2010至2024年臺灣對macrolide具有抗藥性的百日咳桿菌的分析

Macrolide-resistant Bordetella pertussis strains in Taiwan, 2010–2024

2020年，透過疾病管制署與日本的合作計畫，首次發現臺灣2011年和2012年的百日咳分離菌株中各有1株對macrolide類抗生素具有抗藥性，因此疾病管制署檢驗及疫苗研製中心開始經常性監測國內百日咳菌株抗藥性。本研究分析2010-2024年間71株流行病學上不相關的百日咳分離菌株的抗藥性監測結果。對於macrolide類抗生素，包含azithromycin、clarithromycin與erythromycin，具有抗藥性的菌株有10株，最低抑菌濃度皆大於256mg/mL，是macrolide-resistant Bordetella pertussis（MRBP）菌株；對於抗生素trimethoprim/sulfamethoxazole則皆具有敏感性。MRBP菌株最早出現於2011年，2012年和2015年各有一株，2020年兩株，2022年1株，而2024年則有4株。10株MRBP菌株對macrolide類抗生素的抗藥性機轉，皆因在23S rRNA基因上有A2047G的突變位點。進一步分析10株MRBP菌株，結果顯示很可能皆源自中國，包括：分離於2011–2022年間的6株，重要抗原基因型別為ptxA1/prn1/fim3-1/ptxP1；分離於2024年的4株為ptxA1/prn2/fim3-1/ptxP3；MLVA型別（multilocus variable-number tandem-repeat analysis）包含MT195、MT28、MT104和MT290；pulsed-field gel electrophoresis（PFGE）DNA指紋圖譜將菌株分為3群，其中2024年有3株菌株具有相同的指紋圖譜，包含中國境外移入患者的菌株；2011–2012年的2株MRBP菌株的全基因體定序結果與中國的MRBP菌株相近。本分析結果可作為未來治療與預防性投藥的參考依據，建議持續監測百日咳菌株的抗藥性。

In 2020, through the collaborative study on Bordetella pertussis between the Taiwan Centers for Disease Control and the National Institute for Infectious Diseases in Japan, the first two macrolide-resistant Bordetella pertussis (MRBP) strains were identified in Taiwan in 2011 and 2012. Therefore, we began to monitor the antimicrobial susceptibility of all newly obtained B. pertussis strains in Taiwan. Here, we report the analysis of 71 B. pertussis strains collected during 2010–2024 for resistance against trimethoprimsulfamethoxazole and macrolides, including azithromycin, clarithromycin, and erythromycin. All strains were sensitive to trimethoprim-sulfamethoxazole. Ten strains were macrolide-resistant, with minimum inhibitory concentration (MIC) > 256 g/mL against all three macrolides. The first MRBP strain was isolated in 2011, followed by one strain in 2012, one in 2015, two in 2020, one in 2022, and four in 2024. All 10 MRBP strains had an A2047G mutation in the 23S rRNA gene, causing the macrolide-resistant phenotype. Further characterization of these 10 MRBP strains indicated that these strains may have originated from China. The MRBP strains from 2011 to 2022 had the ptxA1/prn1/fim3-1/ptxP1 genotype, while MRBP stains from 2024 had the ptxA1/prn2/fim3-1/ptxP3 genotype. The multilocus variable-number tandem repeat analysis (MLVA) types were MT195, MT28, MT104 and MT290. The pulsed-field gel electrophoresis (PFGE) DNA fingerprinting separated the 10 MRBP strains into 3 groups. Three strains isolated in 2024 had identical fingerprints, which included one strain imported from China. Also, whole genome sequencing for the first 2 MRBP strains indicated that they were closer to MRBP strains from China. Our results provide guidance for the treatment and antibiotic prophylaxis of pertussis, and indicate that continued monitoring of antimicrobial susceptibility of B. pertussis strains is essential.