Ka Lip Chew, Go Joelle, Binte Abu Bakar Nur Aisyah, Octavia Sophie, Pin Lin Raymond Tzer, Teo Jeanette W P
Department of Laboratory Medicine, National University Hospital, Singapore, Singapore.
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
Microbiol Spectr. 2025 Feb 4;13(2):e0160024. doi: 10.1128/spectrum.01600-24. Epub 2025 Jan 10.
The complex (MAC) is a common causative agent causing nontuberculous mycobacterial (NTM) pulmonary disease worldwide. Whole-genome sequencing was performed on a total of 203 retrospective MAC isolates from respiratory specimens. Phylogenomic analysis identified eight subspecies and species. subspecies (MAH) was the overwhelmingly dominant species (148/203, 72.9%). The other seven identified species were subsp. (18/203, 8.9%), subsp. (10/203, 4.9%), (11/203, 5.4%), (6/203, 3%), (5/203, 2.5%), (3/203, 1.5%), and subspecies (2/203, 1%). Significant genetic clustering was observed among MAH isolates. Notably, a large cluster (<12 SNPs) of 76 MAH isolates bearing the same sequence type was observed. The presence of closely related isolates within hospital settings raises concerns about transmission routes with environmental sources potentially playing a significant role. Based on susceptibility breakpoints that are available for clarithromycin, amikacin, linezolid, and moxifloxacin, low rates of clarithromycin (0.5%, 1/203) and amikacin (1.5%, 3/203) phenotypic resistance were observed. While linezolid and moxifloxacin resistance were 25.6% (52/2030) and 46.3% (94/203), respectively. Drug resistance-associated loci were searched for mutations linked to phenotypic drug resistance. Of the entire cohort, only one isolate was found to have a A2059G 23S rRNA () gene mutation responsible for macrolide resistance.
complex (MAC) infections are increasingly challenging to manage due to their complex species diversity and varied resistance patterns. This study underscores the genetic diversity within MAC, identifying at least eight species and subspecies among 203 clinical isolates, with subsp. (MAH) being most prevalent at 72.9%. Notably, genetic clustering was observed within MAH and subsp. , suggesting potential transmission routes within healthcare settings. Clarithromycin and amikacin resistance was found to be uncommon, aligning with the rarity of resistance-associated genetic mutations. These findings emphasize the need for enhanced infection control measures and routine susceptibility testing to tailor antibiotic therapies effectively.
鸟分枝杆菌复合体（MAC）是全球非结核分枝杆菌（NTM）肺病的常见病原体。对来自呼吸道标本的总共203株回顾性MAC分离株进行了全基因组测序。系统基因组分析鉴定出8个亚种和种。脓肿分枝杆菌亚种（MAH）是绝对占主导地位的种（148/203，72.9%）。鉴定出的其他7个种分别是堪萨斯分枝杆菌亚种（18/203，8.9%）、胞内分枝杆菌亚种（10/203，4.9%）、龟分枝杆菌（11/203，5.4%）、蟾分枝杆菌（6/203，3%）、戈登分枝杆菌（5/203，2.5%）、玛尔摩分枝杆菌（3/203，1.5%）和溃疡分枝杆菌亚种（2/203，1%）。在MAH分离株中观察到显著的基因聚类。值得注意的是，观察到76株MAH分离株的一个大聚类（<12个单核苷酸多态性）具有相同的序列类型。医院环境中存在密切相关的分离株引发了对传播途径的担忧，环境源可能起着重要作用。根据克拉霉素、阿米卡星、利奈唑胺和莫西沙星可用的药敏断点，观察到克拉霉素（0.5%，1/203）和阿米卡星（1.5%，3/203）表型耐药率较低。而利奈唑胺和莫西沙星耐药率分别为25.6%（52/203）和46.3%（94/203）。搜索与耐药相关的基因座，寻找与表型耐药相关的突变。在整个队列中，仅发现一株分离株具有导致大环内酯耐药的A2059G 23S rRNA（）基因突变。
鸟分枝杆菌复合体（MAC）感染因其复杂的物种多样性和多样的耐药模式，管理起来越来越具有挑战性。本研究强调了MAC内的遗传多样性，并在203株临床分离株中鉴定出至少8个种和亚种，其中脓肿分枝杆菌亚种（MAH）最为常见，占72.9%。值得注意的是，在MAH和堪萨斯分枝杆菌亚种内观察到基因聚类，提示医疗机构内可能存在传播途径。发现克拉霉素和阿米卡星耐药并不常见，这与耐药相关基因突变的罕见性相符。这些发现强调了加强感染控制措施和进行常规药敏试验以有效调整抗生素治疗的必要性。
