亞太地區幽門螺旋桿菌原發性抗藥性的趨勢

Abstract

背景 近年來的研究，將幽門螺旋桿菌視為與胃癌有高度相關的感染性疾病;有效的治療幽門螺旋桿菌，可以大幅降低胃癌的發生率。然而，近年來幽門螺旋桿菌發生抗藥性的比例大幅增高，因而降低第一線抗生素殺菌的成功率。因此，針對各地區的幽門螺旋桿菌抗藥性型態，選擇當地合適的第一線抗生素，是非常重要且刻不容緩的公衛議題;然而，目前亞太地區缺乏完整及廣泛性幽門螺旋桿菌抗藥性型態及第一線抗生素療效的探討。因此，本研究的目的就是希望透過系統性文獻回顧及統合分析，進而提供亞太地區內的所有國家關於幽門螺旋桿菌抗藥性型態的變化與現況，並給予選擇第一線殺菌用藥的建議。 方法 本研究是透過PubMed資料庫搜尋從西元1990年1月至2016年9月期間所有刊登的文章及近五年於國際會議發表的摘要，文章不論是屬於何種研究設計，只要內容符合原發性幽門螺桿菌抗藥性的納入標準，即可收入做後續的資料分析; 至於幽門螺旋桿菌第一線治療根除率的分析，只納入研究設計屬於隨機對照試驗的文章。考量到現實上研究間會存在異質性的可能性，我們選擇隨機效應模式去做統合分析，並會根據不同的國家及不同的收案時間，做進一步的次群組分析。 結果 關於原發性幽門螺桿菌抗藥性的分析，總共有149篇文章來至於亞太地區的24個國家，其結果顯示亞太地區整體clarithromycin抗藥性比率為16% (95%信賴區間為14-18%)，metronidazole抗藥性比率為44% (95%信賴區間為39-49%)，levofloxacin抗藥性比率為17% (95%信賴區間為14-21%)，amoxilline抗藥性比率為3% (95%信賴區間為2-5%)，及tetracycline抗藥性比率為4% (95%信賴區間為3-6%)。根據不同收案時間的次群組分析結果，我們發現clarithromycin與levofloxacin的抗藥性，有隨著時間進展不斷往上爬升的趨勢; 反之，其他四種抗生素並未有太大幅度的變動。至於幽門螺旋桿菌一線治療根除率的分析，總共有158篇文章來至於亞太地區的16個國家，其結果顯示多數的第一線殺菌處方其殺菌效果，皆隨著時間有逐步變差的趨勢，特別是clarithromycin為主的三合一療法，其療效在大多數的亞太地區國家，都呈現非常不理想的根除率。 結論 亞太地區的原發性幽門螺桿菌抗藥性型態有著極大的差異性，因此，關於幽門螺旋桿菌第一線治療藥物的選擇，必須因地制宜選擇當地合適的處方。除此之外，針對亞太地區clarithromycin與levofloxacin抗藥性不斷爬升的警訊，各國必須有策略性的做進一步的控制與監控。

Background A comprehensive systemic review and meta-analysis of the prevalence of primary antibiotic resistance of Helicobacter pylori (H. pylori) and the efficacies of first-line regimens for H. pylori eradication is lacking in Asia-Pacific. We aimed to assess the trends in the primary H. pylori antibiotic resistance and their relations to eradication rates of first-line therapies in this region. Methods We searched PubMed for published articles between January 1990 to September 2016 and abstracts from international conferences. Both observational articles and randomised controlled trials (RCTs) that reported primary H. pylori antibiotic resistance and only RCTs that evaluated the eradication rates of first-line therapies in Asia-Pacific were seperately included for meta-analysis under random effect model. Subgroup analyses by countries and study periods were undertaken to determine a trend change of country-specific prevalence of primary antibiotic resistance and efficacies of first-line therapies over time. Results One hundred and forty-nine articles from 24 countries were included for resistance analysis. The overall prevalence of primary H. pylori resistance in Asia-Pacific were 16% (95% CI 14%-18%) for clarithromycin, 44% (95% CI 39%-49%) for metronidazole, 17% (95% CI 14%-21%) for levofloxacin, 3% (95% CI 2%-5%) for amoxicillin, and 4% (95% CI 3%-6%) for tetracycline. We observed a rising trend in clarithromycin and levofloxacin resistance, whereas the resistance rates of other antibiotics remained stable. For the efficacies of first-line therapies, 158 articles from 16 countries were included. A declining trend in cure rate of most first-line regimens and unsatisfied efficacy of clarithromycin-based triple therapy in most countries was observed. Conclusions The prevalences of primary antibiotic resistance varied greatly in Asia-Pacific and treatment strategy should be adapted to each country. Besides, strategies to control the alarming rise of the clarithromycin and levofloxacin resistance in the Asia-Pacific region are also warranted.