耐多药结核分枝杆菌对利福布汀和利福平的交叉耐药性研究

发布时间：2019-03-13 14:20

【摘要】：利福平是治疗结核病的主选药物之一,随着它在临床上的广泛应用,耐药情况日渐严重。近年来耐多药结核病(multidrug resistant tuberculosis, MDR-TB)和广泛耐药结核病(extensive drug resistant tuberculosis, XDR-TB)已成为结核病控制中亟待解决的问题。利福布汀是近年来出现的利福霉素类新药,对结核分枝杆菌(Mycobacterium tuberculosis, MTB)及非结核分枝杆菌(non-tuberculous Mycobacterium, NTM),特别是对鸟-胞内分枝杆菌具有较强的活性。本研究希望通过对耐多药结核分枝杆菌临床分离株进行利福布汀和利福平交叉耐药性研究,为利福布汀治疗MDR-TB提供依据。 目的对耐多药结核分枝杆菌临床分离株进行利福布汀和利福平交叉耐药性研究分析,为利福布汀治疗MDR-TB提供依据。 方法2009年6月至2011年1月上海市肺科医院收治的痰培养阳性的肺结核患者,全部培养阳性菌株经菌种鉴定为结核分枝杆菌后采用BACTEC960测试其对7种抗结核药物(异烟肼、利福平、氧氟沙星、链霉素、乙胺丁醇、阿米卡星和卷曲霉素)的耐药性。随机筛选99株耐多药结核分枝杆菌临床分离株,在96孔板上检测利福布汀和利福平对99株耐多药菌株的90%最低抑菌浓度(MIC9o)。分析利福布汀对耐多药结核分枝杆菌临床分离株的的抗菌活性。交叉耐药率数据分析采用X2检验,两组的MIC比较采用的是经对数转化后行独立样本t检验进行统计学处理。 结果利福布汀和利福平交叉耐药率85.9%(85/99)。利福布汀的MIC9o值为≤16mg/L,中位数为2mg/L；利福平的MIC90值为≥2mg/L,中位数32mg/L,前者仅为后者的1/8-1/32。低耐利福平组和中耐利福平组的交叉耐药例数分别为0/9、5/9,而高耐利福平组几乎全部交叉耐药(98.8%,80/81),利福布汀和利福平的交叉耐药率随利福平的耐药程度加大而上升。利福布汀和利福平的交叉耐药率与耐药谱无相关性(x2=2.47,P=0.799)。 结论利福布汀对耐多药MTB有一定的抗菌活性,可作为治疗耐多药结核病的备选药物。
[Abstract]:Rifampicin is one of the primary drugs for the treatment of tuberculosis. With its wide application in clinical practice, the drug resistance is becoming more and more serious. In recent years, multidrug-resistant tuberculosis (multidrug resistant tuberculosis, MDR-TB) and extensively drug-resistant tuberculosis (extensive drug resistant tuberculosis, XDR-TB) have become urgent problems in tuberculosis control. Rifampicin is a new drug of rifamycin, which has strong activity against Mycobacterium tuberculosis (Mycobacterium tuberculosis, MTB) and non-tuberculous mycobacterium (non-tuberculous Mycobacterium, NTM),). The aim of this study was to provide evidence for rifampicin in the treatment of MDR-TB by cross-resistance of rifampin and rifampicin in clinical isolates of multidrug-resistant Mycobacterium tuberculosis. Aim to study the cross-resistance of rifampicin and rifampicin in clinical isolates of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) in order to provide evidence for rifampicin in the treatment of MDR-TB. Methods from June 2009 to January 2011, all the positive sputum culture strains were identified as Mycobacterium tuberculosis and tested by BACTEC960 for 7 antituberculosis drugs (isoniazid, rifampicin, ioniazid, rifampin). Drug resistance to ofloxacin, streptomycin, ethambutol, amikacin and crocicomycin. 99 clinical isolates of multidrug-resistant Mycobacterium tuberculosis were randomly screened. The 90% minimal inhibitory concentration (MIC9o) of rifampicin and rifampicin against 99 multidrug-resistant strains was detected on 96-well plate. To analyze the antibacterial activity of rifampicin against multi-drug-resistant clinical isolates of Mycobacterium tuberculosis. The data of cross-resistance rate was analyzed by X2 test, and the MIC of the two groups was compared by independent sample t-test after logarithmic transformation. Results the cross-resistance rate of rifampicin and rifampicin was 85.9% (85 / 99). The MIC9o value of rifampicin was 鈮，

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