A systematic review and meta-analysis of anti-pseudomonal penicillins and carbapenems in pediatric febrile neutropenia

Carbapenems represent a broad-spectrum alternative to anti-pseudomonal penicillin (APP) combination or single-agent therapy for the management of pediatric febrile neutropenia (FN). Our primary objective was to describe the risk of treatment failure in children treated with an APP or carbapenem as initial empiric treatment for FN. Our secondary objective was to compare outcomes of APP versus carbapenem therapy in this population. An electronic search of Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials was performed. We limited studies to prospective pediatric trials of FN in which at least one treatment arm consisted of an APP (with or without an aminoglycoside) or a carbapenem. Of 7,281 articles reviewed, 27 studies comprising 30 treatment regimens were included for meta-analysis. Treatment failure, including antibiotic modification, occurred in 41% (95% confidence interval (CI) 32-50%), 34% (95% CI 27-41%), and 35% (95% CI 24-45%) of patients treated with APP-aminoglycoside, APP monotherapy, and carbapenem monotherapy regimens, respectively. There was no significant difference in treatment failure including antibiotic modification, infection-related mortality, or adverse events when comparing either APP regimen with carbapenem monotherapy. Although a limited number of studies were available, when stratified by FN risk group, no differences were seen in any outcome. Our meta-analysis suggests that APP-aminoglycoside, APP monotherapy, and carbapenem monotherapy are all efficacious therapeutic options for the empiric management of pediatric FN.