Meta-analysis of efficacy and safety of cefepime

Article Outline

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In this issue of The Journal, Adderson et al report a systematic review and meta-analysis of randomized controlled trials of the fourth generation cephalosporin agent, cefepime, in children following the Food and Drug Administration's review of the report of increased all-cause mortality with cefepime monotherapy versus comparator in a meta-analysis predominantly involving adults. The meta-analysis of pediatric patients by Adderson et al does not support excess all-cause mortality or clinical failure associated with cefepime therapy in trials. With additional information and review of adult data, the Food and Drug Administration had concluded similarly.

Adderson et al point to the multiple methodologic flaws in studies they used to attempt to test the hypothesis regarding relative safety and efficacy of cefepime. Such flaws are common to many trials of pharmaceutical agents in children. Even in randomized comparator-controlled trials, aspects that limit precision of findings are common, such as heterogeneity of patient populations, nonconcealment of treatment group, allowance of additional therapies, lack of consistency of 30-day all-cause mortality data, small number of subjects, and low rate of outcomes of critical importance, whose temper practitioners' ability to draw rock-solid conclusions to know what is best, or not best, for patients. Praise for the attempted meta-analysis, less for the depth of the trials' data.

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