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The aim of this study was to investigate the in vitro activity of various antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates producing OXA-23 carbapenemases.In vitro activity of six two-drug combinations against CRAB isolates collected from patients with CRAB bacteremia was evaluated using the checkerboard method and time-kill assay [0.5 ×, 1 ×, 2 × minimum inhibitory concentrations (MIC)], to identify potential synergistic and bactericidal two-drug combinations against CRAB isolates, using meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam. All 10 CRAB isolates in our study carried the OXA-58-type and OXA-23-type carbapenem-hydrolyzing oxacillinase. The colistin-ceftolozane/tazobactam combination demonstrated a synergistic effect in both the time-kill assay (using an antibiotic concentration of 1 × MIC) and the checkerboard method, while simultaneously showing a bactericidal effect in the time-kill assay. For all 10 CRAB isolates, time-kill curves showed a significant synergistic bactericidal activity of the colistin-ceftolozane/tazobactam combination at 0.5 × MIC. Overall, there is substantial discordance of synergistic activity between the checkerboard microdilution and time-kill assay (with a concordance of 35%). Our study demonstrated that the two-drug combinations of colistin and ceftolozane/tazobactam can be a potential alternative for treating CRAB infections. The effect of these antibiotic combinations should be evaluated through clinical trials. |
