulfamethoxazole; UTI, urinary tract infection; WBC, white blood cell. TABLE 1-2 Some recommendations are for antibiotics that are not approved by the U.S. Food and Drug Administration for use in children, and some may not be approved for treatment of the pathogen listed. Recommendations are based on published evidence of efficacy. *Public health authorities should be notified if an individual has newly diagnosed latent infection. xiii
  11. 11. xiv    Notes and Abbreviations Used in Tables † Intramuscular streptomycin is usually recommended; if not available, kanamycin, amikacin, or capreomycin can be used. ‡ Recommendations are for presumptive therapy and no recommendation for duration is provided. Controlled trials are limited, and susceptibility testing may not correlate with clinical response. Guidance from a specialist in treating mycobacterial infection is recommended. § Doxycycline should be prescribed for children <8 years old only if the benefits outweigh the risks. ART, Antiretroviral therapy; DOT, directly observed therapy; TB, tuberculosis; TMP/SMX, trimethoprim-sulfamethoxazole; TST, tuberculin skin test. TABLE 1-3 Some recommendations are for antibiotics that are not approved by the U.S. Food and Drug Administration for use in children, and some may not be approved for treatment of the pathogen listed. Recommendations are based on published evidence of efficacy. CMV, Cytomegalovirus; CNS, central nervous system; GI, gastrointestinal; HSV, herpes simplex virus; IM, intramuscular; IV, intravenous; PO, by mouth. TABLE 1-4 Some recommendations are for antibiotics that are not approved by the U.S. Food and Drug Administration for use in children, and some may not be approved for treatment of the pathogen listed. Recommendations are based on published evidence of efficacy. *Recommendations for duration of treatment often cannot be provided because optimal duration depends on disease severity and immune status of the patient. † Unless a specific recommendation is made, decisions regarding the appropriate formulation of amphotericin B should be made based on a need to reduce toxicity associated with amphotericin B deoxycholate. Lipid complex and liposomal formulations are associated with fewer adverse events, but they do not enhance efficacy. Amphotericin B deoxycholate is the preferred formulation for treating neonates and other patients with renal involvement because lipid complex and liposomal forms do not achieve effective concentration in the kidneys. ‡ Candida albicans is generally susceptible to fluconazole; C. krusei is resistant to fluconazole; C. glabrata is often resistant to fluconazole but may be susceptible to high doses; C. lusitaniae may be resistant to amphotericin B. § Includes Absidia spp., Mucor spp., Rhizomucor spp., Rhizopus spp., Mortierella spp., Cunninghamella spp., Penicillium spp., Acremonium spp., and Fusarium spp.
  12. 12. Notes and Abbreviations Used in Tables    xv TABLE 1-6 Some recommendations are for antibiotics that are not approved by the U.S. Food and Drug Administration for use in children, and some may not be approved for treatment of the pathogen listed. Recommendations are based on published evidence of efficacy. a Available from Leiters Park Avenue Pharmacy, San Jose, CA (800-292-6773). b Approved drug but considered investigational for this indication. c Not recommended during pregnancy and for children younger than 8 yr. d Can be obtained from the CDC Drug Service (404-639-3670 or 404-639-2888 evenings and weekends). e Fumagillin is made by Mid-Continent Agrimarketing, Inc., Olathe, KS (800-547-1392). f Not available commercially. This drug can be compounded as a service by Medical Center Pharmacy, New Haven, CT (203-688-6816), or by Panorama Compounding Pharmacy, 6744 Balboa Blvd., Van Nuys, CA 91406 (800-247-9767). g Triclabendazole is available from Victoria Pharmacy, Zurich, Switzerland (41-1-211-24-32). h Available in limited supply from WHO. i Not marketed in the United States. j Not recommended in pregnant or breastfeeding women. k Miltefosine is manufactured by Paladin (Montreal, Quebec, Canada) and is not available in the United States. l Artemether/lumefantrine is contraindicated during the first trimester of pregnancy; safety during the second and third trimester has not been established. It should not be used in patients with cardiac arrhythmias, bradycardia, severe cardiac disease, or prolonged QT interval, and it should not be given concomitantly with drugs that prolong the QT interval or are metabolized by CYP2D6. m If quinidine is unavailable, call Eli Lilly (800-821-0538) or the CDC Malaria Hotline (770-488-7788). CDC, Centers for Disease Control and Prevention; CNS, central nervous system; FDA, U.S. Food and Drug Administration; GI, gastrointestinal; IM, intramuscular; IV, intravenous; LP, lumbar puncture; PO, by mouth; WHO, World Health Organization. TABLE 2-1 *Pharmacokinetics of Synercid (quinupristin plus dalfopristin) and daptomycin have not been studied, and use in children has been limited. † Spectinomycin is not available in the United States. ‡ Li PK, Szeto CC, Piraino B, et al. Peritoneal dialysis-related infections recommendations: 2010 update. Perit Dial Int 2010;30:393-423. A/C, Amoxicillin/clavulanic acid; AG, aminoglycoside; AP pen, antipseudomonal penicillin; BAL, bronchoalveolar lavage; BL/BLI,
  13. 13. xvi    Notes and Abbreviations Used in Tables β-lactam plus β-lactamase inhibitor; CGD, chronic granulomatous disease; CMV, cytomegalovirus; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; EBV, Epstein-Barr virus; FDA, U.S. Food and Drug Administration; FQ, fluoroquinolone; GAS, group A streptococcus; GBS, group B streptococcus; GI, gastrointestinal; GU, genitourinary; HSV, herpes simplex virus; IVIg, intravenous immunoglobulin; MRSA, methicillin-resistant Staphylococcus aureus; MRSE, methicillin-resistant Staphylococcus epidermidis; MSSA, methicillin-susceptible Staphylococcus aureus; NSAID, nonsteroidal anti-inflammatory drug; OCS2/3, second generation oral cephalosporin; OCS3, third generation oral cephalosporin; OM, otitis media; PCN, penicillin; PCR, polymerase chain reaction; PCS3, third generation parenteral cephalosporin; Pip/tazo, piperacillin/tazobactam; RFQ, respiratory fluoroquinolone (levofloxacin, moxifloxacin); RSV, respiratory syncytial virus; STI, sexually transmitted infection; TB, tuberculosis; Tic/clav, ticarcillin/clavulanic acid; TMP/SMX, trimethoprim/sulfamethoxazole; UTI, urinary tract infection. TABLE 3-1 *Pharmacogenomic polymorphisms should be taken under consideration for potential altered net effect. † Works cooperatively with transporters (e.g., MDR-1 or P-glycoprotein). ↑, Increased; ↓, decreased; ?, unknown; BSA, body surface area; CNS, central nervous system; GI, gastrointestinal. TABLE 3-3 *Route in parentheses indicates secondary route of excretion. † Subsequent doses are best determined by measurement of serum levels and assessment of renal insufficiency. ‡ May add to peritoneal dialysate to obtain adequate serum levels. § For a glomerular filtration rate (GFR) ≥5 mL/min, give full dose as first dose; for a GFR <5 mL/min, give 33% of full dose as first dose. ¶ May inactivate aminoglycosides in patients with renal impairment. ‖ Rate of acetylation of isoniazid. **If using high-flux hemodialysis (polysulfone polyamide and polyacrylonitrile), give supplemental dose after dialysis. ?, Unknown; CrCl, creatinine clearance; D, dose reduction; DI, dose reduction and interval extension; D,I, dose reduction or interval extension; He, hemodialysis; I, interval extension; N, no; N/A, not applicable; NRTI, nucleoside reverse transcriptase inhibitor; P, peritoneal dialysis; Y, yes. TABLE 3-4 CAVH, Continuous arteriovenous hemodialysis; CAVHD, continuous arteriovenous hemodialysis, CF, cystic fibrosis; CrCl, creatinine clearance
  14. 14. Notes and Abbreviations Used in Tables    xvii rate; CNS, central nervous system; CVVH, continuous venovenous hemofiltration; CVVHD, continuous venovenous hemodialysis; IV, intravenous; PCP, Pneumocystis pneumonia; PO, by mouth. TABLE 3-7 +, Use with caution in the presence of hepatic impairment; IM, intramuscular; INR, international normalized ratio; IV, intravenous. TABLE 3-8 ABW, Adjusted body weight (kg); ClCr, creatinine clearance (mL/min/1.73m2); CrCl, creatine clearance; IBW, ideal body weight (kg); MIC, minimum inhibitory concentration; TBW, total or actual body weight (kg); Vd, volume of distribution (L/kg). TABLE 3-9 +/−, Yes in some studies, no in others; BBB, blood–brain barrier; CNS, central nervous system; CSF, cerebrospinal fluid; IM, intramuscular; IV, intravenous; MIC, minimum inhibitory concentration; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. TABLE 4-1 *Unique among β-lactams; binds to PBP2a, so it has methicillin-resistant Staphylococcus aureus activity. † Ophthalmic drops or retinal administration. ‡ Vaginal cream. HBV, Hepatitis B virus; IM, intramuscular; INHAL, inhalation; IV, intravenous; mRNA, messenger RNA; PBP, penicillin-binding protein; PO, by mouth; rRNA, ribosomal RNA; T, topical; tRNA, transfer RNA. TABLE 6-1 *Assuming normal renal function. † Terminal half-life. ‡ These steady-state times are achieved regardless of whether a loading dose is administered. § Data for specific peak and trough levels and efficacy are not well established. Trough concentration at four to five times the minimum inhibitory concentration (MIC) has been recommended with higher concentrations; may be needed for sequestered infections or situations of poor vancomycin tissue penetration. ‖ Postconceptual age: the sum of gestational age at birth and chronologic age. ¶ Nonlinear pharmacokinetics exhibited in adults and children because of saturation of voriconazole metabolism and higher than proportional
  15. 15. xviii    Notes and Abbreviations Used in Tables increase in exposure observed with an increasing dose; however, linear pharmacokinetics has been reported in younger children. CNS, Central nervous system; IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus; N/A, not applicable; SSTI, skin and soft tissue infection. TABLE 6-2 *Reflects free-drug concentration measurements. AUC/MIC, Area under the serum concentration versus time curve to minimum inhibitory concentration ratio; Cmax    MIC, maximum serum / concentration to MIC ratio; T > MIC, duration of the dosing interval with serum concentrations exceeds the MIC; PD, pharmacodynamics; PK, pharmacokinetics. TABLE 6-3 AUC/MIC, Area under the serum concentration versus time curve to minimum inhibitory concentration ratio; PD, pharmacodynamics; PK, pharmacokinetics. TABLE 6-4 AUC/MIC, Area under the serum concentration versus time curve to minimum inhibitory concentration ratio; Cmax    MIC, maximum / serum concentration to MIC ratio; PD, pharmacodynamics; PK, pharmacokinetics. TABLE 6-5 *Postantifungal effects have been identified for certain drugs within the indicated antifungal drug class and specific Candida strain. AUC/MIC, Area under the serum concentration versus time curve to minimum inhibitory concentration ratio; Cmax    MIC, maximum serum / concentration to MIC ratio; T > MIC, duration of the dosing interval with serum concentrations exceeds the MIC; PD, pharmacodynamics; PK, pharmacokinetics. TABLE 8-1 CDC, Centers for Disease Control and Prevention; CMV, cytomegalovirus; CSF, cerebrospinal fluid; DTaP, diphtheria and tetanus toxoids and acellular pertussis vaccine; Ig, immunoglobulin; IM, intramuscular; IV, intravenous; IVIg, intravenous immunoglobulin; max, maximum; Td, adult-type diphtheria and tetanus toxoids vaccine; Tdap, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine; TMP/SMX, trimethoprim/sulfamethoxazole; TST, tuberculin skin test.
