廣泛抗藥性鮑氏不動桿菌抗藥性機轉及院內感染危險因子

Abstract

Acinetobacter baumannii（鮑氏不動桿菌，簡稱 A. baumannii）抗藥性問題近年來在醫療照護相關感染防治上日益受到重視，依據Taiwan Nosocomial Infections Surveillance System(TNIS)統計資料顯示：醫學中心及區域醫院加護病房 carbapenem-resistant A. Baumannii 的比率從 2003 年不到 20%，逐年上升至 2010年第三季已達約 70%，本研究探討在某醫學中心自 2008 年到 2010年 (25個月) 期間，extensively drug-resisitant A. baumannii (XDRAB) 院內感染菌株的 Integron 抗藥性基因及 OXA(oxacillinases) typing 的分型情形，以了解其水解酵素種類及抗藥性機制，並以脈衝電泳分型（Pulsed-Field Gel Electrophoresis Analysis, PFGE）釐清院內 XDRAB 菌株間相關性，配合病例對照研究 (病例組：對照組=1︰4 配對) 探討 XDRAB 院內感染的危險因子。研究結果顯示 25 株 XDRAB 中有 23 株所帶的 Integron 均為 class I，且其所帶的 Gene cassette 大小皆為 2300 kb。所有 XDRAB 菌株都不帶有 class II Integron。在 OXA typing 的分型部份，可以看到大部分都帶有 OXA 23 (21株，84%) 和 OXA 51 (25株，100%)。所有 XDRAB 菌株經過 PFGE 分型鑑定後，以相似度為 80% 做切點可以分成14大類，並無單一顯著分子型別，在研究期間發生 XDRAB 院內群聚感染可能性相對較低，但是考量環境因素仍無法完全排除。病例對照研究結果為：在單變項分析中，長期臥床、血液透析、氣切、使用glycopeptide、使用imipenem or meropenem、使用 anti-Pseudomonal penicillins、使用第四代 cephalosporins 等均為發生 XDRAB 院內感染之顯著危險因子；以多變項 conditional logistic regression 調整干擾作用後，長期臥床（adjusted odds ratio 5.2, 95%CI: 1.1–24.4）及使用 imipenem、meropenem、anti- Pseudomonal penicillins、或第四代 cephalosporins（adjusted odds ratio 4.3, 95%CI: 1.4–12.7）兩變項均為發生 XDRAB 院內感染之獨立危險因子。本研究結論為：適當管制後線抗革蘭氏陰性菌抗生素的使用，為防治 XDRAB 院內感染不可或缺的一環。

The emergence of drug-resistant Acinetobacter baumannii (A. baumannii) is now a serious problem in healthcare-associated infections (HAIs) control. Data from Taiwan TINS showed that, while the percentage of carbapenem-resistant A. baumannii (CRAB) in ICU of medical centers/regional hospitals was less than 20% in 2003, it rose to 70% in Q3 2010. The objective of this study is to investage the distribution of integron drug-resistant gene and OXA typing of carbapenemase in extensively drug-resisitant A. baumannii (XDRAB) isolates from XDRAB-HAIs cases (2008~2010, 25 months). We also used pulsed-field gel electrophoresis (PFGE) to investigate the linkage between XDRAB strains. The risk factors of XDRAB-HAIs were investigated using case-control study (case: control=1:4). The result shows that 23 of 25 XDRAB isolates habored class I integron with a 2300-kb gene cassette. None carries class II integron. Most isolates had carry OXA 23 (n=21, 84%) and OXA51 (n=25, 100%). PFGE showed a genetic diversity among the 25 XDRAB isolates. Univariate analysis showed that long-term bed rest, hemodialysis, tracheostomy, use of glycopeptide, use of imipenem or meropenem, use of anti-pseudomonal penicillins, and use of the fourth generation cephalosporins, are statistically significant risk factors. Multiple conditional logistic regression analysis showed that, after adjusting for the effect of other variables, long-term bed rest (adjusted odds ratio 5.2, 95%CI: 1.1–24.4) and use of imipenem, meropenem, anti-pseudomonal penicillins, or the fourth-generation cephalosporins (adjusted odds ratio 4.3, 95%CI: 1.4–12.7) remain independent risk factors. We concluded that, for XDRAB HAIs control, it is essential to emphasize the prudent use of board-spectrum antibiotics active against gram-negative bacteria.