Comparison of the bactericidal activity of ciprofloxacin alone and in combination with selected antipseudomonal β-lactam agents against clinical isolates of Pseudomonas aeruginosa

Abstract

The bactericidal activity of ciprofloxacin against 60 clinical isolates of Pseudomonas aeruginosa was evaluated by exposing replicating microorganisms to concentrations ranging from 0.12 to 2 μg/ml for 48 hr. In addition, ciprofloxacin was combined with selected antipseudomonal β-lactams using subinhibitory concentrations ( 1 4 × MIC , 1 2 × MIC ) of each. We found that a concentration of 2μg/ml of ciprofloxacin resulted in bactericidal activity (≥99.9% killing of the final inoculum) at 8 and 12 hr for the highest percentage of isolates (95 and 96.7%, respectively). At the breakpoint concentration (1 μg/ml), there was bactericidal activity against 81.7% of these isolates at 8 hr and 78.7% at 12 hr. By 24 and 48 hr, regrowth was frequently seen for concentrations of 1 and 2 μg/m (76.7 and 41.7%, respectively). This regrowth represented limited progression of resistance (4- to 16-fold increase in MICs) to ciprofloxacin without cross-resistance to other classes of antibiotics. The combinations containing ciprofloxacin and β-lactam agent were synergistic for isolates that were susceptible to both agents. Moreover, the combinations prevented the emergence of resistance to either drug.