Department of problems of laboratory diagnostics of tuberculosis and pathomorphology, Scientific and Clinical Antituberculosis Center of Moscow Government Health Department, Moscow, Russian Federation.
City consultation diagnostic center, Scientific and Clinical Antituberculosis Center of Moscow Government Health Department, Moscow, Russian Federation.
PLoS One. 2018 Sep 17;13(9):e0203108. doi: 10.1371/journal.pone.0203108. eCollection 2018.
The objective of the research was to assess the susceptibility of the slowly growing nontuberculous mycobacteria strains to the antimicrobial drugs used for mycobaterioses treatment using SLOMYCO test system.
We assessed 363 NTM strains: 177 MAC (161 M. avium, 16 M. intracellulare), 112 M. kansasii and 74 M. xenopi collected from the respiratory material of the patients were under the treatment or under diagnostic procedures at our Center, affiliates and the diagnostic department in 2010-2016. Drug sucseptibility for NTM was tested using the Sensititre SLOWMYCO system (TREK DIAGNOSTIC Systems Ltd., UK). MICs were established by microdilutions in Mueller-Hinton broth on polystyrene 96-well plates. The statistical analysis was done using the StatGraphics Plus 5.0 software. The data were compared pairwise using Pearson χ2 test with Yates correction. 95% confidence interval (CI) were calculated. Statistically significant differences were considered for p <0.05. Log-rank test and Kaplan-Meier curves were used to assess the concentration-dependent surveillance probability.
The statistically significant differences were revealed in sensitivity/resistance isolates of M. avium and M. intracellulare: M. avium strains were resistant to higher concentrations of amikacin, clarithromycin, linezolid and streptomycin (p <0.01); M. intracellulare strains were resistant to higher concentrations of ethionamide (p <0.05). The isolates of M. avium were significantly more resistant than M. kansasii to amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin, rifabutin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, ethionamide (visible growth of M. avium were inhibited by higher drug concentrations, p <0.01). The isolates of M. avium showed significantly higher resistance than M. xenopi to amikacin, doxycycline, isoniazid, clarithromycin, linezolid, moxifloxacin, rifampicin, streptomycin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (visible growth of M. avium were inhibited by higher drug concentrations, p <0.01). Statistically significant differences in the dynamics of the response to the antibacterial effects of isoniazid, linezolid, moxifloxacin, rifampicin, trimethoprim/sulfamethoxazole, ethambutol, and ethionamide were found for M. intracellulare and M. xenopi (complete inhibition of the visible growth of M. intracellulare required higher drugs concentrations, p <0, 05). Comparison of the Kaplan-Meyer curves revealed statistically significant differences in survialence probability of M. kansasii and M. xenopi for amikacin, doxycycline, rifampicin, trimethoprim/sulfamethoxazole, ciprofloxacin, ethambutol, and ethionamide (a higher number of isolates of M. xenopi were inhibited by low drugs concentrations, p <0.05).
Our data show that M. avium and M. intracellulare were more resistant to the majority of the studied drugs than M. kansasii and M. xenopi.
本研究旨在使用 SLOMYCO 测试系统评估缓慢生长的非结核分枝杆菌菌株对用于治疗分枝杆菌病的抗菌药物的敏感性。
我们评估了 363 株 NTM 菌株:177 株 MAC(161 株鸟分枝杆菌、16 株胞内分枝杆菌)、112 株堪萨斯分枝杆菌和 74 株 Xenopi,这些菌株均来自我们中心、分支机构和诊断部门在 2010-2016 年间治疗或诊断过程中收集的呼吸道标本。使用 Sensititre SLOWMYCO 系统(TREK DIAGNOSTIC Systems Ltd.,英国)测试 NTM 的药物敏感性。通过在聚苯乙烯 96 孔板上的 Mueller-Hinton 肉汤中进行微量稀释来确定 MIC。使用 Statgraphics Plus 5.0 软件进行统计分析。使用 Pearson χ2 检验(带有 Yates 校正)进行两两比较。计算 95%置信区间(CI)。p <0.05 被认为具有统计学显著差异。使用对数秩检验和 Kaplan-Meier 曲线评估浓度依赖性监测概率。
在鸟分枝杆菌和胞内分枝杆菌的敏感/耐药分离株中发现了统计学显著差异:鸟分枝杆菌株对阿米卡星、克拉霉素、利奈唑胺和链霉素的敏感性较低(p <0.01);胞内分枝杆菌株对乙胺丁醇的敏感性较低(p <0.05)。鸟分枝杆菌分离株对阿米卡星、强力霉素、异烟肼、克拉霉素、利奈唑胺、莫西沙星、利福布汀、利福平、链霉素、甲氧苄啶/磺胺甲恶唑、环丙沙星、乙胺丁醇和乙硫异烟胺的耐药性明显高于堪萨斯分枝杆菌(可见鸟分枝杆菌生长的药物浓度较高,p <0.01)。鸟分枝杆菌分离株对阿米卡星、强力霉素、异烟肼、克拉霉素、利奈唑胺、莫西沙星、利福平、链霉素、甲氧苄啶/磺胺甲恶唑、环丙沙星、乙胺丁醇和乙硫异烟胺的耐药性明显高于 Xenopi(可见鸟分枝杆菌生长的药物浓度较高,p <0.01)。对异烟肼、利奈唑胺、莫西沙星、利福平、甲氧苄啶/磺胺甲恶唑、乙胺丁醇和乙硫异烟胺的抗菌作用的反应动力学,在胞内分枝杆菌和 Xenopi 中存在统计学显著差异(可见胞内分枝杆菌的生长完全被抑制所需的药物浓度较高,p <0.05)。对堪萨斯分枝杆菌和 Xenopi 的阿米卡星、强力霉素、利福平、甲氧苄啶/磺胺甲恶唑、环丙沙星、乙胺丁醇和乙硫异烟胺的生存概率的 Kaplan-Meier 曲线比较显示出统计学显著差异(可见 Xenopi 的分离株被低浓度药物抑制的数量较多,p <0.05)。
我们的数据表明,鸟分枝杆菌和胞内分枝杆菌对大多数研究药物的耐药性明显高于堪萨斯分枝杆菌和 Xenopi。