2004至2021年臺灣引起流行性腦脊髓膜炎之腦膜炎雙球菌抗生素感受性分析

Antimicrobial Susceptibility of Neisseria meningitidis Causing Meningococcal Meningitis in Taiwan, 2004–2021

2017年7月北部某軍營發生流行性腦脊髓膜炎群聚事件，後發現分離自群聚個案血液或腦脊髓膜液的腦膜炎雙球菌對ciprofloxacin具有抗藥性，故對先前已接受ciprofloxacin預防性投藥之多位密切接觸者再次投予azithromycin。因此，本實驗室開始針對之後每年新通報的流行性腦脊髓膜炎確定個案的分離菌株批次進行抗生素感受性試驗，同時也溯及實驗室的庫存菌株。本研究報告即整理2004至2021年共118株腦膜炎雙球菌對9種抗生素的感受性試驗結果，以為未來防治的參考依據。這118株腦膜炎雙球菌對抗生素azithromycin、cefotaxime、ceftriaxone、rifampicin和meropenem具有100%敏感性(susceptible)；對chloramphenicol、ciprofloxacin、penicillin G和trimethoprim/sulfamethoxazole分別具有99.2%、88.1%、59.3%和5.9%敏感性。對ciprofloxacin不具敏感性的菌株最早於2006年分離出，2016年之後每年都出現；對penicillin G不具敏感性的菌株最早於2004年出現，除了2009年以外，每年都有分離出。關於腦膜炎雙球菌對ciprofloxacin和penicillin G可能的抗藥性機轉，定序結果顯示，對ciprofloxacin不具敏感性是由於DNA gyrase A譯碼基因gyrA上的T91I變異，而對penicillin G不具敏感性則是由於penicillin-binding protein 2 (PBP2)譯碼基因penA尾端具有與penicillin G不具敏感性相關的胺基酸變異。

An outbreak of meningococcal meningitis occurred in a military camp in northern Taiwan in July 2017. Later, Neisseria meningitidis isolates from blood and cerebrospinal fluid from confirmed cases were found to be resistant to ciprofloxacin, resulting in giving azithromycin to many close contacts who were previously given ciprofloxacin for antimicrobial chemoprophylaxis. Therefore, we began to test the antimicrobial susceptibility of all newly obtained N. meningitidis isolates causing meningococcal meningitis and strains in our collection. Among the 118 isolates collected from 2004 to 2021 against 9 antimicrobial agents, the susceptibility rates to azithromycin, cefotaxime, ceftriaxone, rifampicin, and meropenem were 100%, while the susceptibility rates to chloramphenicol, ciprofloxacin, penicillin G and trimethoprim/sulfamethoxazole were 99.2%, 88.1%, 59.3% and 5.9%, respectively. The first ciprofloxacin non-susceptible N. meningitidis isolate appeared in 2006 and has appeared every year since 2016. The first penicillin G non-susceptible N. meningitidis isolate appeared in 2004 and appeared every year except 2009. By DNA sequencing of related genes, the T91I mutation in the DNA gyrase A encoding gene gyrA and multiple mutations in the end portion of the penicillin-binding protein 2 (PBP2) encoding gene penA was likely responsible for antimicrobial resistance to ciprofloxacin and penicillin G, respectively.