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在西班牙北部,5 年内(2013-2017 年)幽门螺杆菌的抗菌药物耐药性及其与根除治疗的关系。

Helicobacter pylori antimicrobial resistance during a 5-year period (2013-2017) in northern Spain and its relationship with the eradication therapies.

机构信息

Department of Gastroenterology, Donostia University Hospital, San Sebastian, Spain.

Department of Microbiology, Donostia University Hospital-IIS Biodonostia, San Sebastian, Spain.

出版信息

Helicobacter. 2019 Feb;24(1):e12557. doi: 10.1111/hel.12557. Epub 2018 Nov 20.

DOI:10.1111/hel.12557
PMID:30460730
Abstract

BACKGROUND

Antibiotic resistance is the main cause for Helicobacter pylori therapy failure. Frequently, empirical regimens have been recommended in patients with various H. pylori eradication failures. In patients with H. pylori-resistant to various families of antibiotics, the treatment guided by antimicrobial susceptibility testing allows the achievement of good eradication rates.

AIM

To evaluate the effectiveness of susceptibility-guided antimicrobial treatment for H. pylori infection in patients with resistance to one or various families of antibiotics.

METHODS

A total of 3170 consecutive patients infected by H. pylori during 2013-2017 were tested for antimicrobial susceptibility. 66.6% patients showed resistance to one antimicrobial, 18.9% to two, and 2.4% to three families of antibiotics. A cohort of 162 H. pylori-positive patients were enrolled in this study. Forty-three with single H. pylori resistance to clarithromycin (CLR) were treated with omeprazole (PPI), amoxicillin (AMX), and levofloxacin (LVX)-OAL (31 subjects) or omeprazole, AMX, and metronidazole (MTZ)-OAM (12 patients) and 77 patients with dual H. pylori resistance (51 to CLR and MTZ, 12 to CLR plus LVX, and 14 to MTZ plus LVX) received OAL or OBTM (PPI, bismuth subcitrate, tetracycline, and MTZ), OAM, and OAC, respectively. Other 42 patients with triple H. pylori resistance (CLR, LVX, and MTZ) were treated with PPI, AMX, and rifabutin-OAR (18 subjects), PPI, AMX, and doxycycline-OAD (8), OADB (7), OBTM (6), and ODBR (3). All subjects received standard doses for 10 days. Eradication rate was confirmed by C-UBT. Adverse events were assessed by a questionnaire.

RESULTS

Intention-to-treat analysis demonstrates that eradication rates using triple therapies in patients with H. pylori resistance to one and to two families of antibiotics were 93% and 94.8%, respectively. In subjects with H. pylori-resistant to three families of antibiotics, cure rate was higher in naïve patients treated with OAR-10 days compared to those treated with bismuth-containing quadruple therapies (90% vs 75%). Adverse events were limited (18 of 162, 11.1%), all of them mild-moderate.

CONCLUSIONS

The implementation of susceptibility-guided triple therapy for 10 days leads to eradication rate ≥95% in naïve patients with H. pylori resistance to one or two families of antimicrobials. In naïve patients with H. pylori resistance to three families, OAR treatment achieved a 90% of eradication.

摘要

背景

抗生素耐药性是导致幽门螺杆菌治疗失败的主要原因。在各种幽门螺杆菌根除失败的患者中,通常推荐使用经验性治疗方案。对于对各种抗生素家族均耐药的幽门螺杆菌感染患者,根据抗菌药物敏感性试验进行指导的治疗可实现良好的根除率。

目的

评估针对对一种或多种抗生素家族耐药的幽门螺杆菌感染患者进行药敏指导抗菌治疗的有效性。

方法

对 2013-2017 年期间感染幽门螺杆菌的 3170 例连续患者进行了抗菌药物敏感性检测。66.6%的患者对一种抗生素耐药,18.9%对两种抗生素耐药,2.4%对三种抗生素耐药。本研究纳入了 162 例幽门螺杆菌阳性患者。43 例对克拉霉素(CLR)单耐药的患者接受了奥美拉唑(PPI)、阿莫西林(AMX)和左氧氟沙星(LVX)-OAL(31 例)或奥美拉唑、AMX 和甲硝唑(MTZ)-OAM(12 例)治疗,77 例对 CLR 和 MTZ 双重耐药(51 例)、CLR 和 LVX 双重耐药(12 例)、MTZ 和 LVX 双重耐药(14 例)的患者接受了 OAL 或 OBTM(PPI、柠檬酸铋、四环素和 MTZ)、OAM 和 OAC 治疗。其他 42 例对 CLR、LVX 和 MTZ 三重耐药的患者接受了 PPI、AMX 和利福布汀-OAR(18 例)、PPI、AMX 和多西环素-OAD(8 例)、OADB(7 例)、OBTM(6 例)和 ODBR(3 例)治疗。所有患者均接受标准剂量治疗 10 天。通过 C-UBT 确认根除率。通过问卷调查评估不良事件。

结果

意向治疗分析显示,对一种和两种抗生素家族耐药的幽门螺杆菌患者,三联疗法的根除率分别为 93%和 94.8%。在对三种抗生素家族耐药的患者中,与铋剂四联疗法相比,初次治疗的 OAR-10 天疗法对 OAR-10 天疗法的治疗成功率更高(90%比 75%)。不良事件有限(162 例中的 18 例,11.1%),均为轻中度。

结论

在对一种或两种抗生素家族耐药的初次治疗患者中,实施 10 天的药敏指导三联疗法可使根除率≥95%。在对三种抗生素家族耐药的初次治疗患者中,OAR 治疗的根除率达到 90%。

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