Torrea Gabriela, Coeck Nele, Desmaretz Christel, Van De Parre Tim, Van Poucke Tijs, Lounis Nacer, de Jong Bouke C, Rigouts Leen
Department of Biomedical Sciences, Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium
Department of Biomedical Sciences, Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
J Antimicrob Chemother. 2015 Aug;70(8):2300-5. doi: 10.1093/jac/dkv117. Epub 2015 May 14.
The objective of this study was to evaluate the performance of the BACTEC MGIT960 system to test the susceptibility to bedaquiline for Mycobacterium tuberculosis complex.
We determined the quality control (QC) range of bedaquiline using the M. tuberculosis H37Rv reference strain and the epidemiological cut-off (ECOFF) in MGIT960 and on Middlebrook 7H11 agar (M7H11) using 47 strains from bedaquiline treatment-naive patients. The accuracy of MGIT960 was evaluated versus M7H11 using 74 'probably susceptible to bedaquiline' and 18 'probably resistant to bedaquiline' strains. Repeatability and reproducibility of MGIT960 were assessed using five strains showing different resistance levels.
The QC range for the H37Rv strain was between 0.125 and 0.50 mg/L. The WT MIC distribution ranged from ≤0.03 to 1.00 mg/L in MGIT960 and from ≤0.008 to 0.25 mg/L on M7H11 with suggested ECOFFs of 1.00 and 0.25 mg/L, respectively. Applying these ECOFFs, the probably susceptible and probably resistant strains were distinguishable by both methods, albeit with only a 2-fold increased MIC for one of the resistant strains compared with the ECOFF. Intermethod agreement to classify the isolates was excellent (100%). All replicates in the repeatability and reproducibility experiments fell within the normal range.
The MGIT960 system proved to be highly stable, reproducible and accurate relative to the M7H11 agar method for determining the bedaquiline MIC. The small margin between the suggested ECOFF and the lowest MIC for the mutant strains risks making both methods prone to discordant results. Further validation in clinical settings linked to treatment outcome data is needed.
本研究的目的是评估BACTEC MGIT960系统检测结核分枝杆菌复合群对贝达喹啉敏感性的性能。
我们使用结核分枝杆菌H37Rv参考菌株确定了贝达喹啉的质量控制（QC）范围，并使用来自未接受过贝达喹啉治疗患者的47株菌株，在MGIT960和Middlebrook 7H11琼脂（M7H11）上确定了流行病学截断值（ECOFF）。使用74株“可能对贝达喹啉敏感”和18株“可能对贝达喹啉耐药”的菌株，评估MGIT960相对于M7H11的准确性。使用五株显示不同耐药水平的菌株评估MGIT960的重复性和再现性。
H37Rv菌株的QC范围在0.125至0.50 mg/L之间。在MGIT960中，野生型最低抑菌浓度（MIC）分布范围为≤0.03至1.00 mg/L，在M7H11上为≤0.008至0.25 mg/L，建议的ECOFF分别为1.00和0.25 mg/L。应用这些ECOFF，两种方法均可区分可能敏感和可能耐药的菌株，尽管其中一株耐药菌株的MIC仅比ECOFF增加了2倍。两种方法对分离株分类的一致性极佳（100%）。重复性和再现性实验中的所有重复结果均在正常范围内。
相对于M7H11琼脂法，MGIT960系统在确定贝达喹啉MIC方面被证明具有高度稳定性、可重复性和准确性。建议的ECOFF与突变菌株最低MIC之间的差距较小，这可能使两种方法都容易出现不一致的结果。需要在与治疗结果数据相关的临床环境中进行进一步验证。
