异烟肼耐药相关突变对单耐药结核分枝杆菌临床表现的影响。
Impact of isoniazid resistance-conferring mutations on the clinical presentation of isoniazid monoresistant tuberculosis.
机构信息
Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America.
出版信息
PLoS One. 2012;7(5):e37956. doi: 10.1371/journal.pone.0037956. Epub 2012 May 23.
BACKGROUND
Specific isoniazid (INH) resistance conferring mutations have been shown to impact the likelihood of tuberculosis (TB) transmission. However, their role in the clinical presentation and outcomes of TB has not been evaluated.
METHODS
We included all cases of culture-confirmed, INH monoresistant tuberculosis reported to the San Francisco Department of Public Health Tuberculosis Control Section from October 1992 through October 2005. For cases with stored culture isolates, we used polymerase chain reaction (PCR) testing and gene sequencing to identify INH resistance-conferring mutations, and compared genotypic and phenotypic characteristics.
RESULTS
Among 101 consecutive cases of INH monoresistant TB in San Francisco 19 (19%) had isolates with a katG mutation other than S315T; 38 (38%) had isolates with the katG S315T mutation, 29 (29%) had isolates with a inhA-15;c-t promoter mutation, and 15 (15%) had isolates with other mutations. The katG S315T mutation was independently associated with high-level INH resistance (risk ratio [RR] 1.56, 95% confidence interval [CI] 1.07-2.27), and the inhA-15;c-t promoter mutation was inversely associated with high-level INH resistance (RR 0.43, 95% CI 0.21-0.89). However, specific INH resistance-conferring mutations were not associated with the clinical severity or outcomes of INH monoresistant TB cases.
CONCLUSION
These data suggest that INH resistance-conferring mutations do not impact the clinical presentation of TB.
背景
已证实特定的异烟肼（INH）耐药相关突变会影响结核病（TB）的传播概率。然而，它们在 TB 的临床表现和结局中的作用尚未得到评估。
方法
我们纳入了 1992 年 10 月至 2005 年 10 月间旧金山公共卫生部结核病控制科报告的所有培养确诊的 INH 单耐药性结核病病例。对于有存储培养分离株的病例，我们使用聚合酶链反应（PCR）检测和基因测序来鉴定 INH 耐药相关突变，并比较了基因型和表型特征。
结果
在旧金山的 101 例 INH 单耐药性结核病连续病例中，有 19 例（19%）的分离株具有除 S315T 以外的 katG 突变；38 例（38%）的分离株具有 katG S315T 突变，29 例（29%）的分离株具有 inhA-15；c-t 启动子突变，15 例（15%）的分离株具有其他突变。katG S315T 突变与高水平 INH 耐药独立相关（风险比 [RR] 1.56，95%置信区间 [CI] 1.07-2.27），inhA-15；c-t 启动子突变与高水平 INH 耐药呈负相关（RR 0.43，95% CI 0.21-0.89）。然而，特定的 INH 耐药相关突变与 INH 单耐药性结核病病例的临床严重程度或结局无关。
结论
这些数据表明 INH 耐药相关突变不会影响 TB 的临床表现。
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