利奈唑胺对分枝杆菌体外抑菌作用的初步研究

目的 评价利奈唑胺对MTB和5种非结核分枝杆菌(NTM)的体外抑菌作用,探讨利奈唑胺与其他抗结核药物联合使用时的体外相互作用.方法 采用微孔板Alamar Blue法测定利奈唑胺对MTB临床株121株、NTM临床菌株30株及相应标准菌株的MIC,观察利奈唑胺与7种常用抗结核药物联合使用时,对H37Rv和8株MTB 临床分离株的MIC值的影响,通过计算分级抑菌浓度指数,观察利奈唑胺与其他抗结核药物联合使用时是否存在协同作用.结果 94.2%(114/121)的MTB临床分离株可被≤1 mg/L的利奈唑胺抑制生长,利奈唑胺对敏感和MDR菌株及其他形式的耐药菌株的MIC差异无统计学意义(X2=0.481,P＞0.05).若以＞1 mg/L作为耐药标准,则5种NTM菌株中仅堪萨斯分枝杆菌对利奈唑胺敏感,脓肿分枝杆菌和偶然分枝杆菌均对利奈唑胺全耐药,鸟分枝杆菌和胞内分枝杆菌对利奈唑胺部分敏感.利奈唑胺与7种抗结核药物在体外联合使用时未表现出相关性.结论 利奈唑胺有很好的抗MTB活性,且与细菌对其他药物是否耐药无关.利奈唑胺对堪萨斯分枝杆菌有很好的抗菌活性,与其他常用抗结核药物联合使用时未表现出相关性.

Abstract：

Objective To evaluate the mycobactericidal efficacy of linezolid to Mycobacterium tuberculosis bacilli and Non-tuberculous mycobacteria ( NTM ) in vitro, and to analyze the interaction between linezolid and other anti-TB drugs in vitro.Methods The minimum inhibition concentrations (MICs) of 121 Mycobacterium tuberculosis clinical isolates and 30 non tuberculousis Mycobacteria isolates and the corresponding standard strains to linezolid were tested by Microplate Alamar Blue assay (MABA).The interactions between linezolid and rifampicin, isoniazid, streptomycin, ethambutol, kanamycin, ofloxacin,and rifabutin were also tested in vitro by fractional inhibitory concentration index ( FICI ) method.Results 94.2% ( 114/121 ) of the Mycobacterium tuberculosis isolates were inhibited by linezolid at concentrations ≤1 mg/L.There was no statistical difference in the MIC values of sensitive strains, MDR strains, and drug resistant strains other than MDR ( x2 = 0.481, P ＞0.05 ).Only Mycobacterium kansasii was totally sensitive to linezolid among the 5 tested NTM strains.In vitro drug combination testing displayed overall non-association between linezolid and 7 other anti-TB drugs among 8 clinical isolates and H37 Ry.Conclusions Linezolid showed great mycobactericidal efficacy to Mycobacterium tuberculosis clinical isolates in vitro,regardless of the strains' drug resistant parameters.This study also showed non-association of the interactions between linezolid and 7 other anti-TB drugs in vitro.

Evaluation of the mycobactericidal efficacy of linezolid in vitro

Objective To evaluate the mycobactericidal efficacy of linezolid to Mycobacterium tuberculosis bacilli and Non-tuberculous mycobacteria ( NTM ) in vitro, and to analyze the interaction between linezolid and other anti-TB drugs in vitro.Methods The minimum inhibition concentrations (MICs) of 121 Mycobacterium tuberculosis clinical isolates and 30 non tuberculousis Mycobacteria isolates and the corresponding standard strains to linezolid were tested by Microplate Alamar Blue assay (MABA).The interactions between linezolid and rifampicin, isoniazid, streptomycin, ethambutol, kanamycin, ofloxacin,and rifabutin were also tested in vitro by fractional inhibitory concentration index ( FICI ) method.Results 94.2% ( 114/121 ) of the Mycobacterium tuberculosis isolates were inhibited by linezolid at concentrations ≤1 mg/L.There was no statistical difference in the MIC values of sensitive strains, MDR strains, and drug resistant strains other than MDR ( x2 = 0.481, P ＞0.05 ).Only Mycobacterium kansasii was totally sensitive to linezolid among the 5 tested NTM strains.In vitro drug combination testing displayed overall non-association between linezolid and 7 other anti-TB drugs among 8 clinical isolates and H37 Ry.Conclusions Linezolid showed great mycobactericidal efficacy to Mycobacterium tuberculosis clinical isolates in vitro,regardless of the strains' drug resistant parameters.This study also showed non-association of the interactions between linezolid and 7 other anti-TB drugs in vitro.