台北某醫院醫療照護相關萬古黴素抗藥性屎腸球菌感染之分子流行病學分析

Molecular epidemiology of healthcare associated vancomycin-resistant Enterococcus faecium infections at a hospital in Taipei

Vancomycin-resistant Enterococcus（VRE）於1995年首次在台灣被發現。近年VRE醫療照護相關感染逐漸增多，但流行病學研究仍然相當缺乏，迄今仍未能研擬出有效防治對策。先前國內研究聚焦在VRE院內血流感染，尚未對所有類型VRE醫療照護相關感染進行完整分析。本研究擬對台北某醫院之萬古黴素抗藥性屎腸球菌（vancomycin-resistant Enterococcus faecium, VREfm）醫療照護相關感染病例進行分子流行病學分析。收集2014～2017年間醫療照護相關感染VREfm病人臨床資料及VREfm菌株。以脈衝式電泳（pulsed-field gel electrophoresis, PFGE）分析菌株同源性，同時以聚合酶鏈反應（polymerase chain reaction, PCR）方式檢測抗藥性基因van A、van B、van C及毒性基因esp（enterococcal surface protein gene）、acm（collagen adhesion gene）、hyl（hyaluronidase gene）等。總共收集54位病例，包括：泌尿道感染43例（79.6％），血流感染8例（14.8％）及其他部位感染3例（5.6％）。所有菌株的vancomycin最低抑菌濃度均大於32mg／L，對linezolid感受性則達100％。PFGE顯示部分菌株為同源，具完全相同PFGE型別。抗藥基因檢測顯示所有菌株皆具有van A（＋），另高比例菌株同時帶有毒性基因：88.9％ esp gene（＋）、13.0％ hyl gene（＋）、100％ acm gene（＋）。分子證據顯示VREfm醫療照護相關感染存在兩種模式：直接院內傳播及多源來源。後者可能與大量使用glycopeptide類抗生素造成的選擇壓力有關，但這需要進一步探究其相關性。

Vancomycin-resistant Enterococcus (VRE) was first detected in Taiwan in 1995, according to the data from the Taiwan Healthcare- associated infection and Antimicrobial resistance Surveillance, (THAS). Recently, healthcare-associated VRE infections have gradually increased; however, epidemiological research is still insufficient, resulting in a lack of effective prevention and control strategies so far. Previous domestic studies have focused only on nosocomial bloodstream infections, but investigation or analysis of nosocomial infections in VRE is insufficient. This study conducted a molecular epidemiological analysis of all cases with nosocomial vancomycin-resistant Enterococcus faecium (VREfm) infections at a hospital in Taipei between 2014 and 2017. Since 2014, we collected clinical data and strains from patients with VREfm infection and performed molecular typing using pulsedfield gel electrophoresis (PFGE) to investigate the role of the VREfm resistance gene in the collected strains. The VanA, VanB, VanC, enterococcal surface protein (Esp), collagen adhesion (Acm), and hyaluronidase (hyl) genes were detected by polymerase chain reaction testing. We collected 54 cases, including 43 (79.6%) patients with urinary tract infection, eight (14.8%) with bloodstream infection, and three (5.6%) with other infections. Resistance to vancomycin was > 32 mg/L in all strains but with 100% sensitive to linezolid. The PFGE results showed that some of the strains were 100% correlated. All strains showed 100% VanA positivity, 88.9% were Esp-positive, 13.0% exhibited hyl-positivity, and 100% were Acmpositive. Molecular evidence suggests two modes of healthcare-associated infection in VREfm: direct nosocomial transmission and multiple sources under selective pressure caused by antibiotics.