  16. 16. Notes and Abbreviations Used in Tables    xix TABLE 9-1 Observe patient for 30 min, then give full therapeutic dose by the desired route. *Interval between doses is 15 min. TABLE 9-2 Observe patient for 30 min, then give full therapeutic dose by the desired route. *Interval between doses is 15 min. TABLE 9-3 Observe patient for 30 min, then give full therapeutic dose by the desired route. *Interval between doses is 15 min. TABLE 9-4 *Interval between doses is 30 min. TABLE 9-5 Protocol for intravenous desensitization to all cephalosporins with a goal dose of 1 and 2 g. TABLE 9-6 Protocol for intravenous desensitization to all cephalosporins with a goal dose of 2 g. *Interval between doses is 15 min. TABLE 9-7 *Interval between doses is 30 min. Dose is expressed as sulfamethoxazole portion of trimethoprim/sulfamethoxazole (TMP/SMX). If an allergic reaction occurs, formal desensitization should be performed. NA, Not applicable. TABLE 9-10 Drink 180 mL water after each dose of trimethoprim/sulfamethoxazole (TMP/SMX). Subjects tolerating this protocol were prescribed 800/160 mg TMP/SMZ every Monday, Wednesday, and Friday for low-dose Pneumocystis jiroveci (carinii) prophylaxis. NA, Not applicable. TABLE 9-11 *Administer doses as continuous 15-min infusions, except for the last three doses, which are given as 30-min infusions with no intervals between the doses.
  17. 17. xx    Notes and Abbreviations Used in Tables TABLE 9-12 *Interval between doses is 15 min. NA, Not applicable. TABLE 9-14 *Beginning on day 7, doses infused consecutively. IV, Intravenously. TABLE 9-17 *Interval between doses is 8 hours. TABLE 9-18 *Goal interval between doses is 20 minutes. NA, Not applicable. TABLE 9-19 *Interval between doses is 30 minutes.
  18. 18. Chapter 1  Infectious Agents and Drugs of Choice Julia A. McMillan, MD, and George K. Siberry, MD, MPH 1
  19. 19. All All All Aggregatibacter actinomycetemcomitans (formerly Actinobacillus sp.) Actinomyces israeli and other species Host Category Acinetobacter spp. Pathogen Any Any Respiratory, bacteremia Indication/ Type of Infection IV PenG or Ampicillin, then oral amoxicillin 3rd ceph Imipenem Recommended Treatment 4–6 wk 6–12 mo Variable (endocarditis, 4–6 wk) ≥14 days (depending on site of infection) Duration Variable endocarditis, 4–6 wk Penicillin + gentamicin or Ampicillin + gentamicin or Ciprofloxacin PCS3 or PCS then Oral: Erythromycin, Doxycycline, or Clindamycin 3 wk 4 wk 6–12 mo ≥14 days (depending on site of infection) Duration Other carbapenem or Ampicillin/ sulbactam or Colistin or Tigecycline Alternative Treatment TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (for notes and abbreviations used in this table, see p. xiii.) I.  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS Surgical debridement. Prolonged antibiotics essential. Failure of erythromycin, doxycycline, or clindamycin may be caused by presence of Aggregatibacter. Variably but often highly resistant—susceptibility results guide final choice; colistin used in some highly resistant cases. Tigecycline and doripenem not FDA approved for <18 yr old. Common coinfection with Actinomyces. May add AG or rifampin to 3rd ceph for endocarditis. Comments 2    Chapter 1  Infectious Agents and Drugs of Choice
  20. 20. Any Disseminated Disseminated All All Pregnant Rifampin or Doxycycline Doxycycline Ceftazidime or Meropenem All: ≥7 days and 3 days afebrile ≥10 days (depending on site of infection) ≥7 days and 3 days afebrile ≥10 days (depending on site of infection) 3rd ceph + gentamicin Invasive Achromobacter xylosoxidans (formerly Alcaligenes xylosoxidans) Anaplasma phagocytophila (formerly Ehrlichia phagocytophila) 5 days? Duration TMP/SMX Recommended Treatment Gastroenteritis Indication/ Type of Infection All Host Category Aeromonas hydrophila Pathogen — Tetracycline or Rifampin Carbapenem or Tetracycline or Ciprofloxacin Other Carbapenem or TMP/SMX FQ or Tetracycline Alternative Treatment ≥10 days (depending on site of infection) ≥7 days and 3 days afebrile ≥10 days (depending on site of infection) 5 days? 5 days? Duration 1 Continued Limited clinical data about efficacy of rifampin vs. potential negative effect of doxycycline on bones and teeth of fetus. Variable activity of Pip/tazo, Tic/clav, FQ, ceftobiprole. Initial therapy guided by local susceptibility patterns. Doxycycline is drug of choice regardless of age. No evidence of teeth staining after ≤2-wk course of doxycycline. Chloramphenicol not recommended. Levofloxacin active in vitro. Debridement Unclear benefit of antimicrobial treatment. Comments Chapter 1  Infectious Agents and Drugs of Choice    3
  21. 21. All All All Bacillus anthracis (potential BT agent) Bacillus cereus Host Category Arcanobacterium haemolyticum Pathogen [Doxycycline or Ciprofloxacin] + [Rifampin and/or Clindamycin] None Vancomycin Gastrointestinal; pulmonary; invasive Invasive Food poisoning Doxycycline or Ciprofloxacin Variable 60 days All: 7–10 days (60 days if BT) 10 days? PenG +/− AG Invasive disease Cutaneous Unknown Duration Erythromycin Recommended Treatment Pharyngitis Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) Ciprofloxacin or Meropenem or Imipenem or Clindamycin [Levofloxacin or ofloxacin] + [Rifampin and/ or clindamycin] Clindamycin or Ceph or Macrolide Levofloxacin or Amoxicillin (see comments) or Penicillin (see comments) Clindamycin or Tetracycline or Penicillin Alternative Treatment Variable All: 7–10 days (60 days if BT) Variable Unknown Duration Debridement and hardware removal. Uniformly resistant to β-lactams. Supportive care only Potential BT agent. Cephalosporins and TMP/ SMX not reliable. Potential BT agent. Penicillin or amoxicillin can be used to complete therapy for children <8 yr old with naturally acquired anthrax or proven penicillin-susceptible after initial treatment with doxycycline or ciprofloxacin. AG may be warranted if endocarditis suspected. TMP/SMX resistant Test for penicillin susceptibility and tolerance. Comments 4    Chapter 1  Infectious Agents and Drugs of Choice
  22. 22. All Immunocompetent Bartonella henselae (cat scratch disease) Host Category Bacteroides: fragilis group Pathogen TMP/SMX and/or Rifampin and/or IV Gentamicin (see Comments) Severe systemic cat scratch disease Metronidazole Intracranial None or Azithromycin Metronidazole Below diaphragm Adenitis Clindamycin Recommended Treatment Above diaphragm Indication/ Type of Infection Rifampin or Ciprofloxacin or TMP/SMX Ciprofloxacin or Doxycycline All: ≥2 weeks? Carbapenem? Pip/tazo or Carbapenem or Cefoxitin Pip/tazo or Tic/clav or A/C or Ampicillin/ sulbactam or Carbapenem Alternative Treatment — 5 days Unknown Depends on site and ability to drain/débride Depends on site and ability to drain/débride Duration All: ≥2 weeks? 2–3/wk 2–3/wk 7–10 days Unknown Depends on site and ability to drain/débride Duration 1 Continued Preferred therapy unclear. Some experts advocate gentamicin until defervescence followed by TMP/SMX + rifampin for 2–4 weeks. (Florin et al. Pediatrics 2008).† Duration depends on clinical and radiologic response. Needle aspiration of suppurative lymph node for relief. Reserve antibiotic treatment for severe cases. Debridement/drainage important for therapy. Increasing clindamycin resistance. Debridement/drainage important for therapy. Comments Chapter 1  Infectious Agents and Drugs of Choice    5
  23. 23. All Bordetella pertussis, parapertussis Respiratory Erythromycin or Azithromycin or Clarithromycin Rifampin Chronic (Verruga peruana) All Erythromycin +/− rifampin or Doxycycline +/− rifampin CHL +/− Pen G or Ciprofloxacin +/− ceftriaxone Bacillary peliosis (liver, other RE sites) Bacillary angiomatosis Acute (Oroya fever) Immunocompromised Ceftriaxone + gentamicin +/− doxycycline Recommended Treatment Endocarditis Indication/ Type of Infection Any Host Category Bartonella bacilliformis (bartonellosis or Carrion’s disease) Bartonella henselae or quintana Pathogen TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 14 days 5 days 7 days 14–21 days 10 days after fever resolves 2–3 mo (angiomatosis) 4 mo (peliosis) Prolonged Duration Azithromycin or Erythromycin or Ciprofloxacin TMP/SMX Doxycycline Azithromycin +/− rifampin Doxycycline + gentamicin Alternative Treatment 7–14 days 7–14 days 7–14 days 14 days Unknown 2–3 mo (angiomatosis) 4 mo (peliosis) Prolonged Duration Seen in the Andes mountains. Unclear benefit of treatment. Surgery. Increased pyloric stenosis with erythromycin use <2 wk old; not studied for other macrolides. Azithromycin preferred for infants <1 mo old. Seen in the Andes mountains. Chloramphenicol or ciprofloxacin preferred for prevention of secondary salmonellosis. Use second agent for severe or nonresponsive illness. Gentamicin for at least 14 days based on adult studies. Comments 6    Chapter 1  Infectious Agents and Drugs of Choice
  24. 24. Borrelia burgdorferi Pathogen Doxycycline or Amoxicillin Doxycycline Doxycycline Doxycycline Repeat initial prescription or Ceftriaxone Early localized disease/EM Multiple EM Isolated facial palsy Arthritis—initial Arthritis— recurrent or persistent Nonpregnancy, ≥8 yr old Recommended Treatment Indication/ Type of Infection Host Category 14–28 days 28 days 28 days 14–21 days 21 days 14–21 days Duration Penicillin IV or Cefotaxime Amoxicillin or Cefuroxime or Erythromycin Amoxicillin or Cefuroxime or Erythromycin Amoxicillin or Cefuroxime or Erythromycin Amoxicillin or Cefuroxime or Erythromycin Alternative Treatment 14–28 days 14–28 days 28 days 28 days 28 days 14–21 days 14–21 days 14–21 days 21 days 21 days 21 days 14–21 days 14–21 days 14–21 days Duration 1 Continued No clear option for patients intolerant of penicillin and ceftriaxone. Amoxicillin preferred alternative. Amoxicillin preferred alternative. Antibiotic treatment prevents late disease but has no impact on facial palsy outcome. Steroids not helpful. Amoxicillin preferred alternative. Amoxicillin preferred alternative. Comments Chapter 1  Infectious Agents and Drugs of Choice    7
