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

Abstract

ABSTRACTIsoniazid 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 tuberculosisin codon 315 of thekatGand in the promoter region of theinhAgene.Mycobacterium tuberculosisstrains with phenotypic resistance to isoniazid from consecutively diagnosed smear-positive tuberculosis patients in rural Vietnam were subjected to Genotype MTBDRplustesting to identifykatGandinhAmutations. Treatment failure and relapse were determined by sputum culture. In total, 227 of 251 isoniazid-resistant strains (90.4%) had detectable mutations: 75.3% inkatGcodon 315 (katG315) and 28.2% in theinhApromoter region.katG315mutations 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;inhApromoter region mutations were only associated with resistance to streptomycin and relapse. In tuberculosis patients,M. tuberculosiskatG315mutations but notinhAmutations 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.