Ethionamide cross-and co-resistance in children with isoniazid-resistant tuberculosis

Schaaf H.S.
Victor T.C.
Venter A.
Brittle W.
Jordaan A.M.
Hesseling A.C.
Marais B.J.
Van Helden P.D.
Donald P.R.
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BACKGROUND: Ethionamide (ETH) is a structural analogue of isoniazid (INH). Both are pro-drugs requiring activation by separate and common enzyme pathways, which could lead to co-and/or cross-resistance. OBJECTIVE: To characterise paediatric INH-resistant mycobacterial isolates to investigate the presence of ETH resistance and mutations in the katG gene and the inhA promoter region. METHODS: Forty-fi ve INH-resistant and 19 INHs usceptible Mycobacterium tuberculosis control isolates from children from the Western Cape Province, South Africa, were analysed to quantify INH minimal inhibitory concentration, test for ETH resistance and investigate mutations in the katG gene and/or inhA promoter region. RESULTS: Among 45 INH-resistant children, ETH resistance was present in 19 of 39 (49%). An inhA promoter mutation was identifi ed in 15 (33.3%); 12/14 (86%) of these isolates were also ETH-resistant. Of the 21 isolates with a katG mutation, six (29%) were ETH-resistant. No isolate had both katG and inhA promoter mutations. Nine (20%) isolates had neither inhA promoter nor katG mutations. Of 15 isolates with inhA promoter mutation, 14 (93%) displayed low-or intermediate-level INH resistance. Among the 19 INH-susceptible isolates, ETH resistance was present in 1/18 (6%) and none showed inhA or katG gene mutations. CONCLUSION: We found a high level of cross-and coresistance with ETH among INH-resistant M. tuberculosis isolates from children in this geographic area. © 2009 The Union.
ethionamide, isoniazid, bacterial protein, catalase, InhA protein, Mycobacterium, katG protein, Mycobacterium tuberculosis, oxidoreductase, tuberculostatic agent, antibiotic resistance, article, bacterial gene, bacterium isolate, child, clinical article, cross resistance, gene mutation, human, infant, inhA gene, katG gene, minimum inhibitory concentration, Mycobacterium, pediatrics, preschool child, priority journal, promoter region, South Africa, tuberculosis, case control study, drug combination, drug effect, genetics, genotype, microbiological examination, microbiology, multidrug resistance, multidrug resistant tuberculosis, mutation, Mycobacterium tuberculosis, pathogenicity, phenotype, prospective study, treatment failure, Antitubercular Agents, Bacterial Proteins, Case-Control Studies, Catalase, Child, Child, Preschool, Drug Resistance, Multiple, Bacterial, Drug Therapy, Combination, Ethionamide, Genotype, Humans, Infant, Isoniazid, Microbial Sensitivity Tests, Mutation, Mycobacterium tuberculosis, Oxidoreductases, Phenotype, Promoter Regions, Genetic, Prospective Studies, South Africa, Treatment Failure, Tuberculosis, Multidrug-Resistant
International Journal of Tuberculosis and Lung Disease