Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, National Health and Family Planning Commission, Shanghai, China.
Public Health Research Institute and Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers University, Newark, NJ, USA.
Int J Antimicrob Agents. 2019 Jun;53(6):859-863. doi: 10.1016/j.ijantimicag.2019.02.017. Epub 2019 Mar 1.
The antimicrobial resistance crisis makes it critically important for laboratories to closely monitor trends and mechanisms of emerging antimicrobial resistance in clinical isolates. Bacteroides fragilis is an anaerobic pathogen that causes several serious infections and is increasingly resistant to antimicrobial agents. However, data from China regarding antimicrobial resistance in B. fragilis are limited. In this work, the mechanism underlying carbapenem resistance in 44 B. fragilis isolates collected from a Chinese hospital was investigated. Antimicrobial susceptibility testing for 13 antimicrobial agents was performed by the agar dilution method, and the contribution of efflux pumps to carbapenem resistance was analysed. Genetic relatedness of the isolates was determined by PFGE. Outer membrane porins were analysed in isolates with reduced carbapenem susceptibility. Potential carbapenemase-encoding genes were identified, and the location and environment of the cfiA gene was analysed. Among the 44 isolates, 18.2%, 29.5%, 22.7%, 100%, 100%, 29.5%, 15.9%, 81.8%, 88.6% and 47.7% were resistant to imipenem, meropenem, ertapenem, penicillin, ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam, clindamycin, tetracycline and moxifloxacin, respectively. None of the isolates were resistant to metronidazole, cefoxitin or chloramphenicol. A chromosomally located gene (cfiA) encoding a metallo-β-lactamase was identified in 16 isolates (36.4%). A conserved insertion sequence of IS1187 or IS613 was upstream of cfiA in eight isolates with high-level carbapenem resistance. The insertion sequences were associated with increased carbapenem resistance in B. fragilis by upregulating the expression of cfiA as shown by RT-qPCR. This is the first study to describe a mechanism of carbapenem resistance in B. fragilis in mainland China.
耐抗生素性危机使得实验室密切监测临床分离株中新出现的耐抗生素性的趋势和机制变得至关重要。脆弱拟杆菌是一种引起多种严重感染的厌氧病原体，并且对抗生素的耐药性日益增加。然而，关于中国脆弱拟杆菌的耐抗生素性数据有限。在这项工作中，研究了从中国一家医院收集的 44 株脆弱拟杆菌分离株中碳青霉烯类耐药的机制。采用琼脂稀释法对 13 种抗菌药物的药敏试验进行了检测，并分析了外排泵对碳青霉烯类耐药的贡献。通过 PFGE 确定了分离株的遗传相关性。分析了对碳青霉烯类药物敏感性降低的分离株的外膜孔蛋白。鉴定了潜在的碳青霉烯酶编码基因，并分析了 cfiA 基因的位置和环境。在 44 株分离株中，分别有 18.2%、29.5%、22.7%、100%、100%、29.5%、15.9%、81.8%、88.6%和 47.7%对亚胺培南、美罗培南、厄他培南、青霉素、氨苄西林、阿莫西林/克拉维酸、哌拉西林/他唑巴坦、克林霉素、四环素和莫西沙星耐药。没有分离株对甲硝唑、头孢西丁或氯霉素耐药。在 16 株分离株（36.4%）中鉴定出一个染色体定位的基因（cfiA），该基因编码一种金属β-内酰胺酶。在 8 株高水平碳青霉烯类耐药的分离株中，cfiA 的上游有一个保守的插入序列 IS1187 或 IS613。通过 RT-qPCR 显示，插入序列通过上调 cfiA 的表达与脆弱拟杆菌的碳青霉烯类耐药性增加有关。这是首次在中国描述脆弱拟杆菌碳青霉烯类耐药的机制。
