Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review.
Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review.
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DOI：
10.1371/journal.pone.0033275
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Rodwell TC
中科院分区：
文献类型：
--
作者：
Georghiou SB;Magana M;Garfein RS;Catanzaro DG;Catanzaro A;Rodwell TC
用于检测耐多药和广泛耐药结核病（M/XDR-TB）的快速分子诊断主要识别与耐药相关的结核分枝杆菌（Mtb）基因突变。然而，它们的准确性在很大程度上取决于特定突变与具有该突变的分离株的表型抗性之间的关联强度，这并不总是100%。虽然这种关系在一线抗结核药物利福平和异烟肼中得到了很好的确立和可靠，但对二线注射药物阿米卡星（AMK）、卡那霉素（KAN）和卷曲霉素（CAP）的研究和了解较少。我们对所有已发表的评估结核分枝杆菌突变与AMK、KAN、CAP耐药相关的研究进行了系统回顾，以表征突变的多样性和频率，并描述全球人群中特定突变与表型耐药之间的关联强度。我们的目的是确定这些突变作为检测AMK、KAN和CAP耐药性的诊断标记的潜在效用和可靠性。对来自四大洲和超过18个国家的1585株独特临床分离株的突变数据进行了审查。rrs、tlyA、eis启动子和gidB基因的突变与AMK、KAN和/或CAP抗性相关。rrs A1401G突变存在于大多数耐AMK、KAN和CAP的Mtb菌株中，但也存在于7%的CAP敏感菌株中。然而，仅发现1401突变的频率不足以检测到全球70-80%以上对AMK和CAP耐药的Mtb菌株，以及60%对KAN耐药的Mtb菌株。rrs、eis启动子、tlyA和gidB基因的其他突变似乎与耐药性有关，并可能提高未来诊断的敏感性和特异性。
Rapid molecular diagnostics for detecting multidrug-resistant and extensively drug-resistant tuberculosis (M/XDR-TB) primarily identify mutations in Mycobacterium tuberculosis (Mtb) genes associated with drug resistance. Their accuracy, however, is dependent largely on the strength of the association between a specific mutation and the phenotypic resistance of the isolate with that mutation, which is not always 100%. While this relationship is well established and reliable for first-line anti-TB drugs, rifampin and isoniazid, it is less well-studied and understood for second-line, injectable drugs, amikacin (AMK), kanamycin (KAN) and capreomycin (CAP). We conducted a systematic review of all published studies evaluating Mtb mutations associated with resistance to AMK, KAN, CAP in order to characterize the diversity and frequency of mutations as well as describe the strength of the association between specific mutations and phenotypic resistance in global populations. Our objective was to determine the potential utility and reliability of these mutations as diagnostic markers for detecting AMK, KAN and CAP resistance. Mutation data was reviewed for 1,585 unique clinical isolates from four continents and over 18 countries. Mutations in the rrs, tlyA, eis promoter and gidB genes were associated with AMK, KAN and/or CAP resistance. The rrs A1401G mutation was present in the majority of AMK, KAN and CAP resistant Mtb strains reviewed, but was also found in 7% of CAP susceptible strains. The 1401 mutation alone, however, was not found with sufficient frequency to detect more than 70–80% of global Mtb strains resistant to AMK and CAP, and 60% of strains resistant to KAN. Additional mutations in the rrs, eis promoter, tlyA and gidB genes appear to be associated with resistance and could improve sensitivity and specificity of future diagnostics.
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