August 8, 2013
Robert S. Baltimore, MD reviewing Tamma PD et al. JAMA Pediatr 2013 Aug 5.
In a large, single-center study, using a β-lactam antibiotic plus an aminoglycoside rather than β-lactam monotherapy had no survival advantage and was associated with higher nephrotoxicity risk.
The role of combination antibiotic therapy — using a β-lactam antibiotic plus an aminoglycoside rather than a β-lactam alone — as culture-directed therapy for gram-negative bacteremia is unsettled in pediatric practice, although most studies in adults show no advantage with the combination. In a retrospective study involving pediatric patients at a single major medical center in the U.S., researchers examined 10 years of data to determine whether combination therapy affects survival and whether it increases the risk for renal injury.
They identified 879 children aged ≤18 who were admitted between 2002 and 2011 with blood cultures growing species of Enterobacteriaceae, Pseudomonas, or Acinetobacter. The most commonly isolated organisms were Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. In all, 537 children (61%) received a β-lactam plus an aminoglycoside as definitive therapy for ≥48 hours after antibiotic susceptibilities were finalized, and 342 (39%) received a β-lactam alone as definitive therapy. The investigators used propensity score weighting combined with multivariable logistic regression to account for more-serious illness and a higher level of medical support in patients receiving combination therapy.
Sixty-four (7%) of the children died within 30 days, with no significant between-group difference. Nephrotoxicity developed in 170 children (19%) — 25% of children in the combination therapy group and 10% of those in the monotherapy group (P<0.001). There was no long-term follow-up of renal function, however.
The authors claim that this study is the first to address the comparative advantages of combination versus monotherapy for gram-negative bacteremia in children. I have accepted as probably applicable to children the extensive data from adult studies suggesting no survival advantage — but increased risk for renal toxicity — with combination therapy. The findings from the present study are comforting and should be helpful in persuading colleagues not to add a second antibiotic just because “two are better than one.” Whether the findings extend to neonates aged <1 month, however, is not clear from the data presented.