  25. 25. Pathogen Borrelia burgdorferi (Continued) Amoxicillin Repeat initial prescription or Ceftriaxone Arthritis—initial Arthritis— recurrent or persistent Ceftriaxone or Penicillin IV Amoxicillin Isolated facial palsy Ceftriaxone or Cefotaxime Ceftriaxone Carditis Amoxicillin Multiple EM All Amoxicillin Early localized disease/EM Child <8 yr old, or pregnancy Recommended Treatment Indication/ Type of Infection Host Category TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) Meningitis or encephalitis Encephalitis, other late neurologic complications 14–28 days 14–28 days 14–28 days 14–21 days 14–28 days 14–28 days 28 days 28 days 14–21 days 21 days 14–21 days Duration Penicillin IV or Cefotaxime Penicillin IV or Doxycycline Penicillin IV or Cefotaxime Cefuroxime or Erythromycin Cefuroxime or Erythromycin Cefuroxime or Erythromycin Cefuroxime or Erythromycin Alternative Treatment 14–28 days 14–28 days 14–28 days 14–28 days 14–28 days 14–28 days 28 days 28 days 14–21 days 14–21 days 21 days 14–21 days 14–21 days Duration Repeated or prolonged antibiotic course not helpful. Doxycycline alternative only for patients ≥8 yr old, nonpregnant. If asymptomatic, alternative would be same oral regimen as for early disease. No clear option for patients intolerant of penicillin and ceftriaxone. NSAIDs helpful adjunctive therapy. Antibiotic treatment prevents late disease but has no impact on facial palsy outcome. Steroids not helpful. Comments 8    Chapter 1  Infectious Agents and Drugs of Choice
  26. 26. <8 yr old, or pregnant TMP/SMX + rifampin + gentamicin Doxycycline + rifampin + gentamicin Meningitis or endocarditis 4–6 mo 4–6 mo 2 wk 4–6 mo 4–6 mo 2 wk 6 wk 6 wk 6 wk 6 wk Doxycycline + rifampin Nonpregnant, ≥8 yr old Brucellosis 5–10 days 5–10 days 5–10 days Single dose Single dose Single dose Duration Doxycycline Penicillin or Erythromycin Doxycycline Penicillin or Erythromycin Recommended Treatment TMP/SMX + rifampin Brucella abortus and other species Relapsing fever—tickborne Relapsing fever—louseborne Indication/ Type of Infection <8 yr old, or pregnant Nonpregnant, ≥8 yr old Nonpregnant, ≥8 yr old Borrelia hermsii and turicatae <8 yr old, or pregnant Host Category Nonpregnant, ≥8 yr old <8 yr old, or pregnant Borrelia recurrentis Pathogen Doxycycline + rifampin + gentamicin — TMP/SMX + gentamicin Erythromycin or Penicillin Doxycycline + gentamicin or TMP/SMX + rifampin Penicillin or Erythromycin CHL Chloramphenicol Alternative Treatment 4–6 mo 4–6 mo 2 wk 4–8 wk 2 wk 5–10 days 5–10 days 6 wk 2 wk 6 wk 6 wk Single dose Single dose 5–10 days Single dose Duration 1 Continued Monitor for Jarisch–Herxheimer reaction. Comments Chapter 1  Infectious Agents and Drugs of Choice    9
  27. 27. All Southeast Asia, Australia, India, Central America Children Burkholderia mallei (potential BT agent) Burkholderia pseudomallei (potential BT agent) Campylobacter jejuni Adults All Host Category Burkholderia cepacia Pathogen Gastroenteritis Melioidosis Glanders Any Indication/ Type of Infection Azithromycin Erythromycin or Azithromycin Ceftazidime or Meropenem Followed by oral: doxycycline or TMP/SMX Sulfadiazine Meropenem Recommended Treatment TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 5 days 5–7 days 5 days 4–6 mo 4–6 mo 10–14 days 10–14 days Unknown 14 days? Duration Erythromycin or Ciprofloxacin or Doxycycline TMP/SMX or Imipenem or Minocycline or Ceftazidime or Quinolones or Chloramphenicol Doxycycline or FQ or Tobramycin or Gentamicin or Imipenem or Ceftazidime or TMP/SMX Parenteral phase: imipenem or CHL Oral phase: Amox/clav Doxycycline (≥8 yr old) Alternative Treatment 5–7 days 5–7 days 5–7 days 4–6 mo 5–7 days 10–14 days 10–14 days Unknown 14 days? (all) Duration FQ resistance is increasing. After IV therapy, give prolonged oral therapy. Combination therapy with meropenem + 1 or 2 agents from alternative list (e.g., meropenem + TMP/SMX may be needed for multiresistant strains). Limited clinical evidence for treatment recommendations. Comments 10    Chapter 1  Infectious Agents and Drugs of Choice
  28. 28. Chlamydophila (Chlamydia) pneumoniae Any Pneumonia All Capnocytophaga ochracea Any Invasive Indication/ Type of Infection Pneumonia <8 yr old All Capnocytophaga canimorsus Cardiobacterium hominis All Host Category All Campylobacter spp. Pathogen ≥8 yr old Doxycycline or Azithromycin Azithromycin 3rd ceph Clindamycin or A/C Carbapenem and/or Gentamicin Penicillin or A/C Recommended Treatment 14 days 5 days 5 days Variable Variable Variable Variable Duration Erythromycin or FQ or Clarithromycin Erythromycin or Clarithromycin Carbapenem or Pip/tazo or FQ Penicillin + gentamicin Pip/tazo or Clindamycin or Erythromycin 3rd ceph Alternative Treatment 10–21 days 10 days 10 days 10–21 days 10 days Variable Variable Variable Variable Duration 1 Continued Penicillin/gentamicin only if penicillin susceptibility confirmed. Dog oral flora. Consider splenic dysfunction. Susceptible to penicillin but may prefer A/C for coinfection with other dog oral flora. Human oral flora. Comments Chapter 1  Infectious Agents and Drugs of Choice    11
  29. 29. Chlamydia trachomatis Chlamydophila (Chlamydia) psittaci Pathogen Urethritis, cervicitis, proctitis PID Epididymitis All All All Psittacosis ≥8 yr old Conjunctivitis or pneumonia Psittacosis <8 yr old Infant Indication/ Type of Infection Host Category Doxycycline Doxycycline or Azithromycin Erythromycin or Azithromycin Doxycycline Azithromycin or Erythromycin Recommended Treatment TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 10 days 7 days 1 dose (1 g) 14 days 3–5 days 10–14 days after fever resolved Duration Erythromycin or Ofloxacin or Levofloxacin Erythromycin or Azithromycin or Clarithromycin Sulfonamide (oral) Clarithromycin Alternative Treatment 7 days 7 days 7 days 14 days? 10–14 days after fever resolved Duration See PID treatment recommendations in Chapter 2 (includes recommendations for C. trachomatis). 6 mo to 12 yr: erythromycin or azithromycin. Pregnancy: erythromycin, azithromycin, or amoxicillin. Increased risk for pyloric stenosis with erythromycin in infants <6 wk old. Sulfonamide for conjunctivitis, not pneumonia. Avoid sulfonamides in infants <4 wk old. Comments 12    Chapter 1  Infectious Agents and Drugs of Choice
  30. 30. All All Infant Citrobacter spp. Clostridium botulinum Host Category Chromobacterium violaceum Pathogen Variable 2–3 wk 4 wk to several mo 4 wk to several mo Duration Infant botulism See Comments Imipenem See Comments Meropenem or [PCS3 + aminoglycoside] Human-derived botulism immunoglobulin intravenous (BabyBIG) as soon as possible; ordering info at http://www.infantbotulism.org/ or 510-231-7600 OCS3 or Pip/tazo or FQ Initial phase: [CHL + Gentamicin] Oral phase: Doxycycline or CHL Alternative Treatment CNS, other serious infections Variable (all) 2–3 wk 2–3 wk 2–3 wk 4 wk to several mo Duration Carbapenem or [PCS3 +/− gentamicin] Initial phase: [TMP/SMX or FQ or Imipenem] then Oral phase: TMP/ SMX Recommended Treatment Non-CNS and other less serious infections Any Indication/ Type of Infection Comments 1 Continued Non-CNS infections: 10–14 days. CNS infections: ≥21 days; ≥4–6 wk if abscesses. Do not use antibiotics, especially aminoglycosides! BabyBIG active against botulinum toxin types A and B. R/O CGD. Erythromycin resistant, even if appears susceptible in vitro. Preferred treatment not well established. Two- to 3-wk initial phase (parenteral) followed by prolonged oral phase. Two drugs from list used by some for first 2–3 wk. Relapse common. PCS3 (ceftriaxone) alone preferred for C. koseri; resistance more common for C. freundii (ampC β-lactamase producer). Chapter 1  Infectious Agents and Drugs of Choice    13
  31. 31. All All All All Clostridium difficile Clostridium tetani Clostridium perfringens, other species Host Category Clostridium botulinum (Coutinued) Pathogen Duration Alternative Treatment Duration None (supportive) PenG + clindamycin + surgery Septicemia, necrotizing myositis/fasciitis Metronidazole + antitoxin Variable 10–14 days [Clindamycin or Metronidazole or Carbapenem] + surgery PenG IV + antitoxin Variable 10–14 days Equine-derived heptavalent (HBAT) botulinum antitoxin from local health department or CDC. [If local health department unavailable, contact CDC at 800-232-4636 or http://emergency.cdc.gov/agent/botulism/clinicians/ index.asp 10 days Oral vancomycin 10 days Oral metronidazole or IV metronidazole 10 days Recommended Treatment Food poisoning (perfringens) Tetanus Colitis Wound or foodborne botulism Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) Comments Surgery essential. Hyperbaric oxygen may be helpful. Stop other antibiotics. Limited data for nitazoxanide. Fidaxomicin an option for adults, but no data available for children. Positive toxin in infant may not signify disease. Human tetanus immunoglobulin (TIG) 3000–6000 units IM. Some experts infiltrate part of TIG into wound. HBAT active against all botulinum toxin types (A–F). 14    Chapter 1  Infectious Agents and Drugs of Choice
  32. 32. All All Corynebacterium jeikeium, other species Host Category Corynebacterium diphtheriae Pathogen Any Any Indication/ Type of Infection Vancomycin Antitoxin + [erythromycin or PenG aq or PenG procaine] Recommended Treatment Variable Antibiotic: 14 days Duration [Pen + AG] or Clindamycin or Erythromycin Alternative Treatment Variable Duration 1 Continued Before IV antitoxin is given, a scratch test with 1 : 1000 dilution of antitoxin in saline solution should be performed, followed by an intradermal test if the scratch test is negative. Dose of antitoxin depends on severity of clinical presentation. Desensitization required if patient sensitive. Antitoxin and specific instructions available from the CDC (770-488-7100 or http://www.cdc.gov/vaccines/ vpd-vac/diphtheria/dat/ dat-main.htm#how). Document eradication by 2 consecutive negative cultures at least 24 hr after beginning treatment. Repeat erythromycin if culture is positive. Use vancomycin until specific susceptibilities are known. Comments Chapter 1  Infectious Agents and Drugs of Choice    15
