Eight unrelated clinical Acinetobacter baumannii isolates resistant to all commonly used antibiotics were subjected to three-dimensional checkerboard microtiter plate dilution and time-kill studies at one-fourth of their MICs of polymyxin B, imipenem, and rifampin. Synergy was demonstrated with combinations of polymyxin B and imipenem, polymyxin B and rifampin, and polymyxin B, imipenem, and rifampin. Double combinations of polymyxin B and imipenem and of polymyxin B and rifampin were bactericidal for seven of eight isolates, and triple combinations were bactericidal for all isolates within 24 h. Future clinical studies using double and triple therapy with these antibacterials may provide an effective option against potentially lethal infection due to multiresistant Acinetobacter baumannii.In recent years, Acinetobacter baumannii has emerged as one of the more ubiquitous antibiotic-resistant gram-negative nosocomial pathogens among critically ill patients (4, 23). Although the carbapenems, ampicillin-sulbactam, and amikacin have retained excellent in vitro and clinical activities against susceptible strains of A. baumannii, a growing number of reports have documented resistance to these antibacterials (1, 2, 10, 12-14, 16). As a result nontraditional agents, including polymyxin B and colistin, have been used to treat patients infected with multiresistant A. baumannii (6, 9, 15). However, pulmonary infections have not responded well to such monotherapy, and resistance has occurred among strains that have persisted during treatment (6,15,24).In this communication, we describe the in vitro double and triple interactions of polymyxin B, imipenem, and rifampin against eight unique strains of multidrug-resistant A. baumannii using checkerboard microdilution and time-kill methods. MATERIALS AND METHODSEight multidrug-resistant clinical strains of A. baumannii were obtained from the Clinical Microbiology Laboratory at New York Hospital Queens. All isolates had different pulsed-field gel electrophoresis patterns and were considered unrelated according to the criteria established by Tenover et al. (21). MICs of selected individual antibiotics were then determined using microdilution and E-test methods (AB Biodisk North America Inc., Piscataway, N.J.) by the Infectious Disease Research Laboratory. E-test metallo-beta-lactamase (E-test MBL) strips were used to detect the presence of molecular class B beta-lactamases (25). Rifampin and polymyxin B were obtained from Sigma (St. Louis, Mo.), and imipenem powder was supplied by Merck and Co. (Rahway, N.J.). MIC determinations were performed using checkerboard microdilution methods with Mueller-Hinton broth and a final inoculum of approximately 5 ϫ 10 5 CFU/ml. Microdilution plates for evaluation of triple drug combinations were performed in the following manner. The first microtiter plate contained no imipenem and increasing concentrations of rifampin ranging from 0 to 32 g/ml on the x axis and increasing concentrations of polymyxin B ranging from 0 to 32 g/ml on the y axis. Ea...
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