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大剂量质子泵抑制剂、阿莫西林和强力霉素三联疗法对根除幽门螺杆菌无效:一项概念验证研究。

Triple therapy with high-dose proton-pump inhibitor, amoxicillin, and doxycycline is useless for Helicobacter pylori eradication: a proof-of-concept study.

作者信息

Almeida Nuno, Romãozinho José M, Donato Maria M, Luxo Cristina, Cardoso Olga, Cipriano Maria A, Marinho Carol, Sofia Carlos

机构信息

Gastroenterology Department, Coimbra University Hospital, Coimbra, Portugal.

出版信息

Helicobacter. 2014 Apr;19(2):90-7. doi: 10.1111/hel.12106. Epub 2014 Feb 10.

Abstract

INTRODUCTION

Helicobacter pylori resistance to antibiotics is steadily increasing and multidrug-resistant strains are common and difficult to eliminate, mainly in countries where bismuth, tetracycline, furazolidone, and rifabutin are unavailable.

AIM

To evaluate the efficacy and safety of a triple therapy with proton-pump inhibitor (PPI), amoxicillin, and doxycycline in patients with multidrug-resistant H. pylori.

PATIENTS AND METHODS

This prospective study involved 16 patients (13 females; mean age - 50 ± 11.3 years) infected by H. pylori with known resistance to clarithromycin, metronidazole, and levofloxacin, but susceptibility to amoxicillin and tetracycline. All patients were previously submitted to upper endoscopy with gastric biopsies for H. pylori culture and susceptibility testing by Etest. Mutations in 23S rRNA and gyrA genes were determined by real-time PCR. A 10-day eradication regimen with PPI (double-standard dose b.i.d.), amoxicillin (1000 mg b.i.d.), and doxycycline (100 mg b.i.d.) was prescribed after pretreatment with PPI during 3 days. Eradication success was assessed by (13) C-urea breath test 6-10 weeks after treatment. Compliance and adverse events were determined through phone contact immediately after treatment and specific written questionnaires.

RESULTS

Only one patient did not complete treatment due to adverse events. Another four patients experienced mild side effects not affecting compliance. The control (13) C-urea breath test was positive in all patients. Per-protocol and intention-to-treat eradication rates were 0%.

CONCLUSIONS

Although safe, a triple-therapy protocol with high-dose PPI, amoxicillin, and doxycycline is useless for multidrug-resistant H. pylori eradication.

摘要

引言

幽门螺杆菌对抗生素的耐药性正在稳步上升,多重耐药菌株很常见且难以消除,主要在无法获得铋剂、四环素、呋喃唑酮和利福布汀的国家。

目的

评估质子泵抑制剂(PPI)、阿莫西林和强力霉素三联疗法对多重耐药幽门螺杆菌患者的疗效和安全性。

患者与方法

这项前瞻性研究纳入了16例患者(13例女性;平均年龄50±11.3岁),这些患者感染了已知对克拉霉素、甲硝唑和左氧氟沙星耐药,但对阿莫西林和四环素敏感的幽门螺杆菌。所有患者此前均接受过上消化道内镜检查及胃活检,以进行幽门螺杆菌培养和Etest药敏试验。通过实时PCR测定23S rRNA和gyrA基因的突变情况。在3天的PPI预处理后,给予10天的根除方案,包括PPI(双倍标准剂量,每日两次)、阿莫西林(1000 mg,每日两次)和强力霉素(100 mg,每日两次)。治疗后6 - 10周通过¹³C - 尿素呼气试验评估根除成功率。通过治疗后立即电话联系和特定的书面问卷确定依从性和不良事件。

结果

仅有1例患者因不良事件未完成治疗。另外4例患者出现轻度副作用,但不影响依从性。所有患者的对照¹³C - 尿素呼气试验均为阳性。符合方案分析和意向性分析的根除率均为0%。

结论

尽管高剂量PPI、阿莫西林和强力霉素的三联疗法安全,但对多重耐药幽门螺杆菌的根除无效。

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