Frequency of embB codon 306 mutations in ethambutol-susceptible and -resistant clinical Mycobacterium tuberculosis isolates in Kuwait

Setting: Recent reports of embB306 mutations in ethambutol-resistant and ethambutol-susceptible drug-resistant strains of Mycobacterium tuberculosis have questioned the significance of these mutations in conferring resistance to ethambutot (EMB). Objective: To determine the occurrence of embB306 mutations in all EMB-resistant and susceptible drug-resistant M. tuberculosis strains isolated during a specified period at a single geographical location. Design: Twenty-five pansusceptible, all EMB-resistant and -susceptible M. tuberculosis strains resistant to other first-tine drugs isolated in Kuwait during 2000-2003 were analyzed. The embB306 mutations were detected by PCR-restriction fragment length polymorphism and DNA sequencing. The PCR-based methods were also used for determining strain relatedness. Results: None of the pansusceptible A tuberculosis strains contained a mutation at embB306. Fifteen of 50 (30%) EMB-resistant strains but only three of 122 (2%) EMB-susceptible isolates resistant to other first-Line drugs contained a mutated embB306. The EMB-susceptible isolates with embB306 mutation were resistant to isoniazid plus other drug(s). The isolates carrying similar mutations were genotypically distinct strains. Conclusions: The frequency of embB306 mutations in EMB-resistant strains compared to EMB-susceptible M. tuberculosis isolates resistant to other drugs was 15 times higher. Association of embB306 mutations in EMB-susceptible strains with isoniazid resistance and inherent problems associated with phenotypic EMB susceptibility testing suggest that these strains may actually be EMB-resistant. (c) 2006 Elsevier Ltd. ALL rights reserved.