  33. 33. All All All All All Edwardsiella tarda Ehrlichia chaffeensis and Ehrlichia ewingii Eikenella corrodens Elizabethkingia (formerly Chryseobacterium) meningosepticum Host Category Coxiella burnetii Pathogen Health care–associated invasive 7–10 days (all) Unknown Vancomycin + rifampin ≥10–14 days 5–10 days and afebrile ≥3 days Ampicillin or Penicillin or A/C PCS3 Doxycycline Invasive Any Any None ≥18 mo Doxycycline + hydrochloroquine Endocarditis Gastroenteritis 10–14 days Duration Doxycycline Recommended Treatment Q fever Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) [TMP/SMX or Levofloxacin or Minocycline] + rifampin Ureidopenicillin or TMP/SMX or 3rd ceph or Carbapenem FQ Rifampin (pregnancy only) [Doxycycline or Ofloxacin] + rifampin FQ or TMP/SMX Alternative Treatment Unknown 7–10 days (all) ≥10–14 days 5–10 days and afebrile ≥3 days 3 yr 10–14 days 10–14 days Duration Doxycycline is drug of choice even in children <8 yr old. Consider alternative only for pregnant women. A/C better than penicillin or ampicillin for occasional strain that produces β-lactamase. All resistant to clindamycin and metronidazole. Formerly Flavobacterium; susceptibility testing may be unreliable. Similar to Salmonella. More common in warm climates. May not need treatment in mild illness; TMP/SMX in pregnancy. Comments 16    Chapter 1  Infectious Agents and Drugs of Choice
  34. 34. All All All All Enterococcus faecalis and faecium (not vancomycin resistant) Enterococcus, vancomycin resistant (VRE) (usually E. faecium) Erysipelothrix rhusiopathiae Host Category Enterobacter spp. Pathogen Linezolid or Daptomycin Sepsis, meningitis endocarditis, other invasive infection Sepsis or Endocarditis PenG or Ampicillin Linezolid or Quinupristin/ dalfopristin Quinupristin/ dalfopristin ≥2 wk (sepsis) 2–3 wk (CNS) 8–12 wk? (endocarditis) 4–6 wk 4–6 wk PCS3 or FQ or Imipenem Nitrofurantoin or FQ (if susceptible) Vancomycin + gentamicin Carbapenem or FQ or Tic/clav or Pip/tazo or [PCS3 + AG] Vancomycin Alternative Treatment 7–14 days 7–14 days ≥2 wk (sepsis) 2–3 wk (CNS) 4–6 wk (endocarditis) Ampicillin + gentamicin or Penicillin + gentamicin Sepsis, meningitis, endocarditis Urinary tract 7–14 days 7–14 days ≥10–14 days Duration Ampicillin or Nitrofurantoin Ureidopenicillin + aminoglycoside Recommended Treatment Urinary tract Any Indication/ Type of Infection ≥2 wk (sepsis) 2–3 wk (CNS) 8–12 wk? (endocarditis) 4–6 wk 4–6 wk 4–6 wk 7–14 days 7–14 days ≥2 wk (sepsis) 2–3 wk (CNS) 4–6 wk (endocarditis) 7–14 days ≥10–14 days Duration 1 Quinupristin/dalfopristin not active against E. faecalis. Expect higher relapse rate for endocarditis. Oral antibiotics and shorter course for erysipeloid. Intrinsic vancomycin resistance. Continued Low-dose gentamicin for synergy. No gentamicin if high-level resistance, in which case, longer course (8–12 wk for endocarditis). Most VRE are E. faecium. Quinupristin/dalfopristin not active against E. faecalis. Nosocomial strains may be multiresistant. Laboratory should test for ESBL. Consider meropenem for CNS infection. Comments Chapter 1  Infectious Agents and Drugs of Choice    17
  35. 35. Escherichia coli Pathogen All Host Category PCS3 PCS3 Amoxicillin or TMP/SMX PCS 3 or OCS3 Sepsis Cystitis Pyelonephritis Recommended Treatment Meningitis Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 14 days 14 days 7–10 days 7–10 days 7–10 days 7–14 days 14 days 14 days 14 days 14 days Ampicillin + gentamicin or FQ or TMP/SMX or Gentamicin or BL/BLI ≥14 days ≥21 days ≥21 days Duration Sulfisoxazole or Nitrofurantoin or Oral ceph FQ or Pip/Tazo or Carbapenem ≥14 days 7–10 days 7–10 days Meropenem or Cefepime Alternative Treatment ≥21 days Duration Transition to oral antibiotics to complete 14-day course. Many oral options, based on susceptibility, including amoxicillin. Shorter courses of 3–5 days appropriate for adolescents and adults. Carbapenem if ESBL suspected. Treat for at least 21 days and at least 14 days from first negative CSF culture. Meropenem preferred if ESBL suspected. Comments 18    Chapter 1  Infectious Agents and Drugs of Choice
  36. 36. Escherichia coli— enterohemorrhagic (STEC) Escherichia coli— enteroinvasive Escherichia coli— enterotoxigenic Francisella tularensis Pathogen 10 days (longer if more severe illness) ≥10–14 days Gentamicin CHL + [streptomycin or gentamicin] Tularemia Tularemia with meningitis All Azithromycin 5 days Traveler’s diarrhea 5 days All Azithromycin Dysentery For all: 7 days All None PCS3 or BL/BLI Intra-abdominal Duration Diarrhea (risk for HUS) Recommended Treatment Indication/ Type of Infection All Host Category Doxycycline + [streptomycin or gentamicin] Streptomycin or Ciprofloxacin or CHL FQ FQ Carbapenem or FQ or Cefoxitin Alternative Treatment ≥14 days All: 10 days (longer if more severe illness) 3 days 3 days For all: 7 days Duration 1 Continued Recommendations based on few cases. More relapses with tetracyclines. 3rd ceph poor despite in vitro susceptibility. TMP/SMX resistance common. Carbapenem if ESBL suspected. If polymicrobial (gut flora) infection likely, add metronidazole to PCS3 or FQ to improve anaerobic coverage. Seven days adequate provided signs of infection have resolved (i.e., afebrile, normal WBC counts, oral intake resumed.) (Infectious Diseases Society of America Clinical Practice Guidelines: Clin Infect Dis 2010; 50:625–663) Antibiotic therapy has no proven benefit and may increase risk for HUS. TMP/SMX resistance common. Comments Chapter 1  Infectious Agents and Drugs of Choice    19
  37. 37. Haemophilus influenzae—type b, occasionally other types, rarely nontypeable Gardnerella vaginalis (see Bacterial Vaginosis in Chapter 2) Haemophilus ducreyi Fusobacterium spp. Pathogen All All Host Category Other invasive, non-CNS Meningitis Chancroid Bacteremia (septic jugular vein thrombosis/ Lemierre syndrome) Indication/ Type of Infection PCS3 or Ampicillin/ sulbactam IV Ceftriaxone or Azithromycin Ceftriaxone or Cefotaxime Pip/tazo or Ticarcillin/clav or Meropenem or Imipenem Recommended Treatment TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 10 days 10 days 1 dose 1 dose 10 days 10 days 4–6 wk 4–6 wk 4–6 wk 4–6 wk Duration PCS2 or FQ IV Ciprofloxacin or Erythromycin Clindamycin IV or Metronidazole IV Alternative Treatment 10 days 10 days 3 days 7 days 4–6 wk 4–6 wk Duration Can switch IV to PO if ≥14 days, stable and good response. Role of anticoagulation unclear. Penicillin or other agents often used with metronidazole because co-infection with microaerophilic oral flora common. Comments 20    Chapter 1  Infectious Agents and Drugs of Choice
  38. 38. All Gastritis, gastric, and duodenal ulcers Endocarditis All Helicobacter pylori Conjunctivitis All Haemophilus influenzae—aegyptius, other nontypeable Haemophilus parainfluenza, haemolyticus, aphrophilus, other species Indication/ Type of Infection Otitis, otitisconjunctivitis, sinusitis Host Category Haemophilus influenzae— nontypeable Pathogen 14 days Amoxicillin + [clarithromycin or metronidazole] + PPI or Amoxicillin + metronidazole + bismuth 14 days 4 wk 5–10 days 5–10 days 10 days Duration Ceftriaxone FQ ophthalmic or Polymyxin/TMP A/C Recommended Treatment 10 days 1 dose 5–10 days 5–10 days 10 days 10 days 5 days 10 days Duration Ampicillin + 4 wk gentamicin or Ampicillin/ sulbactam + gentamicin Amoxicillin + PPI 5 days each for followed by initial and clarithromycin follow-on + PPI + regimen [metronidazole or tinidazole] OCS2 or OCS3 or Azithromycin or Clarithromycin or FQ or Ceftriaxone Gentamicin or Tobramycin Alternative Treatment 1 Continued Use ampicillin/sulbactam/ gentamicin instead of ampicillin + gentamicin for β-lactamase producers. H. aphrophilus renamed Aggregatibacter aphrophilus. PPI options include omeprazole, lansoprazole, esomeprazole, pantoprazole, rabeprazole. Increasing clarithromycin resistance. Some experts treat for only 5 days in children ≥6 yr old. Comments Chapter 1  Infectious Agents and Drugs of Choice    21
  39. 39. All All Klebsiella spp. Host Category Kingella kingae, other species Pathogen 7–14 days 7–14 days ≥21 days PCS3 or FQ PCS3 +/− AG Meningitis ≥28 days 3–5 days 3–5 days Pyelonephritis, bacteremia, sepsis (NO CNS) Cystitis, other minor infections ≥28 days *PenG + gentamicin or *Ampicillin + gentamicin or Ceftriaxone OCS 1/2/3 or A/C Endocarditis ≥28 days ≥14 days ≥14 days ≥14 days Duration PCS 1/2/3 or PenG or BL/BLI Recommended Treatment Osteomyelitis, arthritis Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) FQ Meropenem Pip/Tazo Gentamicin Carbapenem BL/BLI Ampicillin/ sulbactam + gentamicin or Other BL/BLI + gentamicin TMP/SMX or FQ AG or FQ or TMP/SMX or Oxacillin Alternative Treatment ≥21 days ≥21 days ≥21 days ≥14 days ≥14 days ≥14 days 7–10 days 7–10 days ≥28 days ≥28 days ≥14 days ≥14 days ≥14 days ≥14 days Duration Course 4–7 weeks. PenG or ampicillin only if no β-lactamase. For regimens with gentamicin, use gentamicin for whole course. For ESBL-positive strains, carbapenem drug of choice. Can use FQ if susceptible in vitro. Failure of BL/BLI (e.g., Pip/tazo) for ESBL-positive strains despite in vitro susceptibility. Meningitis: CSF cultures may be positive up to 2 wk despite treatment. Treat CNS infection ≥21 days and ≥10–14 days from first negative CSF culture. 2–3 weeks for arthritis; 3–6 weeks for osteomyelitis. PenG drug of choice if no β-lactamase. Vancomycin resistance uniform; clindamycin resistance common. Comments 22    Chapter 1  Infectious Agents and Drugs of Choice
  40. 40. Leptospira spp. (Leptospirosis) Legionella pneumophila Klebsiella (formerly Calymmatobacterium) granulomatis Pathogen Immunocompromised and/or severe illness All Healthy Pregnant Nonpregnant Host Category Amoxicillin or Doxycycline PenG Hospitalized or severe illness FQ Mild illness Mild to moderate illness Erythromycin or Azithromycin Azithromycin or FQ Doxycycline Carbapenem ESBL-positive Granuloma inguinale; donovanosis Recommended Treatment Indication/ Type of Infection 14 days 7–14 days 7–14 days ≥14–21 days ≥3 wk ≥3 wk 5–10 days 14–21 days As above for type of infection ≥3 wk Duration Doxycycline or Ceftriaxone or Cefotaxime Azithromycin Azithromycin Doxycycline or TMP/SMX or Erythromycin — TMP/SMX or Ciprofloxacin Erythromycin or Azithromycin (weekly) FQ Alternative Treatment 14 days 14 days 14 days 5 days ≥10 days 14–21 days 14–21 days 14–21 days As above for type of infection ≥3 wk ≥3 wk ≥3 wk ≥3 wk Duration 1 Continued Jarisch–Herxheimer reaction common after therapy initiation. Should have response within 7 days; if not, add gentamicin. Comments Chapter 1  Infectious Agents and Drugs of Choice    23
