In vitro Evaluation of Proton Motive Force-Dependent Efflux Pumps Among Multidrug Resistant Acinetobacter baumannii Isolated From Patients at Tehran Hospitals

Background: Multidrug-resistant (MDR) strains of Acinetobacter baumannii have been increasingly reported as a major cause of nosocomial infections, and have created major therapeutic problems worldwide. Objectives: The aim of the present study was to evaluate the role of proton motive force (PMF)-dependent efflux mechanism in the multiple resistance phenotype of A. baumannii clinical strains. Materials and Methods: A total of 65 A. baumannii clinical strains were collected from hospitals in Tehran. These were tested for antimicrobial susceptibility using disc agar diffusion and broth microdilution methods. Active efflux was assessed by ethidium bromide accumulation assays. Further evaluations were performed by the determination of the minimum inhibitory concentrations and the accumulation of ciprofloxacin against selected MDR A. baumannii in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), an inhibitor of PMF. Results: Ninety five percent of strains were MDR, with high rate of resistance to ciprofloxacin (92.3%), gentamicin (89.2%), and ceftazidime (93.8%). Colistin and imipenem were the most effective antibiotics with resistance rates of 1.5% and 44.6%, respectively. MDR strains showed a four-fold reduction in the MIC of ciprofloxacin when tested in the presence of the efflux pump inhibitor (CCCP). The addition of CCCP led to a significant increase in the accumulation of ethidium bromide and ciprofloxacin. Conclusions: PMF-dependent efflux mechanism appears to play an important role in the MDR phenotype of A. baumannii clinical strains.