Infections caused by nontuberculous mycobacteria (NTM) are increasing globally. Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex are the most frequently encountered NTM, and oral treatment options are extremely limited for these pathogens, especially for the M. abscessus complex. In this study, the in vitro potency of omadacycline, a new tetracycline derivative, was tested against 111 isolates of NTM. MIC testing was performed as recommended by the Clinical and Laboratory Standards Institute against 70 isolates of rapidly growing mycobacteria (RGM), of which >90% were tetracycline resistant. These included M. abscessus subsp. abscessus (20 isolates), M. abscessus subsp. massiliense (3), Mycobacterium chelonae (15 isolates), Mycobacterium immunogenum (7 isolates), the Mycobacterium fortuitum group, including six doxycycline-resistant isolates (12 isolates), and the Mycobacterium mucogenicum group, including four doxycycline-resistant isolates (10 isolates). Forty-one isolates of slowly growing mycobacteria (SGM), including 16 isolates of MAC, were also tested. Omadacycline was active against all RGM species, with MIC₅₀ ranges of 0.004 to 0.25 and 0.06 to 1 μg/ml for 80% and 100% inhibition, respectively. For M. abscessus subsp. abscessus, MIC₅₀s were 0.06 and 0.12 μg/ml with 80% and 100% inhibition, respectively. There was considerable trailing of the omadacycline endpoint with the RGM. MICs of tigecycline exhibited no trailing and were generally within 1 to 2 dilutions of the 100% inhibition omadacycline MICs. While there was no trailing observed in SGM, omadacycline MICs were higher (MIC range, 8 to >16 μg/ml; n = 41), as previously noted with tigecycline. This study supports further research of omadacycline, including clinical trials, for the treatment of RGM infections, especially M. abscessus.

中文翻译：

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奥马达环素对非结核分枝杆菌的体外药敏试验

由非结核分枝杆菌 (NTM) 引起的感染在全球范围内正在增加。鸟分枝杆菌复合体 (MAC) 和脓肿分枝杆菌复合体是最常见的 NTM，对于这些病原体，尤其是脓肿分枝杆菌复合体，口服治疗选择极其有限。在这项研究中，测试了omadacycline（一种新的四环素衍生物）对 111 种 NTM 分离株的体外效力。按照临床和实验室标准协会的建议，对 70 株快速生长的分枝杆菌 (RGM) 分离株进行了 MIC 测试，其中 >90% 对四环素耐药。这些包括M. abscessus subsp。脓肿（20 株），M. abscessus subsp. massiliense (3)、龟分枝杆菌(15株)、免疫原分枝杆菌(7株)、偶发分枝杆菌组，包括6株强力霉素耐药株(12株)和粘液分枝杆菌组，包括4株强力霉素耐药株(10株) ）。还测试了 41 株缓慢生长的分枝杆菌 (SGM)，包括 16 株 MAC。奥马达环素对所有 RGM 物种均有活性，MIC ₅₀范围分别为 0.004 至 0.25 和 0.06 至 1 μg/ml，抑制率分别为 80% 和 100%。对于M. abscessus subsp。脓肿,MIC ₅₀s 分别为 0.06 和 0.12 μg/ml，抑制率分别为 80% 和 100%。RGM 的 omadacycline 终点有相当大的拖尾。替加环素的 MIC 没有出现拖尾现象，通常在 100% 抑制性 omadacycline MIC 的 1 到 2 倍稀释范围内。虽然在 SGM 中没有观察到拖尾现象，但 omadacycline MICs 更高（MIC 范围，8 到 >16 μg/ml；n = 41），正如之前用替加环素所指出的那样。本研究支持 omadacycline 的进一步研究，包括临床试验，用于治疗 RGM 感染，尤其是脓肿分枝杆菌。