耐甲氧西林金黄色葡萄球菌临床分离株中磷霉素耐药性及基因突变的流行情况。
Prevalence of fosfomycin resistance and gene mutations in clinical isolates of methicillin-resistant Staphylococcus aureus.
机构信息
Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan.
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
出版信息
Antimicrob Resist Infect Control. 2020 Aug 17;9(1):135. doi: 10.1186/s13756-020-00790-x.
BACKGROUND
Fosfomycin exhibits excellent in vitro activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Increasing fosfomycin resistance among clinical MRSA isolates was reported previously, but little is known about the relative abundance of Fosfomycin resistance genes in MRSA isolates circulating in Taiwan.
METHODS
All MRSA isolates, collected in 2002 and 2012 by the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program, were used in this study. Susceptibility to various antimicrobial agents, including fosfomycin, was determined by broth microdilution. Genetic determinants of fosfomycin resistance, including fosB carriage and murA, glpT and uhpT mutations, were investigated using PCR and sequencing of amplicons. Staphylococcal protein A (spa) typing was also performed to determine the genetic relatedness of MRSA isolates.
RESULTS
A total of 969 MRSA strains, 495 in the year 2002 and 474 in the year 2012, were analyzed. The overall in vitro susceptibility was 8.2% to erythromycin, 18.0% to clindamycin, 29.0% to tetracycline, 44.6% to ciprofloxacin, 57.5% to trimethoprim/sulfamethoxazole, 86.9% to rifampicin, 92.9% to fosfomycin and 100% to linezolid and vancomycin. A significant increase in the fosfomycin resistance rate was observed from 3.4% in 2002 to 11.0% in 2012. Of 68 fosfomycin-resistant MRSA isolates, several genetic backgrounds probably contributing to fosfomycin resistance were identified. Twelve isolates harbored the fosB gene, and various mutations in murA, uhpT, and glpT genes were noted in 11, 59, and 66 isolates, respectively. The most prevalent gene mutations were found in the combination of uhpT and glpT genes (58 isolates). The vast majority of the fosfomycin-resistant MRSA isolates belonged to spa type t002.
CONCLUSIONS
An increased fosfomycin resistance rate of MRSA isolates was observed in our present study, mostly due to mutations in the glpT and uhpT genes. Clonal spread probably contributed to the increased fosfomycin resistance.
背景
磷霉素对包括耐甲氧西林金黄色葡萄球菌（MRSA）在内的多种耐药病原体具有出色的体外活性。先前已有报道称，临床分离的耐磷霉素 MRSA 株的耐药率不断增加，但有关台湾循环的 MRSA 分离株中磷霉素耐药基因的相对丰度知之甚少。
方法
本研究使用了 2002 年和 2012 年由台湾抗菌药物耐药监测计划（TSAR）收集的所有 MRSA 分离株。通过肉汤微量稀释法测定各种抗菌药物（包括磷霉素）的药敏性。采用 PCR 和扩增子测序检测磷霉素耐药的遗传决定因素，包括 fosB 携带和 murA、glpT 和 uhpT 突变。还进行了葡萄球菌蛋白 A（spa）分型以确定 MRSA 分离株的遗传相关性。
结果
共分析了 969 株 MRSA 菌株，其中 2002 年 495 株，2012 年 474 株。红霉素的总体体外敏感性为 8.2%，克林霉素为 18.0%，四环素为 29.0%，环丙沙星为 44.6%，复方磺胺甲噁唑为 57.5%，利福平为 86.9%，磷霉素为 92.9%，而利奈唑胺和万古霉素的敏感性为 100%。2002 年耐药率为 3.4%，2012 年耐药率为 11.0%，观察到磷霉素耐药率显著增加。在 68 株耐磷霉素的 MRSA 分离株中，鉴定出了几种可能导致磷霉素耐药的遗传背景。12 株分离株携带 fosB 基因，11 株分离株 murA 基因、59 株 uhpT 基因和 66 株 glpT 基因存在不同突变。最常见的基因突变发生在 uhpT 和 glpT 基因的组合中（58 株）。绝大多数耐磷霉素的 MRSA 分离株属于 spa 型 t002。
结论
本研究观察到耐磷霉素 MRSA 分离株的耐药率增加，主要是由于 glpT 和 uhpT 基因的突变。克隆传播可能导致磷霉素耐药性增加。
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