Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Division of Infectious Diseases, Department of Medicine, Geneva University Hospitals and Medical School, Geneva, Switzerland; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
J Glob Antimicrob Resist. 2023 Dec;35:137-142. doi: 10.1016/j.jgar.2023.09.003. Epub 2023 Sep 12.
Fosfomycin is a first-line treatment for uncomplicated urinary tract infections (UTIs) in several European countries, and it is increasingly becoming the treatment of choice globally. Resistance to fosfomycin in Escherichia coli can be exerted through several mechanisms, including the acquisition of fosfomycin-modifying enzymes, of which the FosA-type enzymes are the most common. This study analysed, both phenotypically and genotypically, an international collection of E. coli strains harbouring acquired fosA genes.
Thirty-one fosA-positive E. coli isolates were obtained from both clinical and environmental sources, from seven countries (Portugal (n = 12), Switzerland (n = 9), China (n = 3), France (n = 2), Nepal (n = 2), South Africa (n = 2), Kuwait (n = 1)). MICs were determined according to EUCAST guidelines. Whole genome sequencing (WGS) was performed on 23 isolates, and complete fosA plasmid sequences were determined for 12. Conjugation assays were performed on seven isolates.
All isolates exhibited high-level resistance to fosfomycin (64 to >256 mg/L). WGS of 23 isolates identified 17 sequence types (STs), and 16 harboured fosA3, four fosA4, two fosA8, and one fosA10. ESBLs, pAmpC, or carbapenemase genes were present in 15, four, and three isolates, respectively. The fosA plasmids of 12 isolates were determined and were diverse in size (∼67 kb to ∼235 kb), resistance gene carriage, and replicon types. Six fosA plasmids additionally carried ESBL or carbapenemase genes. Conjugation assays, performed on seven isolates harbouring diverse plasmids, identified that all were capable of being transmitted.
This study highlights the necessity of the surveillance and close monitoring of fosfomycin resistance in E. coli, essential to maintain the optimal use of this treatment option.
磷霉素是几个欧洲国家治疗单纯性尿路感染（UTIs）的一线药物，并且在全球范围内越来越成为治疗的首选。大肠杆菌对磷霉素的耐药性可以通过多种机制产生，包括获得磷霉素修饰酶，其中 FosA 型酶最为常见。本研究从表型和基因型两方面分析了携带获得性 fosA 基因的国际大肠杆菌菌株。
从来自七个国家（葡萄牙（n=12）、瑞士（n=9）、中国（n=3）、法国（n=2）、尼泊尔（n=2）、南非（n=2）、科威特（n=1））的临床和环境来源中获得了 31 株 fosA 阳性大肠杆菌分离株。根据 EUCAST 指南测定 MICs。对 23 株进行全基因组测序（WGS），并确定了 12 株 fosA 质粒的完整序列。对 7 株进行了接合试验。
所有分离株均对磷霉素表现出高水平耐药性（64 至 >256 mg/L）。对 23 株分离株的 WGS 鉴定出 17 种序列类型（STs），其中 16 株携带 fosA3，4 株携带 fosA4，2 株携带 fosA8，1 株携带 fosA10。15 株、4 株和 3 株分别携带 ESBLs、pAmpC 或碳青霉烯酶基因。12 株分离株的 fosA 质粒大小不同（约 67 kb 至约 235 kb），耐药基因携带情况和复制子类型也不同。6 株 fosA 质粒还携带 ESBL 或碳青霉烯酶基因。对携带不同质粒的 7 株分离株进行的接合试验表明，所有分离株都能够进行传递。
本研究强调了监测大肠杆菌中磷霉素耐药性的必要性，这对于维持这种治疗选择的最佳使用至关重要。
