embB306 Mutations as Molecular Indicators to Predict Ethambutol Susceptibility in Mycobacterium tuberculosis

被引：14

作者：

Sirgel, Frederick A. ^{[1
]}

Warren, Robin M. ^{[1
]}

Streicher, Elizabeth M. ^{[1
]}

Victor, Thomas C. ^{[1
]}

van Helden, Paul D. ^{[1
]}

Boettger, Erik C. ^{[2
,3
]}

机构：

[1] Univ Stellenbosch, Fac Hlth Sci, Div Mol Biol & Human Genet, DST NRF Ctr Excellence Biomed TB Res,MRC Ctr Mol, ZA-7505 Cape Town, South Africa

[2] Univ Zurich, Inst Med Mikrobiol, Zurich, Switzerland

[3] Univ Zurich, Natl Zentrum Mykobakterien, Zurich, Switzerland

来源：

CHEMOTHERAPY | 2012年 / 58卷 / 05期

基金：

英国医学研究理事会; 新加坡国家研究基金会;

关键词：

Antituberculosis drugs; Borderline resistance; Tuberculosis therapy; Mutations; Drug resistance; CODON; 306; MUTATIONS; DRUG-RESISTANCE;

D O I：

10.1159/000343474

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Discordant results in conventional susceptibility testing of ethambutol against Mycobacterium tuberculosis may lead to underreporting of drug resistance. Methods: A 240-bp region of the embB gene in 111 clinical isolates of M. tuberculosis was sequenced and examined for mutations linked to ethambutol resistance. The phenotypic susceptibility levels of the isolates were quantified by the BACTEC (TM) MGIT 960 (TM) TB System and correlated with the genotypic test results. These data were analyzed to find information that could be used to clarify discordant ethambutol susceptibility test results. Results: Mutations M306I (n = 56), M306V (n = 18) and M306L (n = 3) in M. tuberculosis showed decreased susceptibility to ethambutol. The minimum inhibitory concentrations (MICs) in 73% (56/77) of embB306 mutants were at or just above the critical concentration (MICs, 5.0 to <= 12.5 mu g/ml) of ethambutol reflecting borderline (or intermediate) resistance. Eight ethambutol-resistant isolates lacked embB mutations, probably due to mutational alterations elsewhere in the genome. Conclusion: Our findings suggest that clinical isolates containing embB306 mutations with MICs overlapping the critical concentration are associated with discordant ethambutol susceptibility test results. The clinical significance of borderline resistance in combination treatment of tuberculosis remains to be determined before alternative ethambutol breakpoints are considered. Copyright (c) 2012 S. Karger AG, Basel

引用

页码：358 / 363

页数：6

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