A meta-analysis of clinical studies of imipenem-cilastatin for empirically treating febrile neutropenic patients

Abstract

There are many clinical studies comparing antibiotic treatments, but the majority are too small to have sufficient power to be reasonably certain of detecting statistically a moderate treatment effect. For example, few of the 19 studies published on imipenem-cilastatin for empirically treating febrile neutropenic patients were able to show any significant treatment effect in either direction when compared with alternative regimens. We therefore undertook a meta-analysis of these studies and made 21 pairwise comparisons of a control regimen with imipenem-cilastatin. Eleven comparisons were made between imipenem-cilastatin and a beta-lactam-aminoglycoside combination, and a further 10 between the carbapenem and a beta-lactam regimen either alone or combined with a glycopeptide or other beta-lactam antibiotic. These two data sets were analysed separately. Imipenem-cilastatin demonstrated a beneficial treatment effect over that achieved by aminoglycoside containing control regimens, yielding a typical odds ratio (OR) of 0.77 (95% CI 0.61 to 0.98). A beneficial treatment effect for the carbapenem regimen was also shown against regimens that did not include an aminoglycoside, with the typical OR being 0.67 (95% CI 0.54 to 0.84). Although there was clinical heterogeneity between studies, the treatment effect itself was relatively homogenous. These results show meta-analysis to be a useful aid for interpreting the data from clinical studies that are intrinsically too small to provide conclusive results.