Comprehensive evaluation of ciprofloxacin-aminoglycoside combinations against Enterobacteriaceae and Pseudomonas aeruginosa strains.

Abstract

The in vitro activities of antibiotic combinations containing ciprofloxacin and either gentamicin, sisomicin, netilmicin, amikacin, or tobramycin were evaluated by checkerboard assay (agar dilution method). A total of 220 strains of Enterobacteriaceae and Pseudomonas aeruginosa (11 species, 20 strains each) were tested. Synergistic or antagonistic effects were observed in less than 1% of the tests performed; they appeared to represent method-dependent fluctuations rather than true antibiotic interactions. No significant differences among the five aminoglycosides tested were seen. Time-kill experiments performed with three representative strains of Escherichia coli and Serratia marcescens showed additive combination effects with respect to the kill rates and inhibition of bacterial regrowth. Exposure of Serratia strains to either ciprofloxacin or gentamicin before the addition of the second drug had little influence on the combination effects observed. No antagonistic drug interactions were seen in vivo when combination therapy with ciprofloxacin and gentamicin was evaluated in a model of E. coli thigh muscle infection in neutropenic mice. Comparable therapeutic effects were obtained, regardless of whether the two compounds were administered simultaneously or sequentially at 1- or 2-h intervals.