In vitro synergistic antimicrobial activity of a combination of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam against carbapenem-resistant Acinetobacter baumannii

Abstract

We investigated the in vitro activity of various antimicrobial combinations against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. The in vitro activity of six two-drug combinations against CRAB isolates collected from the blood samples of patients with bloodstream infection was evaluated using the checkerboard method and time-kill assay [0.5 x, 1 x, and 2 x minimum inhibitory concentration (MIC)] to identify potential synergistic and bactericidal two-drug combinations against CRAB isolates. The effects of meropenem, colistin, tigecycline, rifampin, and ceftolozane/tazobactam combinations were investigated. All 10 CRAB isolates in our study produced the OXA-58-type and OXA-23-type carbapenem-hydrolyzing oxacillinases. The colistin-ceftolozane/tazobactam combination showed synergistic effects in both the time-kill assay (using an antibiotic concentration of 1 x MIC) and the checkerboard method. It also showed bactericidal effects in the time-kill assay. For all 10 CRAB isolates, time-kill curves showed synergistic bactericidal activity of the colistin-ceftolozane/tazobactam combination at 0.5 x MIC. Overall, there was substantial discordance of synergistic activity between the checkerboard microdilution and time-kill assays (with a concordance of 31.7%). Our study demonstrated that two-drug combinations of colistin and ceftolozane/tazobactam could be useful treatment alternatives for CRAB infections. The effects of these antibiotic combinations should be evaluated using in vivo experimental models.