目的
三重抗藥性(Clarithromycin, Metronidazole, Levofloxacin)幽門桿菌是臨床上棘手的問題。過去臨床指引並沒有明確的指示在做完藥物敏感性測試後該如何選擇下一步救援治療的處方也就是第三線的抗生素用藥，導致過去幽門桿菌救援治療的成功率不高。此研究目的是希望透過成大醫院過去治療的經驗來找出更為理想的抗生素有效濃度切點來選擇救援治療。
逆流性食道炎容易好發在幽門桿菌除菌後。難治型逆流性食道炎更是臨床的難題。在胃鏡採檢的過程，我們同時研究食道微生物菌相在難治型逆流性食道炎患者的變化，希望利於這類患者未來在治療上有所突破。
方法
本研究回顧過去430位接受幽門桿菌藥物敏感性測試患者，其中共有73位病人(17%)符合三重抗藥性幽門桿菌 (最小抑菌濃度clarithromycin > 0.5 mg/L, levofloxacin > 1 mg/L, metronidazole > 8 mg/L)。其中有69位患者根據胃腸科醫師個人當下決定給予ATBP(amoxicillin, tetracycline, bismuth, proton pump inhibitor)或是MTBP(metronidazole, tetracycline, bismuth, proton pump inhibitor)，療程7~14天。其中有14位患者經過尿素吹氣測試，仍舊治療失敗者，會交叉接受另一種幽門桿菌治療。
在驗證研究中，利用回顧性研究得到的結果，設計了一套救援治療制定的流程圖，並且於2020年時收案13位多重抗藥性幽門桿菌患者。分析其成效。
在食道微生物菌相研究，我們透過問卷分數和質子幫浦阻斷劑使用後的治療反應來把病人區分成對照組(control)、反應良好組(GERD)和難治型組(Refractory GERD)各組都是6人。透過胃鏡檢查蒐集遠端食道檢體來進行菌相分析。
結果
回顧性研究中，在第一次的救援治療中，治療成功率為59.4%，MTBP除菌率高於ATBP組 (Intention-to-treat (ITT) 分析, 70.3% vs. 46.9%, p = 0.048; Per protocol (PP)分析, 79.5% vs. 51.7%, p = 0.037)。進一步分析發現在MTBP組別中，抗生素使用達到14天(p = 0.037)和tetracycline的最小抑菌濃度 ≤ 0.094 mg/L (p < 0.001) 會達到較高的除菌成功率。在ATBP組別中，amoxicillin最小抑菌濃度 ≤ 0.032 mg/L則會達成更高的除菌效果(72.2 vs. 33.3%, p = 0.025)，交叉治療後除菌率達57.1%。總體而言，1st ATBP / 2nd MTBP和1st MTBP / 2nd ATBP治療上沒有差異性(69.0% vs. 87.9%, p值 = 0.068)
在驗證研究中，我們發現透過這樣重新制定的amoxicillin和tetracycline有效抑菌濃度切點所選擇出來的有效抗生素組合能夠大幅改善救援治療的除菌成功率 (85%)高於回顧中第一次的救援治療(59.4%)。
在食道菌相研究中，我們發現在難治型組中有較高比例的Streptococcus, Roseburia和Clostridium_XIVa genus。
結論
調整過後的amoxicillin和tetracycline最小抑菌濃度切點能夠成功預測在救援治療選擇ATBP或是MTBP的成功率。同時在食道逆流使用難治型組則觀察到有較高比例的Streptococcus, Roseburia和Clostridium_XIVa。

The study aimed to figure out the better MIC (minimal inhibitory concentration) breakpoint of antibiotics to predict the success of rescue therapy. Refractory reflux symptoms was difficult for management . During the endoscopy, we also performed the distal esophageal mucosal biopsy to investigate whether specific microbiota cause.The study enrolled 73 patients (17%) who suffered from triple drug resistant (clarithromycin > 0.5 mg/L, levofloxacin > 1 mg/L, metronidazole > 8 mg/L) H. pylori infection after reviewing 430 H. pylori infected patients who experienced eradication failure in decades. Among them, 69 patients received ATBP(amoxicillin, tetracycline, bismuth, proton pump inhibitor) or MTBP(metronidazole, tetracycline, bismuth, proton pump inhibitor). In the MTBP group, the treatment duration up to 14 days (p=0.037) and tetracycline MIC ≤ 0.094 mg/L (p < 0.001) predicted the better outcome. In the ATBP group, amoxicillin MIC ≤ 0.032 mg/L predicted the better outcome (72.2 vs. 33.3%, p = 0.025). In the microbiota study, the distal esophagus showed higher proportion of Bacteroides (38.1%), Lachnospiraceae (16.3%) and Roseburia (12.8%). From the Metastat analysis, the refractory group showed more Streptococcus, Roseburia和Clostridium_XIVa.

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