In vitro Effects of Various Antimicrobials Alone and in Combinations against Imipenem-Resistant Pseudomonas aeruginosa

Imipenem-resistant Pseudomonas aeruginosa (IRPA) infection is a serious problem in hospitals. Combination therapy is an alternative treatment for this infection. In this study, the in vitro activities of amikacin, aztreonam, ceftazidime, ciprofloxacin, colistin, imipenem, and piperacillin/tazobactam alone and in various combinations were determined by E-test for 38 imipenem-resistant P. aeruginosa isolates obtained from a Thai hospital. Of the 38 IRPA isolates, 9 (24%) were low-level IRPA (defined as MICs of imipenem 8-32 μg/mL) and 29 (76%) were high-level IRPA (defined as MICs of imipenem >32 μg/mL). The high-level IRPA isolates were susceptible to colistin (90%), piperacillin/tazobactam (72%), and amikacin (52%). The low-level IRPA isolates were susceptible to colistin (100%) and all other antimicrobials tested (78%-89%). The MIC50 value of colistin against both the high-level and low-level IRPA isolates was 1.5 μg/mL. Of all the antimicrobial combinations tested, ceftazidime plus ciprofloxacin displayed the highest percentages of synergistic effects against IRPA isolates (26%, 10/38 isolates) and a high percentages of synergistic effects against high-level IRPA isolates (21, 6/29 isolates), with no antagonistic effects detected. Colistin had the greatest activity against most IRPA isolates among all of the antimicrobials tested, while ceftazidime plus ciprofloxacin showed promise in treating infections caused by IRPA isolates including high-level IRPAs.