Activity of piperacillin/tazobactam in combination with amikacin, ciprofloxacin, and trovafloxacin against Pseudomonas aeruginosa by time-kill

Pseudomonal infections have a high rate of morbidity and mortality, thus combination therapy is often recommended. We compared the activity of piperacillin/tazobactam in combination with amikacin, ciprofloxacin, or trovafloxacin at different concentrations against P. aeruginosa using time- kill methodology. MICs were determined for 4 clinical isolates of P. aeruginosa. Time-kill studies were conducted over 24 h. Each drug was tested alone and in combination using the following concentrations: 2 and 1/4, 1/4 and 2, and 1/4 and 1/4 x MIC of piperacillin/tazobactam and amikacin, ciprofloxacin, or trovafloxacin. Combinations were classified as synergistic, indifferent, or antagonistic. Synergy was defined as ≥ 2-log₁₀ decrease in CFU/mL at 24 h with the combination when compared to the most active single agent and the number of surviving organisms for the antimicrobial combination was ≥2-log₁₀ less than the initial inoculum. The MICs for piperacillin/tazobactam, amikacin, ciprofloxacin, and trovafloxacin, ranged from 4/4-512/4, 0.5-4, 0.125-4, and 0.5-8 μg/mL, respectively. Fifty eight percent of the combinations using concentrations of 1/4 x MIC of piperacillin/tazobactam and 2 x MIC of amikacin, ciprofloxacin, and trovafloxacin or 2 x MIC of piperacillin/tazobactam and 1/4 x MIC of amikacin, ciprofloxacin, and trovafloxacin were synergistic. Although no differences existed in synergistic activity between the two combinations, the 1/4 and 2 x MIC maintained colony counts below the limit of quantification for 24 h for a significantly greater percentage of isolates than the 2 and 1/4 x MIC combinations (75 and 25%, respectively; p = 0.04). Overall, synergy was most frequently (42%) noted with the piperacillin/tazobactam and amikacin combinations followed by 33 and 8% of the piperacillin/tazobactam and trovafloxacin and ciprofloxacin combinations. No combination demonstrated antagonism. Further more extensive studies are necessary to determine clinical significance. (C) 2000 Elsevier Science Inc.