利奈唑胺联合米诺环素对万古霉素耐药肠球菌的抗菌活性。

Antimicrobial activity of linezolid combined with minocycline against vancomycin-resistant Enterococci.

机构信息

Department of Clinical Laboratory, First Hospital of Fangshan District, Beijing, China.

出版信息

Chin Med J (Engl). 2013 Jul;126(14):2670-5.

Abstract

BACKGROUND

Vancomycin-resistant Enterococci (VRE) cause serious infections that are difficult to treat. We carried out this study to determine the mutant prevention concentration (MPC) of linezolid when combined with minocycline against VRE strains, to determine the mechanism of drug resistance in vitro, and to provide a theoretical basis for the rational use of drugs against VRE.

METHODS

The minimum inhibitory concentrations (MICs) of linezolid and minocycline against 30 Enterococci (E.) isolates (including 20 VRE strains) were determined by the broth microdilution method. Drug interactions were assessed by the checkerboard microdilution tests and confirmed by time-kill studies. Two vancomycin-susceptible strains N27 and N40 (linezolid MIC, 2 g/ml; minocycline MIC, 4 µg/ml) and control strains E. faecalis ATCC 29212 and ATCC 51299 were also tested. The MPCs of linezolid and minocycline (alone and combined) were determined using the agar dilution method. Strains showing stable resistance were analyzed by polymerase chain reaction (PCR) amplification of domain V of the 23S rRNA gene.

RESULTS

Checkerboard titration studies revealed synergistic effects of combination therapy in 26.7% of 30 E. isolates. Antagonism was not observed. The G2576U mutation was detected in stable linezolid-resistant strains of ATCC 29212, N40, and N27 before and after resistance screening, and MIC values increased with the number of G2576U mutations. The MPC of linezolid against E. decreased dramatically when combined with minocycline, and vice versa.

CONCLUSION

Linezolid or minocycline alone produce resistant strains; however, their joint use may reduce the MPC of each agent against VRE, thereby decreasing resistant mutants and bacterial infections.

摘要

背景

耐万古霉素肠球菌（VRE）可引起难以治疗的严重感染。我们进行了这项研究，以确定利奈唑胺联合米诺环素对 VRE 株的突变预防浓度（MPC），确定体外耐药机制，并为合理使用抗 VRE 药物提供理论依据。

方法

采用肉汤微量稀释法测定 30 株肠球菌（E.）分离株（包括 20 株 VRE 株）对利奈唑胺和米诺环素的最小抑菌浓度（MIC）。通过棋盘微量稀释试验评估药物相互作用，并通过时间杀伤研究进行确认。还测试了两株万古霉素敏感株 N27 和 N40（利奈唑胺 MIC，2 g/ml；米诺环素 MIC，4 µg/ml）和对照株 E. faecalis ATCC 29212 和 ATCC 51299。采用琼脂稀释法测定利奈唑胺和米诺环素（单独和联合）的 MPC。通过聚合酶链反应（PCR）扩增 23S rRNA 基因结构域 V 分析显示稳定耐药的菌株。

结果

棋盘滴定研究显示，30 株 E. 分离株中有 26.7%表现出联合治疗的协同作用。未观察到拮抗作用。在 ATCC 29212、N40 和 N27 的稳定利奈唑胺耐药株中，在耐药筛选前后均检测到 G2576U 突变，MIC 值随 G2576U 突变数量的增加而增加。利奈唑胺与米诺环素联合使用时，对 E. 的 MPC 显著降低，反之亦然。