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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.
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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.

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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.

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