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

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 (MST12 h) in a time-kill study.The time-kill studies indicated that the minimum inhibitory concentration (MIC) of colistin (0.5 or 0.25 μg/mL) completely killed all strains at 2 to 4 hours, but 0.5×MIC colistin showed no bactericidal activity. Meropenem (8 μg/mL), minocycline (1 μg/mL) or rifampicin (0.06 μg/mL) did not show bactericidal activity. However, combinations of colistin at 0.5×MIC (0.25 or 0.125 μg/mL) with each of the above were synergistic and shown bactericidal activities against all test isolates. A combination of meropenem (16 μg/mL) with minocycline (0.5×MIC, 4 or 2 μg/mL) was synergitic to all test isolates, but neither showed bactericidal activity alone. The MST12 h values of drug combinations (either colistin- or minocycline-based combinations) were significantly shorter than those of the single drugs (p < 0.01).This study indicates that combinations of colistin/meropenem, colistin/rifampicin, colistin/minocycline and minocycline/meropenem are synergistic in vitro against XDR-AB strains.Nosocomial infections caused by drug-resistant Acinetobacter baumannii are a major global problem [1]. Recent data from the Chinese Network for Bacterial-resistance Surveillance demonstrated that the susceptibility of A. baumannii to carbapenems has decreased to below 50%, and almost 17% of these isolates are resistant to all antimicrobial agents that are routinely used in clinical practice [2]. Unfortunately, no new antibiotics will be available for extensive drug resistant (XDR) gram-negative pathogens including A. baumannii for at least a decade [3]. These data highlight the importance and