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影响幽门螺杆菌一线三联疗法的因素包括 CYP2C19 基因型和抗生素耐药性。

Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance.

机构信息

Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, South Korea.

出版信息

Dig Dis Sci. 2014 Jun;59(6):1235-43. doi: 10.1007/s10620-014-3093-7. Epub 2014 Mar 6.

Abstract

BACKGROUND

Emerging evidence shows that the eradication rate of proton pump inhibitor (PPI)-based triple therapy for the first-line treatment of Helicobacter pylori (H. pylori) has decreased.

AIMS

To clarify the trend of eradication rate of PPI-based triple therapy and to assess the related factors in Korea during the past decade.

METHODS

We prospectively prescribed the triple regimen for seven days (PPI + amoxicillin 1.0 g + clarithromycin 500 mg, twice a day) from March 2003 to May 2013 in 2,202 H. pylori-positive patients. Antibiotic susceptibility tests were performed by the agar dilution method, and the CYP2C19 genotype was determined by the PCR method.

RESULTS

In the past decade, the annual eradication rate showed a decreasing trend in intention-to-treat and per-protocol analyses (P = 0.001, both). The antibiotic resistance was increased to amoxicillin (7.2-17.2%, P = 0.003) and clarithromycin (23.2-37.3%, P = 0.010) during the study period. The poor metabolizer genotype of CYP2C19 showed a high eradication rate compared to the extensive metabolizer (86.8 vs. 78.2%, P = 0.035). In addition, age ≥ 50 years, female gender, BMI < 25 kg/m(2), amoxicillin and/or clarithromycin resistance were associated with treatment failure on univariate analysis. However, on multivariate analysis, clarithromycin resistance was the only significant factor for treatment failure (OR, 12.76; 95% CI, 5.58-29.18; P < 0.001).

CONCLUSIONS

An increase in clarithromycin resistance has led to decreased eradication rate of first-line triple therapy, and; hence, a new strategy is needed to improve the eradication rate of H. pylori.

摘要

背景

新出现的证据表明,质子泵抑制剂(PPI)三联疗法作为一线治疗幽门螺杆菌(H. pylori)的根除率有所下降。

目的

阐明过去十年韩国 PPI 三联疗法根除率的趋势,并评估相关因素。

方法

我们前瞻性地在 2202 例 H. pylori 阳性患者中,于 2003 年 3 月至 2013 年 5 月,采用为期 7 天的三联方案(PPI+阿莫西林 1.0 g+克拉霉素 500 mg,每日 2 次)进行治疗。采用琼脂稀释法进行抗生素药敏试验,采用 PCR 法测定 CYP2C19 基因型。

结果

在过去十年中,意向治疗和按方案分析的年度根除率均呈下降趋势(P = 0.001,均)。在研究期间,阿莫西林(7.2%-17.2%,P = 0.003)和克拉霉素(23.2%-37.3%,P = 0.010)的抗生素耐药率升高。CYP2C19 的弱代谢基因型与广泛代谢型相比,根除率较高(86.8%比 78.2%,P = 0.035)。此外,年龄≥50 岁、女性、BMI<25 kg/m²、阿莫西林和/或克拉霉素耐药,在单变量分析中与治疗失败相关。然而,在多变量分析中,克拉霉素耐药是治疗失败的唯一显著因素(OR,12.76;95%CI,5.58-29.18;P<0.001)。

结论

克拉霉素耐药率的增加导致一线三联疗法根除率下降,因此需要新的策略来提高 H. pylori 的根除率。

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