  41. 41. All Morganella Sepsis, pneumonia Older 14 days Ampicillin + gentamicin Variable Variable ≥10 days ≥10 days ≥10 days OCS3 or FQ PCS4 + AG or FQ or Carbapenem Invasive and/or severe illness All: variable 14–21 days Ampicillin + gentamicin A/C or TMP/SMX or OCS2,3 ≥21 days Duration Variable Variable Ampicillin + gentamicin Recommended Treatment PenG +/− AG or Ampicillin Cystitis; other less serious infections Noninvasive Non-CNS Neonatal All Meningitis Indication/ Type of Infection Any Any Host Category All Moraxella catarrhalis Listeria monocytogenes Pathogen Leuconostoc spp. TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) TMP/SMX or Pip/tazo Azithromycin or Clarithromycin or FQ or Doxycycline TMP/SMX TMP/SMX TMP/SMX Alternative Treatment Macrolide or Tetracycline or Clindamycin ≥10 days ≥10 days 7–10 days for UTI; others, variable All: variable 14 days ≥21 days Duration All: variable PCS3 can select spontaneous AmpC-derepressed mutants during therapy and lead to treatment failure. Comments Intrinsic vancomycin resistance. High rates of resistance to FQ and quinupristin/dalfopristin. Intrinsic ceph resistance. No good alternative for neonates and late pregnancy. Failures reported with vancomycin and CHL; FQ and linezolid—minimal clinical data. Duration depends on site of infection: for example, shorter for otitis media than for sinusitis. Duration depends on site of infection. 24    Chapter 1  Infectious Agents and Drugs of Choice
  42. 42. Host Category Indication/ Type of Infection All All Mycoplasma pneumoniae Neisseria gonorrhoeae Urethritis, pharyngitis, proctitis, epididymitis Lower respiratory tract infection Mycobacterium TB and others—Table 1.2 of this chapter Mycoplasma hominis All Any Pathogen Once Ceftriaxone + azithromycin or Ceftriaxone once + doxycycline 7 days 5 days ≥10 days ≥10 days Duration Azithromycin Doxycycline or Clindamycin Recommended Treatment Doxycycline or Erythromycin or Clarithromycin or FQ Cefixime + azithromycin or Cefixime + doxycycline High-dose azithromycin (2 g) FQ Alternative Treatment Once 7 days Once 7–10 days 7–10 days 7–10 days 7–10 days ≥10 days Duration 1 Continued Duration depends on site of infection. M. hominis is intrinsically resistant to macrolides. IVIG has been suggested for agammaglobulinemic patients. Best response if started within first 3–4 days of illness. Appropriate therapy for extrapulmonary disease not well defined. Ceftriaxone dose always 250 mg. Ceftriaxone strongly preferred. If alternative regimen used, patient should have test of cure 1 week after treatment. Fluoroquinolones not recommended unless susceptibility of infecting strain is documented. Comments Chapter 1  Infectious Agents and Drugs of Choice    25
  43. 43. Neisseria meningitidis Neisseria gonorrhoeae (Coutinued) Pathogen All Host Category Ceftriaxone Ceftriaxone PenG or PCS 3 Endocarditis Exposed infant Meningitis, sepsis, pneumonia Ampicillin or Meropenem or CHL — ≥4 wk Once 5–7 days 5–7 days Cefotaxime 10–14 days 5–7 days 5–7 days 5–7 days 10–14 days 7 days Ceftriaxone Cefotaxime Meningitis 7 days Ceftriaxone Disseminated, arthritis Once Duration See PID treatment recommendations in Chapter 2 (includes treatment for gonorrhea) Cefotaxime Alternative Treatment PID Once Duration Ceftriaxone Recommended Treatment Conjunctivitis Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) Some experts use PCS3 until susceptibilities known because of increasing penicillin resistance in some areas (especially Spain). CHL or meropenem only if very severe β-lactam allergy. 125 mg IM in term infant; 25–50 mg/kg (maximum 125 mg) IM in preterm infant. Cefotaxime may be preferred in newborns with increased bilirubin levels. Test and/or treat for C. trachomatis. Add treatment for C. trachomatis. Cefotaxime for neonates with hyperbilirubinemia or if neonate receiving IV calcium. Plus local irrigation. Add treatment for C. trachomatis. Comments 26    Chapter 1  Infectious Agents and Drugs of Choice
  44. 44. Pasteurella multocida Nocardia brasiliensis, asteroides, other species Pathogen PenG or Ampicillin Invasive or severe ≥6–12 mo 1–3 mo 1–3 mo TMP/SMX + Amikacin + Ceftriaxone 10–14 days 10–14 days 7–10 days 7–10 days ≥6–12 mo TMP/SMX + imipenem PenVK or Amoxicillin CNS or severe All 6–12 wk Duration TMP/SMX Recommended Treatment Localized Invasive Immunocompromised All Noninvasive Indication/ Type of Infection Normal Host Category PCS2 or FQ or Doxycycline [TMP/SMX + imipenem + amikacin] or [Imipenem + amikacin + ceftriaxone] Azithromycin or TMP/SMX or OCS2 or Doxycycline or FQ [Amikacin + imipenem] or [Amikacin + ceftriaxone] or [Amikacin + TMP/SMX] Minocycline or A/C Alternative Treatment 10–14 days 10–14 days 10–14 days ≥6–12 mo 1–3 mo 1–3 mo ≥6–12 mo ≥1–3 mo 1–3 mo 5 days 10–14 days 10–14 days 10–14 days 10–14 days ≥6–12 mo 6–12 wk 6–12 wk Duration 1 Continued PCS3 susceptible in vitro but clinical data lacking. Linezolid also active. Comments Chapter 1  Infectious Agents and Drugs of Choice    27
  45. 45. All Duration Clindamycin Metronidazole GI, genitourinary PCS3 Carbapenem Pip/tazo or Ampicillin/ sulbactam or Ticar/clav Clindamycin or Cefoxitin or Carbapenem or BL/BLI ≥10 days ≥10 days A/C or CS2/3 or Carbapenem Other β-lactam or Erythromycin or Minocycline or Imipenem or Clindamycin or Daptomycin Alternative Treatment Variable 3 days 3 days PenG +/− AG TMP/SMX or FQ Variable Recommended Treatment Oral, respiratory Invasive All Prevotella spp. Diarrhea All Plesiomonas shigelloides Any Indication/ Type of Infection All Host Category Pediococcus spp. Pathogen TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) ≥10 days ≥10 days ≥10 days ≥10 days ≥10 days ≥10 days ≥10 days Variable 3 days 3 days 3 days Variable Duration Longer duration if undrainable abscesses. Definitive antibiotic therapy should be guided by susceptibility testing. β-lactamase production common. Longer duration if undrainable abscesses. Intrinsic vancomycin resistance. High rates of resistance to quinupristin/ dalfopristin. Susceptibility testing important for choosing therapy as susceptibility of individual isolates varies. Probable diarrheal pathogen. Comments 28    Chapter 1  Infectious Agents and Drugs of Choice
  46. 46. All All All All Proteus mirabilis Proteus vulgaris and other indole-positive species Providencia spp. Host Category Propionibacterium acnes Pathogen 5–7 days 5–7 days ≥10 days ≥10 days 5–7 days 5–7 days ≥10 days ≥10 days PCS3 + AG or FQ + AG TMP/SMX or A/C PCS3 + AG or FQ Pyelonephritis, other invasive Cystitis, other nonserious Pyelonephritis, other invasive Carbapenem or BL/BLI Carbapenem or BL/BLI OCS3 PCS3 or AG or Carbapenem A/C ≥10 days ≥10 days PCS3 or FQ Ampicillin or FQ Pyelonephritis, other invasive TMP/SMX or OCS or FQ Clindamycin or Doxycycline or PCS3 or Linezolid Doxycycline PO or Minocycline PO Alternative Treatment 5–7 days Variable Variable Many weeks Many weeks Duration Cystitis, other nonserious Ampicillin PenG (high dose) or Vancomycin Invasive Cystitis, other nonserious Erythromycin topical or Clindamycin topical Recommended Treatment Acne vulgaris (inflammatory) Indication/ Type of Infection ≥10 days ≥10 days ≥10 days ≥10 days 5–7 days ≥10 days ≥10 days ≥10 days 5–7 days 5–7 days 5–7 days 5–7 days Variable Variable Variable Variable Many weeks Many weeks Duration Carbapenem if ESBL suspected. 1 Continued Isolates from urine/blood/CSF should be tested for ESBL. Usually associated with hardware. Consistently resistant to metronidazole. Increasing clindamycin resistance. Proteus UTI associated with urolithiasis. Plus nonantibiotic topical antiacne. Oral agents used for nonresponse to topicals or severe acne. Comments Chapter 1  Infectious Agents and Drugs of Choice    29
  47. 47. Host Category All All All Rickettsia rickettsii Rickettsia akari Rickettsia prowazekii Pseudomonas aeruginosa, All other species Pathogen APCS3/4 +/− AG or APPN + AG Doxycycline Meningitis Epidemic typhus Rickettsialpox Doxycycline Doxycycline APCS3/4 +/− AG or APPN + AG Pneumonia, bacteremia, sepsis Rocky Mountain Spotted Fever FQ (ciprofloxacin) or APCS or APPN Recommended Treatment Uncomplicated UTI, other nonserious Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 7–10 days 3–5 days ≥14 days 7–10 days ≥14 days ≥14 days ≥14 days ≥10 days ≥10 days ≥10 days Duration CHL or FQ CHL CHL Carbapenem +/− AG Carbapenem +/− AG FQ + AG AG Carbapenem Alternative Treatment 7–10 days 7–10 days 3–5 days 7–10 days ≥14 days ≥14 days ≥14 days ≥10 days ≥10 days Duration Treat until at least 3 days afebrile. Doxycycline drug of choice even <8 yr old. Use doxycycline for pregnant women if severe illness and/ or chloroquine not available. Treat until at least 3 days afebrile. Treat until at least 3 days afebrile. Doxycycline drug of choice even <8 yr old. Cultures negative at least 10 days. Comments 30    Chapter 1  Infectious Agents and Drugs of Choice
  48. 48. All All All Rickettsia—other species Salmonella typhi (type D) Host Category Rickettsia typhi Pathogen PCS3 or FQ IV Azithromycin PO or PCS3 or FQ PO Typhoid fever—mild Doxycycline Doxycycline Recommended Treatment Typhoid fever Endemic typhus Indication/ Type of Infection 7–14 days 7–14 days 7 days 10–14 days 10–14 days 7–10 days 5–10 days Duration Amoxicillin PO or TMP/SMX PO or CHL PO Azithromycin CHL CHL Alternative Treatment 10–14 days 10–14 days 10–14 days 10–14 days 7–10 days 5–10 days Duration 1 Continued Shorter courses for milder disease in nonimmunocompromised host may be effective. Treat until at least 3 days afebrile. Doxycycline drug of choice even <8 yr old. Treat until at least 3 days afebrile. High rates of FQ resistance in some geographic areas. Dexamethasone may be appropriate adjunctive therapy. May switch to oral therapy to complete course once improvement established. Clinical failure despite in vitro activity of 1st ceph and 2nd ceph, AG, furazolidone. Comments Chapter 1  Infectious Agents and Drugs of Choice    31
