Epidemiology of Isoniazid Resistance Mutations and Their Effect on Tuberculosis Treatment Outcomes

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 inMycobacterium tuberculosis in codon 315 of the katG and in the promoter region of the inhA gene.Mycobacterium tuberculosis strains with phenotypic resis-tance to isoniazid from consecutively diagnosed smear-positive tuberculosis patients in rural Vietnamwere subjected to Geno-typeMTBDRplus testing to identify katG and inhAmutations. Treatment failure and relapse were determined by sputum cul-ture. 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 streptomy-cin, rifampin, and ethambutol but not with the Beijing genotype and predicted both unfavorable treatment outcome (treatment failure or death) and relapse; inhA promoter regionmutations were only associated with resistance to streptomycin and relapse. In tuberculosis patients,M. tuberculosis katG315 mutations but not inhAmutations are associated with unfavorable treatment outcome. inhAmutations do, however, increase the risk of relapse, at least with treatment regimens that contain only isoniazid and ethambutol in the continuation phase. With 8.8 million cases notified and 1.4 million deaths in 2010,tuberculosis (TB) remains a major burden to global health (1). In addition to rifampin, isoniazid is an important drug in first-line anti-TB treatment (2). Mycobacterium tuberculosi