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结核病患者中对利福平敏感的结核分枝杆菌分离株的异烟肼耐药情况。

Isoniazid resistance among rifampicin-susceptible Mycobacterium tuberculosis isolates from tuberculosis patients.

作者信息

Arora Jyoti, Singhal Ritu, Verma Ajoy Kumar, Kumar Gavish, Bhalla Manpreet, Sarin Rohit, Myneedu Vithal Prasad

机构信息

Department of Microbiology, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India.

Department of Microbiology, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India.

出版信息

Int J Mycobacteriol. 2016 Dec;5 Suppl 1:S127-S128. doi: 10.1016/j.ijmyco.2016.10.007. Epub 2016 Oct 27.

DOI:10.1016/j.ijmyco.2016.10.007
PMID:28043503
Abstract

OBJECTIVE/BACKGROUND: With the introduction of novel molecular techniques that rely on rifampicin (RIF) susceptibility, resistance to isoniazid (INH) or other first-line drugs remains undetected. Such patients are prescribed first-line antituberculosis therapy and are on RIF monodrug therapy during the continuation phase, which may lead to therapeutic failure and emergence of multidrug resistance. We aimed to study INH resistance among RIF-susceptible Mycobacterium tuberculosis (MTB) isolates from retreatment patients.

METHODS

The Drug Susceptibility Testing data for four first-line drugs (streptomycin [SM], INH, RIF, and ethambutol [EMB]) using BACTEC MGIT 960 (Becton Dickinson, Franklin 124 Lakes, NJ ,USA) and for two drugs (INH and RIF) using line probe assay was analyzed retrospectively at the Department of Microbiology, National Institute of Tuberculosis and Respiratory Diseases (New Delhi, India).

RESULTS

We analyzed 4910 drug susceptibility results performed using the BACTEC MGIT960 liquid culture system from 2009 to 2015. We found that 969 (19.7%) isolates were sensitive to all four first-line drugs, 3941 (80.3%) isolates were resistant to one or more drugs, and 3041 (61.9%) isolates were resistant to both RIF and INH with or without resistance to any other drug (multidrug resistant). Monodrug resistance to SM and EMB was observed in 94 (1.9%) and 8 (0.16%) isolates, respectively. RIF resistance without INH resistance was observed in 22 (0.44%) isolates. There were 776 isolates sensitive to RIF, but resistant to INH. Among these, INH resistance with EMB and/or SM was observed in 367 (7.47%) isolates, whereas 409 (8.3%) isolates were resistant to INH alone. The results of line probe assay from 2012 to 2015 were also analyzed, and the resistance to INH alone among all isolates with valid results was found to be 9.32% (1462/15,676). More than 75% of these isolates harbor mutations in the kat G gene associated with high-level resistance.

CONCLUSION

INH resistance among RIF-susceptible isolates was present in 10-15% of the total cases. Among these cases, the use of RIF susceptibility alone will fail to detect INH resistance. Since higher rates of failure, relapse, or acquired resistance are linked with INH resistance, rollout of techniques focusing on RIF resistance must, therefore, be accompanied by strict monitoring for better management of patients.

摘要

目的/背景:随着依赖利福平(RIF)敏感性的新型分子技术的引入,对异烟肼(INH)或其他一线药物的耐药性仍未被检测到。此类患者接受一线抗结核治疗,在继续治疗阶段接受利福平单药治疗,这可能导致治疗失败和多重耐药的出现。我们旨在研究复治患者中对利福平敏感的结核分枝杆菌(MTB)分离株对异烟肼的耐药情况。

方法

在印度新德里国家结核病和呼吸系统疾病研究所微生物学系,回顾性分析了使用BACTEC MGIT 960(美国新泽西州富兰克林湖124号路贝克顿·迪金森公司)检测四种一线药物(链霉素[SM]、异烟肼、利福平、乙胺丁醇[EMB])以及使用线性探针检测两种药物(异烟肼和利福平)的药敏试验数据。

结果

我们分析了2009年至2015年使用BACTEC MGIT960液体培养系统进行的4910次药敏试验结果。我们发现,969株(19.7%)分离株对所有四种一线药物敏感,3941株(80.3%)分离株对一种或多种药物耐药,3041株(61.9%)分离株对利福平和异烟肼均耐药,无论是否对其他任何药物耐药(多重耐药)。分别有94株(1.9%)和8株(0.16%)分离株对链霉素和乙胺丁醇单药耐药。22株(0.44%)分离株对利福平耐药但对异烟肼不耐药。有776株对利福平敏感但对异烟肼耐药。其中,367株(7.47%)分离株对异烟肼耐药且对乙胺丁醇和/或链霉素耐药,而409株(8.3%)分离株仅对异烟肼耐药。还分析了2012年至2015年线性探针检测的结果,在所有有有效结果的分离株中,仅对异烟肼的耐药率为9.32%(1462/15676)。这些分离株中超过75%在与高水平耐药相关的kat G基因中存在突变。

结论

在所有病例中,10%-15%的对利福平敏感的分离株对异烟肼耐药。在这些病例中,仅使用利福平敏感性检测将无法检测到异烟肼耐药。由于较高的治疗失败、复发或获得性耐药率与异烟肼耐药有关,因此,在推广针对利福平耐药的技术时,必须同时进行严格监测,以便更好地管理患者。

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