  49. 49. Salmonella, non-typhi Pathogen Gastroenteritis Infant <3 mo old; sickle cell; splenic dysfunction PCS3 Meningitis PCS3 or Amoxicillin or TMP/SMX No antibiotics PCS3 Localized, nonmeningeal disease (osteomyelitis, abscess) Gastroenteritis Same as for typhoid fever Recommended Treatment Enteric fever, bacteremia Indication/ Type of Infection Normal All Host Category TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 5 days 5 days 5 days 6 wk ≥4 wk Duration FQ or Azithromycin FQ Alternative Treatment 5 days ≥4 wk Duration FQ may be first choice in adults. Avoid amoxicillin and TMP/SMX in areas of prevalent resistance unless susceptibility proved. Supportive treatment only. May change to ampicillin IV if isolate proved susceptible. May change to ampicillin IV if isolate proved susceptible. Comments 32    Chapter 1  Infectious Agents and Drugs of Choice
  50. 50. Gastroenteritis, dysentery Gastroenteritis, dysentery Bacteremia, invasive Child Adult All ages Shigella sonnei, Shigella dysenteriae, Shigella boydii, Shigella flexneri Invasive (bacteremia, meningitis, pneumonia) Indication/ Type of Infection All Host Category Serratia marcescens Pathogen Ceftriaxone FQ or Azithromycin Azithromycin or Cefixime or FQ Imipenem + AG or Meropenem + AG Recommended Treatment TMP/SMX or Ceftriaxone FQ ≥10 days Ampicillin or Ceftriaxone PCS3/4 + AG or APPN + AG or FQ Alternative Treatment 5 days 5 days 5 days 3 days 5 days All: variable, ≥21 days for meningitis Duration ≥10 days 5 days 2 days 2–5 days 2–5 days All: variable, ≥21 days for meningitis Duration Invasive disease is uncommon. 1 Continued TMP/SMX if susceptibility confirmed. For neonatal meningitis, perform daily CSF cultures until sterile. Treat 10–14 days after first sterile CSF culture. Susceptibility testing should guide therapy. Consider CGD evaluation for non-neonates. Ampicillin and TMP/SMX resistance high in many areas; indicated if susceptibility confirmed. Mixed results for efficacy of cefixime. Treat for 7–10 days in immunocompromised hosts. Comments Chapter 1  Infectious Agents and Drugs of Choice    33
  51. 51. Staphylococcus aureus; methicillin-susceptible S. aureus (MSSA) Pathogen All Host Category 4–6 wk (gentamicin 3–5 days) 10 days from negative culture 10 days SS-pen IV + gentamicin SS-pen IV +/− rifampin SS-pen IV + clindamycin Endocarditis (native valve) CNS Toxic shock syndrome Vancomycin + clindamycin Vancomycin IV +/− rifampin Vancomycin + gentamicin Vancomycin IV ≥3 wk Bacteremia/sepsis/ pneumonia/ empyema Clindamycin IV or Vancomycin IV SS-pen IV SS-pen IV or 1st ceph IV Arthritis 4–6 wk 4–6 wk Clindamycin or TMP/SMZ or Doxycycline Alternative Treatment Clindamycin IV or Vancomycin IV SS-pen IV or 1st ceph IV Osteomyelitis 10 days 10 days 10 days 10 days Duration 3–4 wk 3–4 wk 1st ceph or SS-pen or BL/BLI or Macrolide Recommended Treatment Superficial Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 10 days 10 days from negative culture 4–6 wk (gentamicin 3–5 days) ≥3 wk 3–4 wk 3–4 wk 4–6 wk 4–6 wk 10 days 10 days Duration Eliminate either antibiotic once stable and can complete PO. Some experts recommend adding IVIg. Some experts add rifampin and/or gentamicin in selected cases. Switch from IV to PO when good clinical response. Comments 34    Chapter 1  Infectious Agents and Drugs of Choice
  52. 52. Staphylococcus aureus; methicillin-resistant S. aureus (MRSA) Pathogen All Host Category 10 days from negative culture 10 days Vancomycin IV Vancomycin IV +/− rifampin Vancomycin + clindamycin Endocarditis (native valve) CNS Toxic shock syndrome 4–6 wk Linezolid or Daptomycin Linezolid IV Daptomycin ≥3 wk Vancomycin IV Bacteremia/sepsis/ pneumonia/ empyema Linezolid or Daptomycin Vancomycin IV or Doxycycline (≥8 yr) or Linezolid Alternative Treatment All: 6 wk (osteomyelitis) 3–4 wk (arthritis) Clindamycin IV or Vancomycin IV Osteomyelitis, arthritis 10 days 10 days Duration Clindamycin or TMP/SMZ Recommended Treatment Superficial Indication/ Type of Infection 4–6 wk 4–6 wk ≥3 wk ≥3 wk All: 6 wk (osteomyelitis) 3–4 wk (arthritis) 10 days 10 days 10 days Duration 1 Confirm clindamycin susceptibility with D-test if erythromycin resistant. Continued Add rifampin for shunt infections. Gentamicin +/− rifampin for first 3–5 days for synergy. May add rifampin and/or gentamicin. No daptomycin for pneumonia. Ceftaroline approved for adults, but no data in children. Switch from IV to PO when good clinical response. Confirm clindamycin susceptibility with D-test. Comments Chapter 1  Infectious Agents and Drugs of Choice    35
  53. 53. All All All Streptobacillus moniliformis Streptococcus pneumoniae Host Category Stenotrophomonas maltophilia Pathogen Amoxicillin, high dose or Cefuroxime or Cefdinir or Cefpodoxime PCS3 Bacteremia, severe pneumonia (invasive, non-CNS) PenG procaine IM or PenG IV TMP/SMX Recommended Treatment Sinopulmonary infections, otitis media, pneumonia (non-CNS, noninvasive, nonsevere) Rat bite fever Pneumonia, bacteremia Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) ≥10 days (longer if focus of infection, e.g., bone) 10 days for all regimens 7–10 days for all regimens ≥10 days Duration Vancomycin IV or Clindamycin IV or Linezolid IV or Carbapenem IV Ampicillin IV or Cefuroxime IV or PCS3 or Erythromycin or Doxycycline or Clindamycin Azithromycin or Clindamycin or PCS3 Tic/clav or Ceftazidime Alternative Treatment All ≥10 days (longer if focus of infection, e.g., bone) 5 days 10 days 10 days (1 day for otitis media) 7–10 days for all regimens ≥10 days ≥10 days Duration Can switch to PO when stable in many cases. Susceptibility testing guides antibiotic options. Parenteral choices for more severe illnesses. Shorter courses (5–7 days) of oral β-lactams for acute, uncomplicated otitis media in healthy children age ≥6 yr without recent otitis. Minocycline or moxifloxacin often used if resistant to preferred and alternative agents. Duration depends on site and severity of infection. Course can be completed orally once patient stable and with good response. Comments 36    Chapter 1  Infectious Agents and Drugs of Choice
  54. 54. Pathogen Host Category 14 days 14 days PCS3 Vancomycin + PCS3 +/− rifampin Meningitis: penicillin nonsusceptible and PCS3 susceptible Meningitis: penicillin and PCS3 nonsusceptible 14 days 14 days PCS3 or AqPenG Meningitis, penicillin and PCS3 susceptible Duration Recommended Treatment Indication/ Type of Infection CHL or Vancomycin + rifampin or Linezolid Carbapenem IV or Vancomycin +/− rifampin Carbapenem IV or Vancomycin +/− rifampin Alternative Treatment All: 14 days All: 14 days 14 days 14 days Duration 1 Continued Susceptibility testing guides antibiotic options. Repeat LP 48–72 hr, especially if inadequate clinical improvement. Rifampin if clinical worsening, high-level cefotaxime/ceftriaxone resistance (MIC ≥ 4 mcg/ mL), and/or persistently positive CSF, but only if rifampin susceptible. If severe β-lactam allergy requires use of vancomycin, consider addition of rifampin. Vancomycin + PCS3 until susceptibilities known. Susceptibility testing guides antibiotic options. Susceptibility testing guides antibiotic options. Vancomycin + PCS3 until susceptibilities known. If severe β-lactam allergy requires use of vancomycin, consider addition of rifampin. Comments Chapter 1  Infectious Agents and Drugs of Choice    37
  55. 55. Pharyngitis; other noninvasive Invasive, nonendocarditis All All PenG IV PenVK PO >10 days 14–21 days (ampicillin or penicillin) 2–3 days (gentamicin) 10 days Ampicillin + gentamicin or Penicillin + gentamicin Meningitis, sepsis Group C, G Streptococcus PCS3 or Vancomycin All: ≥10 days, depending on site of infection Ampicillin or PenG PCS1, 2, 3 or Vancomycin OCS1, OCS2, or TMP/SMX PCS3 or Vancomycin Ceftriaxone + clindamycin or Vancomycin + clindamycin ≥10 days PenG IV + clindamycin Toxic shock syndrome, necrotizing fasciitis, other invasive Invasive (nonmeningitis, not sepsis) OCS1 or Erythromycin or Azithromycin or Clarithromycin Alternative Treatment 10 days 10 days One dose Duration PenVK PO or Amoxicillin PO or PenG benzathine IM Recommended Treatment Pharyngitis Indication/ Type of Infection All Host Category Group B Streptococcus Group A Streptococcus Pathogen TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) >10 days >10 days 10 days 10 days 14–21 days 14–21 days All: ≥10 days, depending on site of infection ≥10 days ≥10 days 5–10 days 10 days 5 days 10 days Duration May add gentamicin if tolerance suspected. High-dose ampicillin or penicillin used for meningitis. Gentamicin used until clinical response and CSF/blood sterile. Simplify to single antibiotic when patient stable. Adjunctive surgery often needed. Duration depends on site of infection. PenVK BID and amoxicillin BID or once daily acceptable. Some data for 5 days OCS1. Comments 38    Chapter 1  Infectious Agents and Drugs of Choice
  56. 56. Viridans streptococci Pathogen Penicillin PO or Amoxicillin or Ampicillin Penicillin IV or Ampicillin IV or Ceftriaxone PenG IV or Ceftriaxone IV or PenG IV+ gentamicin or Ceftriaxone + gentamicin Bacteremia, other invasive Native valve endocarditis, highly susceptible (Pen MIC ≤0.1) Usually neonate, altered immunity or intravascular catheter 4 wk 4 wk 2 wk 2 wk 10–14 days 10–14 days 10–14 days All: variable 4–6 wk (β-lactam) + 2 wk (gentamicin) PenG IV + gentamicin or Ceftriaxone + gentamicin Dental, soft tissue, noninvasive Endocarditis All Duration Recommended Treatment All Indication/ Type of Infection Host Category Vancomycin IV Vancomycin IV OCS or PSC or Vancomycin Vancomycin Alternative Treatment 4 wk 10–14 days All: variable 4–6 wk Duration 1 Continued Vancomycin only if intolerant of other regimen. Increasing penicillin-resistant strains, especially in oncology patients. Once-daily gentamicin not studied in pediatric endocarditis. If prosthetic valve/material or less susceptible organism, use 6 wk instead of 4. For highly resistant isolate, use 6 wk of [penicillin or ceftriaxone] plus 6 wk of gentamicin. Vancomycin only if penicillin and ceftriaxone contraindicated. Ceftriaxone preferred PCS. Must consider possible polymicrobial infections; vancomycin preferred by some experts for oncology patients because of growing PCN resistance. Comments Chapter 1  Infectious Agents and Drugs of Choice    39
