Epidemiology of isoniazid resistance mutations and their effect on tuberculosis treatment outcomes.
نویسندگان
چکیده
Isoniazid resistance is highly prevalent in Vietnam. We investigated the molecular and epidemiological characteristics and the association with first-line treatment outcomes of the main isoniazid resistance mutations in Mycobacterium tuberculosis in codon 315 of the katG and in the promoter region of the inhA gene. Mycobacterium tuberculosis strains with phenotypic resistance to isoniazid from consecutively diagnosed smear-positive tuberculosis patients in rural Vietnam were subjected to Genotype MTBDRplus testing to identify katG and inhA mutations. Treatment failure and relapse were determined by sputum culture. In total, 227 of 251 isoniazid-resistant strains (90.4%) had detectable mutations: 75.3% in katG codon 315 (katG315) and 28.2% in the inhA promoter region. katG315 mutations were significantly associated with pretreatment resistance to streptomycin, rifampin, and ethambutol but not with the Beijing genotype and predicted both unfavorable treatment outcome (treatment failure or death) and relapse; inhA promoter region mutations were only associated with resistance to streptomycin and relapse. In tuberculosis patients, M. tuberculosis katG315 mutations but not inhA mutations are associated with unfavorable treatment outcome. inhA mutations do, however, increase the risk of relapse, at least with treatment regimens that contain only isoniazid and ethambutol in the continuation phase.
منابع مشابه
Isoniazid MIC and KatG Gene Mutations among Mycobacterium tuberculosis Isolates in Northwest of Iran
Objective(s) Isoniazid (INH) is one of the main first line drugs used in treatment of tuberculosis and development of resistance against this compound can result in serious problems in treatment procedures. Resistance to INH is mediated mainly by mutation in KatG gene that is coded for the catalase enzyme. The proportional method for detection of INH-resistance is time consuming due to the slo...
متن کاملCharacterization of Mutations in the Rpob and Katg Gene of Mycobacterium Tuberculosis Isolates From Pasteur Institute of Tehran
Objective: The Rifampicin resistance and susceptibility of Mycobacterium tuberculosis are caused by mutations in the 81-base pair region of the rpoB gene encoding the b-subunit of RNA polymerase. Methods: Isoniazid resistance of M. tuberculosis is related to mutations in inha , oxyR and ahpC genes which 30 to 90 percent of Isoniazid resistance is occurred in 3015 codons of kat...
متن کاملCharacterization of Mutations in the Rpob and Katg Gene of Mycobacterium Tuberculosis Isolates From Pasteur Institute of Tehran
Objective: The Rifampicin resistance and susceptibility of Mycobacterium tuberculosis are caused by mutations in the 81-base pair region of the rpoB gene encoding the b-subunit of RNA polymerase. Methods: Isoniazid resistance of M. tuberculosis is related to mutations in inha , oxyR and ahpC genes which 30 to 90 percent of Isoniazid resistance is occurred in 3015 codons of kat...
متن کاملتشخیص موتاسیون در کدون 315 ژن katG، مارکر مقاومت به ایزونیازید در سوش‌های مایکوباکتریوم توبرکولوزیس جدا شده از بیماران اصفهان و تهران با روش PCR-RFLP
Background and Objective: Drug resistance to tuberculosis is continuously increasing and is a significant threat to tuberculosis control programs because afew effective drugs are present against Mycobacterium tuberculosis. Although isoniazid (INH) is the most effective drug against tuberculosis, resistance to this drug also develops readily. Mutations in katG, specially the Ser315Thr substituti...
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عنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 57 8 شماره
صفحات -
تاریخ انتشار 2013