Activities of colistin- and minocycline-based combinations against extensive drug resistant Acinetobacter baumannii isolates from intensive care unit patients

Background: Extensive drug resistance of Acinetobacter baumannii is a serious problem in the clinical setting. It is therefore important to find active antibiotic combinations that could be effective in the treatment of infections caused by this problematic 'superbug'. In this study, we analyzed the in vitro activities of three colistin-based combinations and a minocycline-based combination against clinically isolated extensive drug resistant Acinetobacter baumannii (XDR-AB) strains. Methods: Fourteen XDR-AB clinical isolates were collected. The clonotypes were determined by polymerase chain reaction-based fingerprinting. Susceptibility testing was carried out according to the standards of the Clinical and Laboratory Standards Institute. Activities of drug combinations were investigated against four selected strains and analyzed by mean survival time over 12 hours (MST(12) (h)) in a time-kill study. Results: The time-kill studies indicated that the minimum inhibitory concentration (MIC) of colistin (0.5 or 0.25 mu g/mL) completely killed all strains at 2 to 4 hours, but 0.5xMIC colistin showed no bactericidal activity. Meropenem (8 mu g/mL), minocycline (1 mu g/mL) or rifampicin (0.06 mu g/mL) did not show bactericidal activity. However, combinations of colistin at 0.5xMIC (0.25 or 0.125 mu g/mL) with each of the above were synergistic and shown bactericidal activities against all test isolates. A combination of meropenem (16 mu g/mL) with minocycline (0.5xMIC, 4 or 2 mu g/mL) was synergitic to all test isolates, but neither showed bactericidal activity alone. The MST(12) (h) values of drug combinations (either colistin-or minocycline-based combinations) were significantly shorter than those of the single drugs (p < 0.01). Conclusions: This study indicates that combinations of colistin/meropenem, colistin/rifampicin, colistin/minocycline and minocycline/meropenem are synergistic in vitro against XDR-AB strains.