Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
BMC Infect Dis. 2011 Apr 27;11:109. doi: 10.1186/1471-2334-11-109.
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.
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.
鲍曼不动杆菌的广泛耐药性是临床环境中的一个严重问题。因此，寻找有效的抗生素联合治疗方案对于治疗由这种“超级细菌”引起的感染非常重要。在这项研究中，我们分析了三种粘菌素为基础的组合和一种米诺环素为基础的组合对临床分离的广泛耐药鲍曼不动杆菌（XDR-AB）菌株的体外活性。
收集了 14 株 XDR-AB 临床分离株。通过聚合酶链反应指纹分析确定克隆型。药敏试验按照临床和实验室标准协会的标准进行。采用时间杀伤研究，通过 12 小时平均生存时间（MST12 h）分析，对四种选定菌株的药物组合活性进行了研究。
时间杀伤研究表明，粘菌素（0.5 或 0.25μg/ml）的最低抑菌浓度（MIC）在 2 至 4 小时内完全杀死所有菌株，但 0.5×MIC 粘菌素没有杀菌活性。美罗培南（8μg/ml）、米诺环素（1μg/ml）或利福平（0.06μg/ml）没有杀菌活性。然而，粘菌素 0.5×MIC（0.25 或 0.125μg/ml）与上述药物的组合均具有协同作用，并对所有测试分离株显示出杀菌活性。美罗培南（16μg/ml）与米诺环素（0.5×MIC，4 或 2μg/ml）的组合对所有测试分离株均具有协同作用，但单独使用时均无杀菌活性。药物组合（粘菌素或米诺环素为基础的组合）的 MST12 h 值明显短于单一药物（p<0.01）。
本研究表明，粘菌素/美罗培南、粘菌素/利福平、粘菌素/米诺环素和米诺环素/美罗培南组合对 XDR-AB 菌株具有体外协同作用。
