新興革蘭氏陰性致病菌造成之壞死性筋膜炎: 系統性回顧及統合分析

Abstract

背景：壞死性筋膜炎是一種導致嚴重軟組織感染以及壞死的疾病。近年來，發現在台灣和一些位於西太平洋的國家，越多由單一革蘭氏陰性菌所感染的壞死性筋膜炎相關的研究被發表出來，像是創傷弧菌、親水性產氣單胞菌、克雷伯氏肺炎菌，是因為西太平洋地區的醫生對於此類的研究比較有興趣，還是微生物學上的地理分布上真的有所不同，故藉由系統性回顧及統合分析來區別以上兩種假說。 方法：在論文資料庫Pubmed與EMBASE使用關鍵字進行搜尋在2019年1月31日前與壞死性筋膜炎有關的所有論文，由訂定的納入及排除條件進行系統性回顧，統合分析病患感染之細菌種類、因病死亡率以及糖尿病和肝硬化人數，以比例的方式呈現，將盛行率先以double arcsine transformation做轉換，再以random effect model估計加權平均值及組間差異。 結果：收錄一共189篇論文進行統合分析，依照WHO將世界分為六大區域，發現相較於其他五個地理區域地區，西太平洋地區在由創傷弧菌 (Vibrio vulnificus) 2.77% (範圍：0%-59.6%)、親水性產氣單胞菌 (Aeromonas hydrophila) 0.68% (範圍：0%-13.3%)、克雷伯氏肺炎菌 (Klebsiella pneumoniae) 2.54% (範圍：0%-33.3%)所感染的壞死性筋膜炎病患比例的加權平均值相較於其他五個地理區域在統計上顯著較高，尤其是台灣西部沿海、香港及，但區域內部及國家內部異質性極高。 結論：壞死性筋膜炎的微生物學存在著地理上的差異。在西太平洋地區，特別是台灣，新興的革蘭氏陰性菌，創傷弧菌、親水性產氣單胞菌、克雷伯氏肺炎菌已成為壞死性筋膜炎重要的致病原。

Introduction: Necrotizing fasciitis (NF) has been defined as a life-threatening severe soft-tissue infection. In recent 20 years, monomicrobial NF cases caused by gram-negative bacteria, like Vibrio vulnificus, Aeromonas hydrophila, and Klebsiella pneumoniae, have been reported and confirmed in Taiwan and other western Pacific countries. It remains unknown whether the apparently emergence of gram-negative NF in western pacific region is the results of selectively reporting of cases with curiosity, or, on the contrary, there is a genuine geographic difference in microbiology of NF. Therefore, we aimed to these two hypotheses by systematic review and meta-analysis. Methods: The systematic review has been registered in PROSPERO. (PROSPERO CRD42018096653). Before January 31, 2019, we identified all eligible studies through searching along with reports completed in the research registry database. Followed inclusion and exclusion criteria to searched and included research. For meta-analysis, proportion of specific bacteria in different geographic area first underwent double arcsine transformation. We then estimated the weighted mean and subgroup difference using random effect model. Results: After systematic review, we include 189 articles, and divide the world into six regions according to WHO, we found that the weighted mean of the proportions of necrotizing fasciitis patient infected by V. vulnificus 2.77% (range: 0%-59.6%), A. hydrophila 0.68% (range: 0%-13.3%), K. pneumoniae 2.54% (range: 0%-33.3%) in Western Pacific region were significantly higher than other regions, especially west coast of Taiwan, Hong Kong, and South Korea. However, large heterogeneity existed both within regions and within countries. Conclusion: Geographic difference exists in microbiology of NF. Emerging gram-negative pathogenic bacteria are already important causal microorganisms in Western Pacific region, particularly Taiwan.