Single Drug May Suffice for Gram-Negative Bacteremia in Kids

Laurie Barclay, MD

April 07, 2014

Routine addition of an aminoglycoside to a β-lactam as empirical therapy for children with Gram-negative bacteremia may not be helpful except in those with risk factors for multidrug-resistant (MDRGN) organisms, according to a retrospective cohort study published online April 7 in Pediatrics.

"Existing data do not demonstrate a need for combination therapy after antimicrobial susceptibility data indicate adequate in vitro activity with β-lactam monotherapy," write Anna C. Sick, MD, MPH, from the Department of Pediatrics, University of Pittsburgh Medical Center in Pennsylvania, and colleagues. "However, the role of empirical combination therapy for the treatment of Gram-negative bacteremia in children remains unsettled."

The study cohort consisted of 226 matched pairs of children treated with empirical combination therapy vs empirical monotherapy for Gram-negative bacteremia at Johns Hopkins Hospital in Baltimore, Maryland, from 2004 to 2012. The investigators created these pairs, which were well-balanced for baseline characteristics, using 1:1 nearest-neighbor propensity-score matching.

Combination Therapy Beneficial Only in MDRGN Infections

Both groups had similar 10-day mortality (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.28 - 1.71) and duration of bacteremia (reduction with combination therapy, −0.51 days; 95% confidence interval, −2.22 to 1.48 days).

In terms of patient subgroups, there was no survival benefit with combination therapy among severely ill patients, defined as a pediatric risk of mortality III score 15 or higher, or among severely neutropenic patients, defined as an absolute neutrophil count of 100 or fewer cells/mL.

In contrast, there was a survival benefit for empirical combination therapy among children with blood cultures positive for MDRGN organisms (OR, 0.70; 95% CI, 0.51 - 0.84; P < .01).

"Although there appears to be no advantage to the routine addition of an aminoglycoside to a β-lactam as empirical therapy for children who have Gram-negative bacteremia, children who have risk factors for MDRGN organisms appear to benefit from this practice," the authors write.

Limitations of this study include that it is a single-center study conducted at a tertiary care referral center, limiting generalizability; possible unmeasured residual confounding; and small numbers of children in various subgroups.

"Our findings indicate that combination empirical therapy does not appear to add a clinical benefit for the routine management of children who have Gram-negative bacteremia when an appropriately broad β-lactam agent guided by local epidemiology is selected," the study authors conclude. "Combination empirical therapy improves the outcomes of patients growing MDRGN organisms in the bloodstream and careful review of patient risk factors is needed to identify these patients to ensure early, appropriate therapy is prescribed."

A Thrasher Research Foundation award to one of the study authors supported this study. Two other authors are the recipients of Pfizer Independent Grants for Learning and Change unrelated to the present study. An additional study author has a patent application pending for a point-of-care diagnostic test to optimize the initial selection of antibiotics for urinary tract infections.

Pediatrics. Published online April 7, 2014.


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