结核分枝杆菌对利福喷汀与利福平交叉耐药的实验研究

In vitro study on cross resistance of rifampin and rifapentine for Mycobacterium tuberculosis

目的观察利福喷汀对结核分枝杆菌的杀菌效力及其与利福平的交叉耐药性,探讨利福喷汀对结核分枝杆菌的实验室耐药界限,为临床应用利福喷汀治疗结核病,包括治疗对利福平耐药的结核病提供依据.方法用7H9液体培养基、苏通液体培养基、改良罗氏固体培养基测定利福喷汀和利福平对结核分枝杆菌标准株(H37Rv)及临床分离的利福平敏感株、利福平耐药株的最低抑菌浓度(MIC).结果在7H9液体培养基上对临床分离的19株利福平敏感株分别测定利福平和利福喷汀的MIC,有80%利福平敏感株利福平的MIC≥0.32 μg/ml,而利福喷汀的MIC多分布在0.02～0.32 μg/ml之间(占84%);无论标准株H37Rv、利福平敏感株(19株)或是利福平耐药株(45株),利福喷汀对结核分枝杆菌的MIC普遍比利福平低2～4倍;利福喷汀敏感株和耐药株的MIC差别较大,在MIC为5～10 μg/ml处能最大限度地区分敏感菌和耐药菌.结论利福喷汀与利福平存在着交叉耐药, 但利福喷汀比利福平有更强的杀菌效力,部分结核分枝杆菌对利福平达到临床耐药时,仍未达到利福喷汀临床耐药,对利福平耐药的部分结核分枝杆菌对利福喷汀仍具有一定程度的敏感性,提示临床上对利福平耐药的结核病患者使用利福喷汀可能有一定效果;实验结果对利福喷汀临界耐药界限进行了初步筛查,为利福喷汀常规药敏试验的开展提供了基本试验数据.

Objective To study the bactericidal effect of rifapentine and its cross-resistance with rifampin for Mycobacterium tuberculosis and to determine the critical concentration of rifapentine for laboratory drug susceptibility test and therefore to provide the laboratory data for using rifapentine in the treatment of tuberculosis, particularly rifampin resistant tuberculosis. Methods We detected the minimal inhibitory concentrations (MICs) of rifampin and rifapentine to H (37)Rv and isolated strains of rifampin susceptible and resistant Mycobacterium tuberculosis by using Middlebrook 7H9, Sauton and Lwenstein-Jensen media. Results The MICs of rifampin were ≥0.32 μg/ml for 80% of the 19 rifampin susceptible strains on Middlebrook 7H9 and the MICs of rifapentine ranged from 0.02 μg/ml to 0.32 μg/ml for most of the strains (84%). The MICs of rifapentine were 2-4 times lower than those of rifampin to H (37)Rv and most clinical isolates. The rifapentine susceptible isolates were mostly separated from resistant strains at MICs 5-10 (μg/ml). Conclusions Our results demonstrate the cross resistance of rifampin and rifapentine and the stronger bactericidal potency of rifapentine than rifampin. Some rifampin resistant strains still show susceptibility to rifapentine, which suggests rifapentine may be effective in the treatment of rifampin resistant tuberculosis. Our results also determined a critical resistant concentration of rifapentine for routine drug susceptibility test.