In vitro effects of combinations of antipseudomonal agents against seven strains of multidrug-resistant Pseudomonas aeruginosa

Objectives: The aim of this study was to evaluate the combined effects of antibiotic combinations by agar incorporation inhibitory tests and by time-kill tests on seven geographically and epidemiologically distinct isolates of multidrug-resistant Pseudomonas aeruginosa. All seven strains were resistant to piperacillin, meropenem, ceftazidime, cefoperazone-sulbactam, aztreonam, amikacin and ciprofloxacin. Methods: Strains were distinguished by pulsed-field gel electrophoresis after DNA extraction and restriction with SpeI. MICs of the seven antibiotics listed above were determined by agar dilution. The effect of combinations of these agents was determined by agar incorporation tests and by time-kill studies. Results: Among the two-drug combinations, the combination aztreonam and amikacin was the most effective, inhibiting proliferation in five of the seven strains. Among the three-drug combinations, the combinations of piperacillin, ceftazidime and amikacin, and that of ceftazidime, aztreonam and amikacin were the most effective, inhibiting proliferation in all seven strains. In the killing tests, the three-drug combination of ceftazidime, aztreonam and amikacin was the most effective. This three-drug combination had bacteriostatic effects on all seven strains 2, 4, 6 and 24 h after drug addition, synergic effects on 2-3 strains and bactericidal effects on 1-2 strains after 4, 6 and 24 h. Conclusions: The three-drug combination of ceftazidime, aztreonam and amikacin may be effective against P. aeruginosa resistant to all commonly used antipseudomonal drugs, and deserves further study.