In vitro Effects of Combined Antibiotics against Multidrug-resistant Pseudomonas aeruginosa

Background/Aims: The inhibitory effects of the combination of -lactam with ciprofloxacin or amikacin against clinical isolates of multidrug-resistant Pseudomonas aeruginosa were evaluated. Methods: This study examined ten isolates with variable levels of resistance to ceftazidime, cefepime, piperacillin/tazobactam, meropenem, ciprofloxacin, and amikacin. The efficacy of the combined antibiotics was studied using a checkerboard method or in vitro killing assay. Results: The combination of ceftazidime, cefepime, aztreonam, piperacillin-tazobactam, or meropenem with amikacin showed synergistic effects for all of the strains regardless of the minimum inhibitory concentration (MIC) of amikacin, but combination with ciprofloxacin showed a synergistic effect for the isolate with a low MIC of ciprofloxacin by the checkerboard method. The isolates with a high MIC of ciprofloxacin showed an indifferent effect in combination with -lactam and ciprofloxacin. The in vitro killing assay showed that meropenem with ciprofloxacin acted synergistically for the isolates with a MIC of 16 /mL of ciprofloxacin. However, amikacin showed synergistic effects with meropenem for the isolates with high-level resistance against amikacin, i.e., up to an MIC of 128 /mL. Contrary to the checkerboard method results, no synergy was observed for the combination of ceftazidime/piperacillin-tazobactam and amikacin. Conclusions: Meropenem with amikacin can be the first choice for infections caused by multidrug-resistant P. aeruginosa when the level of resistance is not known.