Department of Medicine, University of Texas at Tyler School of Medicine, Tyler, TX, USA.
Mathematical Modeling and AI Department, Praedicare Inc., Dallas, TX, USA; Hollow Fiber System & Experimental Therapeutics Laboratories, Wet Lab Systems, Praedicare Inc., Dallas, TX, USA.
Tuberculosis (Edinb). 2024 Jul;147:102519. doi: 10.1016/j.tube.2024.102519. Epub 2024 May 13.
Drug susceptibility testing (DST) protocol of omadacycline against non-tuberculous mycobacteria has not yet been established. We developed a method to accurately determine MIC omadacycline MIC against Mycobacterium abscessus (Mab), Mycobacterium avium-complex (MAC), and Mycobacterium kansasii (Mkn).
First, we identified the oxyrase concentration not affecting Mab, MAC, and Mkn growth followed by omadacycline MIC experiments with and without oxyrase using reference and clinical strains.
Oxyrase 0.5 % (v/v) stabilized omadacycline in the culture medium. The median omadacycline MIC was 1 mg/L for Mab and 8 mg/L for Mkn. For MAC, the median omadacycline MIC was 2 mg/L for M. avium, 256 mg/L for M. intracellulare, and 4 mg/L for M. chimaera (p < 0.0001). Wilcoxon matched-pairs signed rank test revealed statistically lower MICs with oxyrase for all MAC subspecies (p < 0.0001), all Mab subspecies (p < 0.0001), and Mkn (p = 0.0002). The decrease in MICs with oxyrase was 17/18 of Mab, 14/19 of Mkn, 8/8 of M. avium, 4/5 M. chimera, but only 11/18 of M. intracellulare (p < 0.013).
Use of 0.5 % oxyrase could be a potential solution to reliable and reproducible omadacycline MIC of Mab. However, oxyrase demonstrated a variable effect in reducing MICs against MAC and Mkn.
目前尚未建立美满霉素（omadacycline）对非结核分枝杆菌的药敏试验（DST）方案。我们开发了一种方法，可准确测定脓肿分枝杆菌（Mab）、鸟分枝杆菌复合群（MAC）和堪萨斯分枝杆菌（Mkn）对美满霉素的 MIC 值。
首先，我们确定了不会影响 Mab、MAC 和 Mkn 生长的氧化酶浓度，然后使用参考菌株和临床分离株进行了有和无氧化酶的美满霉素 MIC 实验。
氧化酶 0.5%（v/v）稳定了培养基中的美满霉素。Mab 的美满霉素 MIC 中位数为 1mg/L，Mkn 为 8mg/L。对于 MAC，鸟分枝杆菌、胞内分枝杆菌和偶发分枝杆菌的美满霉素 MIC 中位数分别为 2mg/L、256mg/L 和 4mg/L（p<0.0001）。Wilcoxon 配对符号秩检验显示，所有 MAC 亚种（p<0.0001）、所有 Mab 亚种（p<0.0001）和 Mkn（p=0.0002）的 MIC 值均随氧化酶的使用而降低。氧化酶降低 MIC 值的情况为：18 株 Mab 中有 17 株、19 株 Mkn 中有 14 株、8 株鸟分枝杆菌中有 8 株、5 株偶发分枝杆菌中有 4 株，而胞内分枝杆菌只有 18 株中有 11 株（p<0.013）。
使用 0.5%氧化酶可能是可靠且重现性地测定 Mab 美满霉素 MIC 的一种潜在方法。然而，氧化酶在降低 MAC 和 Mkn 的 MIC 值方面表现出可变的效果。
