Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Antimicrob Agents Chemother. 2018 Mar 27;62(4). doi: 10.1128/AAC.01788-17. Print 2018 Apr.
Very few studies have examined drug susceptibility of , and they involve a limited number of strains. The purpose of this study was to determine drug susceptibility profiles of isolates representing a spectrum of species genotypes (subtypes) with two different methodologies, i.e., broth microdilution and Etest assays. To confirm drug resistance, drug target genes were sequenced. A collection of 85 isolates, including representatives of eight different subtypes (I to VI, I/II, and IIB) from eight countries, was used. Drug susceptibility against 13 and 8 antimycobacterial agents was tested by using broth microdilution and Etest, respectively. For drug-resistant or high-MIC isolates, eight structural genes (, , , , , , , and ) and one regulatory region () were PCR amplified and sequenced in the search for resistance-associated mutations. All isolates tested were susceptible to rifampin (RIF), amikacin (AMK), co-trimoxazole (SXT), rifabutin (RFB), moxifloxacin (MXF), and linezolid (LZD) according to the microdilution method. Resistance to ethambutol (EMB), ciprofloxacin (CIP), and clarithromycin (CLR) was found in 83 (97.7%), 17 (20%), and 1 (1.2%) isolate, respectively. The calculated concordance between the Etest and dilution method was 22.6% for AMK, 4.8% for streptomycin (STR), 3.2% for CLR, and 1.6% for RIF. For EMB, INH, and SXT, not even a single MIC value determined by one method equaled that by the second method. The only mutations disclosed were A2266C transversion at the gene (CLR-resistant strain) and A128G transition at the gene (strain with STR MIC of >64 mg/liter). In conclusion, eight drugs, including RIF, CLR, AMK, SXT, RFB, MXF, LZD, and ethionamide (ETO), showed high activity against isolates. Discrepancies of the results between the reference microdilution method and Etest preclude the use of the latter for drug susceptibility determination in Drug resistance in may have different genetic determinants than resistance to the same drugs in .
很少有研究检测过 对药物的敏感性,并且这些研究涉及的菌株数量有限。本研究的目的是使用两种不同的方法,即肉汤微量稀释法和 Etest 测定法,来确定代表一系列种基因型(亚型)的 分离株的药物敏感性谱。为了确认药物耐药性,对药物靶基因进行了测序。使用来自八个国家的 85 株分离株,包括 8 种不同亚型(I 至 VI、I/II 和 IIB)的代表,进行了对 13 种和 8 种抗分枝杆菌药物的敏感性测试,分别使用肉汤微量稀释法和 Etest 进行。对于耐药或高 MIC 分离株,使用 PCR 扩增并对八个结构基因(、、、、、、和)和一个调节区()进行测序,以寻找耐药相关的突变。根据微量稀释法,所有分离株均对利福平(RIF)、阿米卡星(AMK)、复方磺胺甲噁唑(SXT)、利福布汀(RFB)、莫西沙星(MXF)和利奈唑胺(LZD)敏感。根据微量稀释法,分别有 83(97.7%)、17(20%)和 1(1.2%)株分离株对乙胺丁醇(EMB)、环丙沙星(CIP)和克拉霉素(CLR)耐药。Etest 和稀释法之间的一致性计算结果为 AMK 为 22.6%,链霉素(STR)为 4.8%,CLR 为 3.2%,RIF 为 1.6%。对于 EMB、INH 和 SXT,甚至没有一个方法确定的 MIC 值与另一个方法相同。唯一揭示的突变是 基因的 A2266C 颠换(CLR 耐药株)和 基因的 A128G 转换(STR MIC>64mg/L 株)。总之,包括 RIF、CLR、AMK、SXT、RFB、MXF、LZD 和乙硫异烟胺(ETO)在内的八种药物对 分离株具有高活性。参考微量稀释法和 Etest 之间的结果差异排除了后者在 中用于药物敏感性测定的可能性。 可能具有与相同药物耐药性不同的遗传决定因素。