We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation | Comparative Effectiveness Research

Less Is More:  Combination Antibiotic Therapy for the Treatment of Gram-Negative Bacteremia in Pediatric Patients

Pranita D. Tamma, MD, MHS1; Alison E. Turnbull, DVM, MPH2; Anthony D. Harris, MD, MPH3; Aaron M. Milstone, MD, MHS1; Alice J. Hsu, PharmD, BCPS4; Sara E. Cosgrove, MD, MS5
[+] Author Affiliations
1Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
3Department of Medicine, University of Maryland School of Medicine, Baltimore
4Department of Pharmacy, Johns Hopkins Hospital, Baltimore, Maryland
5Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
JAMA Pediatr. 2013;167(10):903-910. doi:10.1001/jamapediatrics.2013.196.
Text Size: A A A
Published online

Importance  Definitive combination antibiotic therapy with a β-lactam and an aminoglycoside for the treatment of gram-negative bacteremia is commonly prescribed in pediatric patients; however, its efficacy and toxicity relative to β-lactam monotherapy are unknown.

Objective  To determine whether definitive combination antibiotic therapy affects mortality and nephrotoxicity in pediatric patients with gram-negative bacteremia.

Design, Setting, and Participants  Retrospective cohort study including pediatric patients (aged ≤18 years) with gram-negative bacteremia hospitalized at the Johns Hopkins Children’s Center between 2002 and 2011.

Main Outcomes and Measures  Outcomes included 30-day mortality and nephrotoxicity classified according to the pediatric RIFLE (risk for renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, and end-stage renal disease) criteria. To account for nonrandom assignment of combination therapy, propensity score weighting was combined with multivariable logistic regression to estimate the effect of combination therapy on mortality and nephrotoxicity.

Results  Of the 879 eligible pediatric patients with bacteremia, 537 (61.1%) received combination therapy. After propensity score adjustment, baseline demographic and clinical characteristics between the groups were well balanced. There was no association between combination therapy and 30-day mortality (odds ratio, 0.98; 95% CI, 0.93-1.02; P = .27). There were 170 patients (19.3%) with evidence of acute kidney injury, including 135 (25.1%) and 35 (10.2%) in the combination therapy and monotherapy arms, respectively. Patients receiving combination therapy had approximately twice the odds of nephrotoxicity compared with those receiving monotherapy (odds ratio, 2.15; 95% CI, 2.09-2.21).

Conclusions and Relevance  The use of β-lactam monotherapy for gram-negative bacteremia in pediatric patients reduces subsequent nephrotoxicity without compromising survival.

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal


Place holder to copy figure label and caption
Study Design

Design of study in pediatric patients receiving combination antibiotic therapy vs monotherapy for definitive treatment of gram-negative bacteremia (due to Enterobacteriaceae, Pseudomonas species, or Acinetobacter species) between 2002 and 2011. Some patients met more than 1 exclusion criterion.

Graphic Jump Location




Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 2

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles