結核分枝桿菌對立汎黴素的抗藥機轉及WHO認可的快速檢驗立汎黴素抗藥株之方法

The Molecular Mechanism and WHO-endorsed Diagnosis of Rifampicin Resistance in Mycobacterium tuberculosis

立汎黴素(rifampicin)是治療結核病的第一線藥物之一，細菌對立汎黴素產生抗藥性最常見的原因是細菌rpoB基因產生突變，導致其編碼(encode)產生核糖核酸聚合酶(RNA polymerase)的β次單元(β–subunit)也發生突變。而這些突變大多集中在一段長度為81-bp DNA區域，稱為rifampicin resistance-determining region(簡稱RRDR)，但也有報導發現有些抗立汎黴素的抗藥菌株則是在RRDR以外的區域及輸出幫浦(efflux pumps)發生突變所造成。本篇綜論介紹rpoB基因的點突變與立汎黴素抗藥性機轉之關聯性及六種世界衛生組織已認可的快速檢驗抗立汎黴素菌株的方法：microscopic observation of drug susceptibility (MODS), nitrate reductase assay (NRA), colorimetricredox indicator (CRI), INNO-LiPA Rif. TB, Xpert® MTB/RIF test以及GenoType®MTBDRplus (包括MTBDR) assay。

Rifampicin is one of first-line drugs used in the treatment of tuberculosis (TB). Increasing rifampicin resistance hampers effective TB treatment. Resistance to rifampicin is commonly caused by mutation in the rpoB gene encoding the β–subunit of RNA polymerase. Mutations of 81-bp rifampicin resistance-determining region (RRDR) of the rpoB gene associate with most of rifampicin resistance in clinical strains. However, mutations outside RRDR and efflux pumps have been reported to be involved in rifampicin resistance. Rapid test for rifampicin resistance is important for improving patient care and decreasing TB transmission. World health organization (WHO) has endorsed rapid phenotypic tests, microscopic observation of drug susceptibility (MODS), nitrate reductase assay (NRA) and colorimetric redox indicator (CRI), and molecular tests, INNO-LiPA Rif. TB, Xpert® MTB/RIF test, GenoType® MTBDR assay and GenoType® MTBDRplus assay, for rifampicin resistance and recommended the use of rapid tests in high risk multidrug-resistant TB (MDR-TB) settings. This review article focuses on the various site mutation in rpoB associated with mycobacterial rifampicin resistance and summarizes the performance of these WHO-endorsed rapid tests for rifampicin resistance.