Less is more: Combination antibiotic therapy for the treatment of gram-negative bacteremia in pediatric patients

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.