In vitro double and triple synergistic activities of Polymyxin B, imipenem, and rifampin against multidrug-resistant Acinetobacter baumannii

Abstract

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.

FIG. 1.

(A) Three-dimensional isobologram for A. baumannii isolate A. The areas on the isobologram showing depressions (concave sinks) that approach zero represent the greatest synergy (ΣFIC ≤ 1.0). (B) Results for isolate B.

FIG. 2.

Time-kill experiments using one-fourth the MIC of each agent (0.25 μg of polymyxin B/ml, 0.5 μg of rifampin/ml, and 8.0 μg of imipenem/ml) alone and in combination for isolates A, B, E, and H. The dotted lines indicate the lower limit of detection of 2 log₁₀ CFU/ml.