Timed killing kinetic studies of the interaction between ciprofloxacin and beta-lactams against gram-negative bacilli

Timed killing kinetic studies were performed with ciprofloxacin in combination with aztreonam, ceftazidime, piperacillin/tazobactam, and ticarcillin/clavulanic acid against three isolates each of Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa. Each antimicrobial agent in the combination was tested at its MIC and at one-half and one-quarter of its MIC. Colony counts were determined at 0, 3, 5, and 7 hours. Synergy occurred most frequently at 7 hours and, when present, was most likely to occur when ciprofloxacin and the beta-lactam were tested at concentrations equal to their respective MICs. Synergy after 3 hours of incubation was not predictive of a synergestic interaction at 5 or 7 hours. Antagonism was noted in several instances, particularly when ciprofloxacin and the beta-lactam were combined at one-quarter of their respective MICs.