  57. 57. Viridans streptococci (Coutinued) Pathogen Host Category 6 wk 6 wk 6 wk 6 wk Ampicillin IV + gentamicin or Penicillin IV+ gentamicin or Vancomycin IV + gentamicin Pen G IV or Ceftriaxone Pen G IV + gentamicin or Ceftriaxone + gentamicin Native valve endocarditis, resistant Prosthetic valve endocarditis, susceptible (Pen MIC ≤0.12) Prosthetic valve endocarditis, relatively or fully resistant (Pen MIC >0.12) 6 wk 4–6 wk 4–6 wk 4 wk/2 wk 4 wk/2 wk PenG IV/ gentamicin or Ceftriaxone/ gentamicin Native valve endocarditis, relatively resistant (Pen MIC >0.12 g/mL to ≤0.5 g/mL) Duration Recommended Treatment Indication/ Type of Infection TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) Vancomycin IV Vancomycin IV — Vancomycin IV Alternative Treatment 6 wk 6 wk — 4 wk Duration Gentamicin used for all 6 wk of PenG or ceftriaxone therapy. Vancomycin only if intolerant of other regimen. Gentamicin often added to Pen G or ceftriaxone for first 2 wk of treatment. Vancomycin only if intolerant of other regimen. Same as for enterococcal endocarditis. Vancomycin only if intolerant of other regimen. Vancomycin only if intolerant of other regimen. Comments 40    Chapter 1  Infectious Agents and Drugs of Choice
  58. 58. Treponema pallidum (syphilis) Pathogen PenG benzathine IM Latent ≥1 yr; latent unknown duration; tertiary without neurosyphilis Beyond infancy PenG benzathine IM or no antibiotic Mother adequately treated and infant evaluation normal PenG benzathine IM PenG IV or PenG procaine IM or PenG benzathine IM Mother’s treatment or response inadequate, but infant evaluation normal Primary; secondary; latent <1 yr PenG IV 50,000 units/kg/dose Q12 hr (<8 days old) or Q8 hr (>7 days old) Recommended Treatment Proven or probable congenital syphilis Indication/ Type of Infection Beyond infancy Infants Host Category Once weekly for 3 wk Once Once Once 10 days 10 days 10 days Duration Doxycycline or Tetracycline Doxycycline or Tetracycline PenG procaine IM 50,000 units/kg once daily Alternative Treatment 28 days 28 days 14 days 14 days 10 days Duration 1 Continued Doxycycline and tetracycline only used for penicillinallergic, nonpregnant patients. Penicillin-allergic pregnant women must be desensitized and treated with penicillin. Close clinical and serologic follow-ups essential, especially if no treatment given. Close clinical and serologic follow-ups essential, especially if single-dose regimen used. Close clinical and serologic follow-ups essential. Comments Chapter 1  Infectious Agents and Drugs of Choice    41
  59. 59. Doxycycline IV TMP/SMX PO or Doxycycline PO or Ciprofloxacin PO or Azithromycin PO All Symptomatic CNS Moderate to severe illness Vibrio cholerae Erythromycin IV/ PO Symptomatic respiratory Preterm neonates Doxycycline PO Urethritis All AqPenG IV Recommended Treatment Ureaplasma urealyticum Neurosyphilis; syphilitic eye disease Indication/ Type of Infection Beyond infancy Host Category Treponema pallidum (syphilis) (Coutinued) Pathogen TABLE 1-1  RECOMMENDED TREATMENT FOR BACTERIAL INFECTIONS (Continued) 10–14 days 3 days 1 dose 1 dose 1 dose 10 days 7 days 10–14 days Duration CHL IV Tetracycline PO or Furazolidone PO or Erythromycin PO or Ofloxacin PO Azithromycin (?) PO/IV Erythromycin PO or Azithromycin PO [PenG procaine IM + probenecid] or Ceftriaxone Alternative Treatment Unknown Unknown 10–14 days 3 days 3 days 10 days 1 dose 7 days 10–14 days 10–14 days Duration Very limited data. Fluid/electrolyte most important part of prescription. Tetracycline and doxycycline preferred for patients ≥8 yr old. Ciprofloxacin if ≥18 yr old. Variable resistance. Azithromycin preferred during pregnancy. Route depends on degree of illness. Pyloric stenosis risk with erythromycin. Scant data for azithromycin treatment. Penicillin-allergic pregnant women must be desensitized and treated with penicillin. Ceftriaxone only in nonpregnant women if penicillin cannot be used. Erythromycin ×14 days preferred for children <8 yr old. Comments 42    Chapter 1  Infectious Agents and Drugs of Choice
  60. 60. Yersinia pestis (plague) Vibrio vulnificus, Vibrio parahaemolyticus, other species Yersinia enterocolitica, Yersinia pseudotuberculosis Pathogen TMP/SMX or PCS3 or FQ CHL IV Sepsis or other invasive illness All TMP/SMX or PCS3 or FQ Meningitis, endophthalmitis, or shock Enterocolitis Immunocompromised None ≥7–10 days ≥7–10 days ≥7–10 days Variable Variable Variable Doxycycline + ceftazidime Streptomycin IM Gentamicin IM/IV Enterocolitis Pseudoappendicitis Mesenteric adenitis Normal Duration Recommended Treatment Bubonic/ pneumonic plague Bacteremia/sepsis Wound Indication/ Type of Infection All Host Category — Tetracycline or Doxycycline or Piperacillin or AG Tetracycline IV or Doxycycline IV Tetracycline or Doxycycline or Piperacillin or AG FQ or PCS3 Alternative Treatment — ≥7–10 days ≥7–10 days Variable Variable Variable Variable Duration 1 Treat until afebrile several days. Tetracycline and doxycycline for ≥8 yr old. FQ for ≥18 yr old. Y. enterocolitica: consider iron overload syndromes. Prompt debridement for wound infections and necrotizing fasciitis. Antibiotics may limit duration of shedding, but no clinical benefit. Comments Chapter 1  Infectious Agents and Drugs of Choice    43
  61. 61. Mycobacterium tuberculosis* Pathogen Pregnancy and breast-feeding Immunocompetent Host Category Treat only after consultation with a TB specialist Latent infection; isoniazid and rifampin-resistant Isoniazid + pyridoxine Rifampin Latent infection; isoniazid-resistant Latent infection All ages:   Isoniazid or (if ≥12 yr)   Isoniazid + rifapentine Recommended Treatment Latent infection (positive TST, no disease); isoniazidsusceptible Indication/Type of Infection 9 mo 9 mo 6 mo 12 wk 12 wk 9 mo Duration 2–11 yr old:   Isoniazid +   rifapentine or   Rifampin <2 yr old:   Rifampin Alternative Treatment 6 mo 12 wk 12 wk 6 mo Duration Treatment with isoniazid should be avoided during the first trimester. However, for those at increased risk for progression to active disease, isoniazid treatment should not be delayed based on pregnancy alone, including during the first trimester. Isoniazid is secreted in human milk, but no adverse effects to infants have been detected. 12-wk combination therapy equally preferred if ≥12 yr; alternative if 2–11 yr old (limited data); not recommended if <2 yr old. Isoniazid alone is given by DOTS daily or twice weekly; isoniazid plus rifapentine combination is given weekly by DOTS. Comments TABLE 1-2  RECOMMENDED TREATMENT FOR MYCOBACTERIAL INFECTIONS (for notes and abbreviations used in this table, see p. xiii.) II.  RECOMMENDED TREATMENT FOR MYCOBACTERIAL INFECTIONS 44    Chapter 1  Infectious Agents and Drugs of Choice
  62. 62. Pathogen Latent infection Pulmonary and extrapulmonary, drug-susceptible disease (excluding meningitis or disseminated/ miliary TB) All Indication/Type of Infection Immunocompromised, HIV-infected Host Category 6 mo 6 mo 2 mo 2 mo 9 mo 9 mo Isoniazid + pyridoxine Isoniazid + rifampin + pyrazinamide + ethambutol Duration Recommended Treatment Aminoglycoside (streptomycin; alternative: kanamycin, amikacin, capreomycin) may be used in place of ethambutol Alternative Treatment Duration 1 Continued May discontinue 4th drug if isolate is fully drug-susceptible and disease is not considered high burden (pulmonary TB with extensive parenchymal involvement, cavitary disease). Corticosteroids may be considered as adjunctive therapy for 4–6 wk for patients with pleuritis or pericarditis. 12-wk isoniazid-rifapentine can be considered for HIV-infected children not taking ART and other immunocompromised children. Beware of ART and other drug interactions with rifampin and rifapentine. Consultation with a specialist is recommended. DOT is advised. Comments Chapter 1  Infectious Agents and Drugs of Choice    45
  63. 63. Mycobacterium tuberculosis* (Coutinued) Pathogen Pregnancy Host Category 9–12 mo 9–12 mo 2 mo 2 mo 2 mo 2 mo Duration Isoniazid + rifampin + pyrazinamide + [ethionamide or ethambutol or aminoglycoside] Isoniazid + rifampin + ethambutol + pyridoxine Meningitis or disseminated/ miliary TB Pulmonary and extrapulmonary disease 9 mo 9 mo 2 mo 9 mo Treat only after consultation with a TB specialist Recommended Treatment Pulmonary and extrapulmonary disease—possibly multidrugresistant or extensively drug resistant isolate Indication/Type of Infection TABLE 1-2  RECOMMENDED TREATMENT FOR MYCOBACTERIAL INFECTIONS (Continued) Isoniazid + rifampin + pyrazinamide + pyridoxine Alternative Treatment 6 mo 6 mo 2 mo 6 mo Duration Although teratogenicity data are not available, pyrazinamide can probably be used safely during pregnancy and is recommended by the World Health Organization and the International Union against Tuberculosis and Lung Disease. If pyrazinamide is not included in initial treatment regimen, treatment should be for at least 9 mo. If susceptibility to isoniazid, rifampin, and pyrazinamide is confirmed, the fourth drug can be discontinued. Usual aminoglycoside: streptomycin; alternatives: kanamycin, amikacin, capreomycin. Corticosteroid (2 mg/kg/day prednisone, maximum 60 mg/day for 4–6 wk followed by taper) is also indicated for meningitis once anti-TB therapy is begun. Comments 46    Chapter 1  Infectious Agents and Drugs of Choice
  64. 64. Congenital infection Host Category Mycobacterium avium complex Immunocompetent NONTUBERCULOUS MYCOBACTERIA† Mycobacterium All bovis Pathogen 9–12 mo 9–12 mo Treat as above for TB disease, depending on antibiotic susceptibility. Duration Isoniazid + rifampin + ethionamide or ethambutol or aminoglycoside† Excision of affected node(s) Meningitis Lymphadenitis At least 12 mo At least 12 mo 2 mo 2 mo 2 mo Isoniazid + rifampin Isoniazid + rifampin + pyrazinamide + amikacin Recommended Treatment Pulmonary and extrapulmonary disease, excluding meningitis Pulmonary and extrapulmonary disease Indication/Type of Infection [Clarithromycin or Azithromycin] + [ethambutol and/or (rifampin or rifabutin)] Alternative Treatment ≥3 mo ≥3 mo ≥3 mo ≥3 mo ≥3 mo Duration 1 Continued Pharmacologic therapy is recommended if excision is incomplete or if disease recurs. Recommended treatment for M. bovis is based on treatment trials for M. tuberculosis. All strains of M. bovis are resistant to pyrazinamide. Usual aminoglycoside: streptomycin; alternatives: kanamycin, amikacin, capreomycin. Add corticosteroid if meningitis is confirmed. Send placenta for TB culture and pathologic examination. Comments Chapter 1  Infectious Agents and Drugs of Choice    47
