Desmond Tutu Tuberculosis Centre, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg Children's Hospital, Tygerberg, South Africa.
Int J Tuberc Lung Dis. 2009 Nov;13(11):1355-9.
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.
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.
Forty-five INH-resistant and 19 INH-susceptible 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.
Among 45 INH-resistant children, ETH resistance was present in 19 of 39 (49%). An inhA promoter mutation was identified 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.
We found a high level of cross- and co-resistance with ETH among INH-resistant M. tuberculosis isolates from children in this geographic area.
乙硫异烟胺（ETH）是异烟肼（INH）的结构类似物。两者都是前药，需要通过单独和共同的酶途径激活，这可能导致共同和/或交叉耐药性。
对儿童中 INH 耐药的分枝杆菌分离株进行特征描述，以研究 ETH 耐药性的存在以及 katG 基因和 inhA 启动子区域的突变情况。
对来自南非西开普省的儿童中的 45 株 INH 耐药和 19 株 INH 敏感的结核分枝杆菌对照分离株进行分析，以定量 INH 最小抑菌浓度，检测 ETH 耐药性，并研究 katG 基因和/或 inhA 启动子区域的突变情况。
在 45 例 INH 耐药的儿童中，39 例（49%）中存在 ETH 耐药。在 15 例（33.3%）中鉴定出 inhA 启动子突变，其中 12/14（86%）分离株也对 ETH 耐药。在 21 例 katG 突变的分离株中，有 6 例（29%）对 ETH 耐药。没有分离株同时具有 katG 和 inhA 启动子突变。9 例（20%）分离株既没有 inhA 启动子突变也没有 katG 突变。在 15 例具有 inhA 启动子突变的分离株中，有 14 例（93%）显示低或中水平的 INH 耐药性。在 19 例 INH 敏感的分离株中，ETH 耐药见于 1/18（6%），且均未显示 inhA 或 katG 基因突变。
在该地理区域的儿童中，我们发现 INH 耐药的结核分枝杆菌分离株与 ETH 之间存在高水平的交叉和共同耐药性。