  65. 65. Immunocompetent or immunocompromised All All Mycobacterium kansasii Mycobacterium marinum Host Category Mycobacterium avium complex (Coutinued) Pathogen Duration Cutaneous infection Osteomyelitis Pulmonary infection Surgical debridement + Rifampin + ethambutol + isoniazid Rifampin or TMP/SMX or Clarithromycin or Doxycycline ≥3 mo ≥3 mo ≥3 mo ≥3 mo All: prolonged, variable Treat only in consultation with an expert. Initial recommended therapy with 3–4 drugs, including [clarithromycin or azithromycin] + ethambutol + [rifampin or rifabutin] +/− [amikacin or streptomycin] +/− ciprofloxacin [Rifampin + ≥3 mo ethambutol + ≥3 mo isoniazid] ≥3 mo Alternative Treatment Disseminated disease 12 mo 12 mo 12 mo 12 mo Duration [Clarithromycin or Azithromycin] + ethambutol + [rifampin or rifabutin] Recommended Treatment Pulmonary infection Indication/Type of Infection TABLE 1-2  RECOMMENDED TREATMENT FOR MYCOBACTERIAL INFECTIONS (Continued) Minor infection may heal without therapy. Extensive lesions may require surgical debridement. Isoniazid and pyrazinamide resistant. Resistant to pyrazinamide. Treatment for 12 mo followed by suppressive therapy. Amikacin or streptomycin can be added initially for severe disease. Comments 48    Chapter 1  Infectious Agents and Drugs of Choice
  66. 66. All All Mycobacterium fortuitum Host Category Mycobacterium ulcerans Pathogen Duration Comments Catheter removal + See Comment Amikacin + meropenem, followed by [clarithromycin or doxycycline‡ or TMP/SMX or ciprofloxacin] Catheter infection 1 Continued Definitive therapy should be based on susceptibility testing. Duration of therapy should be determined in consultation with an infectious disease specialist. See Comment Amikacin + meropenem, followed by [clarithromycin or doxycycline§ or TMP/SMX or ciprofloxacin] 8 wk 8 wk Duration Serious infection Excision of tissue + rifampin + ciprofloxacin Alternative Treatment Duration of therapy should be determined in consultation with an infectious disease specialist. Recommended Treatment Cutaneous and bone Excision of tissue + infection Rifampin + 8 wk streptomycin 8 wk Cutaneous infection Excision of tissue Indication/Type of Infection Chapter 1  Infectious Agents and Drugs of Choice    49
  67. 67. Mycobacterium chelonae Mycobacterium abscessus Pathogen Variable Variable [Tobramycin + (meropenem or linezolid) + clarithromycin] Disseminated cutaneous infection Variable Clarithromycin + amikacin + cefoxitin Catheter removal + tobramycin + clarithromycin Variable Duration Clarithromycin + amikacin + cefoxitin Recommended Treatment Catheter infection Pulmonary infection Patients with cystic fibrosis All Otitis media Indication/Type of Infection All Host Category TABLE 1-2  RECOMMENDED TREATMENT FOR MYCOBACTERIAL INFECTIONS (Continued) Meropenem may be used in place of cefoxitin. Meropenem may be used in place of cefoxitin. Alternative Treatment Duration Surgical resection may be required. Susceptibility testing should be performed. May not always require treatment as it is difficult to establish if mycobacteria are only colonizers or true pathogens. May require debridement. Susceptibility testing should be performed— amikacin resistance occurs in 50% of isolates. Comments 50    Chapter 1  Infectious Agents and Drugs of Choice
  68. 68. Cytomegalovirus Pathogen Neonate Immunocompromised Host Category Ganciclovir, IV indefinitely Long-term suppression of ocular infection Ganciclovir, IV for 6 wk Ganciclovir IV Ocular infection Symptomatic congenital infection involving the central nervous system ≤28 days of life Ganciclovir, IV for 14–21 days Recommended Treatment GI tract, lungs, viremia Indication Valganciclovir Foscarnet IV or Cidofovir IV or Valganciclovir PO Valganciclovir PO or Foscarnet IV or Cidofovir IV Foscarnet IV or Cidofovir IV or Valganciclovir PO Alternative Treatment TABLE 1-3  RECOMMENDED TREATMENT FOR VIRAL INFECTIONS (for notes and abbreviations used in this table, see p. xiv.) III.  RECOMMENDED TREATMENT FOR VIRAL INFECTIONS 1 Continued Data to support optimal use and duration of ganciclovir for this indication are controversial. Suppressive therapy for HIV-infected patients should continue until immune reconstitution has been achieved. For treatment of pulmonary or GI infection, immunoglobulin or CMV immunoglobulin may be used together with ganciclovir. Long-term suppressive therapy is used to prevent relapse in patients with HIV infection. Cidofovir should be administered with probenecid and hydration. Comment Chapter 1  Infectious Agents and Drugs of Choice    51
  69. 69. [Acyclovir PO or Famciclovir PO or Valacyclovir PO] for 7–10 days or Acyclovir IV for 5–7 days Genital (first episode) Herpes simplex (HSV) Immunocompetent [Interferon alpha-2b or pegylated Interferon alpha, subcutaneously or IM] + ribavirin, PO, for 12–48 wk depending on virologic response and virus genotype Chronic infection, ≥3 yr old Hepatitis C Recommended Treatment Interferon alpha-2b or pegylated Interferon alpha-2a, subcutaneously Indication Chronic disease with evidence of ongoing viral replication Host Category Hepatitis B Pathogen TABLE 1-3  RECOMMENDED TREATMENT FOR VIRAL INFECTIONS (Continued) Lamivudine (for children >2 yr old); adefovir (for children >11 yr old); Telbivudine (for those >16 yr old) Alternative Treatment May switch to PO to complete. Treatment of chronic hepatitis B infection in children is under continued investigation, and some drugs used to treat adults are not approved for children. Specialists in hepatology should be consulted. If lamivudine is used to treat children coinfected with HIV and hepatitis B, the lamivudine dose used should be the approved dose for treating HIV infection. Children with symptomatic hepatitis C disease or histologically advanced pathologic features should be considered for treatment in consultation with a gastroenterologist or infectious disease consultant. All patients with hepatitis C should be immunized against hepatitis A and B. Famciclovir and valacyclovir are licensed only for adolescents and adults. Comment 52    Chapter 1  Infectious Agents and Drugs of Choice
  70. 70. Pathogen Acyclovir IV (30 mg/kg/day divided into 3 doses) for 7–14 days Acyclovir PO for 7–14 days or Famciclovir PO or Valacyclovir PO Any non-CNS site Mucocutaneous Acyclovir IV (30–45 mg/kg/day divided into 3 doses) for at least 21 days CNS (encephalitis) (postneonatal) Immunocompromised Acyclovir PO (400 mg BID) or Famciclovir PO (250 mg BID) or Valacyclovir PO (1000 mg/day)] for as long as 12 mo continuously Suppression of recurrent mucocutaneous outbreaks Acyclovir IV (60 mg/kg/day divided into 3 doses) for 14 (skin, eye, mucous membrane involvement) to 21 days (disseminated or CNS involvement) [Acyclovir PO or Famciclovir PO or Valacyclovir PO] for 5 days or Acyclovir IV for 5–7 days Genital (recurrent) Any Recommended Treatment Indication Neonate Host Category Foscarnet IV Foscarnet IV Alternative Treatment 1 Continued Use foscarnet for HSV infection resistant to acyclovir. Use foscarnet for HSV infection resistant to acyclovir. Treat until infection resolves. Famciclovir and valacyclovir are licensed only for adolescents and adults. May switch to PO to complete. Famciclovir and valacyclovir are licensed only for adolescents and adults. Comment Chapter 1  Infectious Agents and Drugs of Choice    53
  71. 71. Herpes simplex (HSV) (Coutinued) Influenza A and B Pathogen Indication Keratoconjunctivitis Treatment Treatment Host Category All ≥2 weeks of age ≥7 yr of age Oseltamivir PO for 5 days or Zanamivir, inhalation, for 5 days [Trifluridine or Iododeoxyuridine or Vidarabine] topical Oseltamivir PO for 5 days Recommended Treatment TABLE 1-3  RECOMMENDED TREATMENT FOR VIRAL INFECTIONS (Continued) Alternative Treatment Most effective if treatment is initiated within 48 hr of onset of symptoms. Treatment may be beneficial if initiated after 48 hr in patients with severe, complicated, or progressive illness or those requiring hospitalization. Amantadine and rimantadine have been used to treat influenza A, but most isolates since 2006 have been resistant. Most effective if treatment is initiated within 48 hr of onset of symptoms. Treatment may be beneticial if initiated after 48 hr in patients with severe, complicated, or progressive illness or those requiring hospitalization. Amantadine and rimantadine have been used to treat influenza A, but most isolates since 2006 have been resistant. For current recommendations see www.cdc.gov/flu/ professionals/antivirals/index.htm or www.aapredbook.org/flu. Consult an ophthalmologist. Comment 54    Chapter 1  Infectious Agents and Drugs of Choice
  72. 72. Indication Acyclovir IV for 7–10 days Acyclovir PO or IV for 7–10 days Varicella Zoster Acyclovir PO or IV for 5–7 days Zoster Immunocompromised Acyclovir PO or IV for 5 days Varicella Immunocompetent Varicella Ribavirin, aerosol via small-particle generator, 18 hr/day for 3–7 days IVIG Recommended Treatment Bronchiolitis/pneumonia, severe Immunocompromised with persistent anemia Host Category Respiratory syncytial virus Parvovirus Pathogen Famciclovir PO for 7 days or Valacyclovir PO for 7 days or Foscarnet IV for up to 3 wk Foscarnet IV Famciclovir PO for 7 days or Valacyclovir PO for 7 days Alternative Treatment 1 Famciclovir and valacyclovir are licensed only for adolescents and adults. Use foscarnet for varicella infection resistant to acyclovir. Use of oral acyclovir instead of or to complete an IV therapy course is used by some experts for patients thought to be at low risk for severe disease. Use foscarnet for varicella infection resistant to acyclovir. Famciclovir and valacyclovir are licensed only for adolescents and adults. Longer treatment may be required for some patients. Effectiveness has been questioned. Not routinely recommended. Begin within 24 hr of symptoms. Treatment is indicated only for individuals at increased risk for moderate to severe varicella. Comment Chapter 1  Infectious Agents and Drugs of Choice    55

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