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基于质子泵抑制剂的1周三联疗法治疗失败后幽门螺杆菌对抗生素继发耐药的发生率:一项前瞻性研究

Incidence of secondary Helicobacter pylori resistance to antibiotics in treatment failures after 1-week proton pump inhibitor-based triple therapies: a prospective study.

作者信息

Pilotto A, Franceschi M, Rassu M, Leandro G, Bozzola L, Furlan F, Di Mario F

机构信息

Department of Geriatrics, S. Bortolo Hospital, Vicenza, Italy.

出版信息

Dig Liver Dis. 2000 Nov;32(8):667-72. doi: 10.1016/s1590-8658(00)80327-8.

Abstract

BACKGROUND

Antibiotic-resistant Helicobacter pylori strains are becoming increasingly prevalent, although it is not clear to what extent the new resistant organisms will spread.

AIM

To evaluate the incidence of secondary Helicobacter pylori resistance to metronidazole, clarithromycin and/or amoxycillin after one-week proton pump inhibitor based triple therapy failure in patients who were, before therapy infected with Helicobacter pylori strains susceptible to these antibiotics.

PATIENTS AND METHODS

Enrolled in the study were 97 consecutive Helicobacter pylori-positive subjects infected by Helicobacter pylori strains susceptible to metronidazole, clarithromycin and amoxycillin. Activity of tested antibiotics was determined by means of the E-test. Patients were treated for seven days with a proton pump inhibitor, omeprazole 20 mg twice daily or pantoprazole 40 mg once daily, plus clarithromycin 250 mg twice daily and metronidazole 250 mg four times daily; or with a proton pump inhibitor plus amoxycillin 1 g twice daily and clarithromycin 500 mg twice daily. Two months after completion of therapy, endoscopy and gastric biopsies for histology, rapid urease test and culture were repeated.

RESULTS

Four patients were dropped from the study Overall Helicobacter pylori cure rates expressed as both intention-to-treat and per-protocol analyses, were, respectively 80% (40/50) and 81.6% (40/49) with proton pump inhibitor, clarithromycin and metronidazole and 76.6% (36/47) and 81.8% (36/44) with proton pump inhibitor amoxycillin and clarithromycin. No significant differences were observed between the two treatments. Subjects in whom treatment failed were significantly younger and had less active ulcer than cured patients. Of treatment failures, 70.6% (12 out of 17 subjects) de veloped a secondary resistance to metronidazole (35.33% and/or clarithromycin (64.7%). Secondary antibiotic resistance occurred in 77. 8% of treatment failures treated with proton pump inhibitor, clarithromycin and metronidazole and in 62.5% of those treated with proton pump inhibitor, amoxycillin and clarithromycin. Considering all patients treated, the overall incidence of secondary metronidazole and/or clarithromycin resistance after therapy was reported in 12.9% of subjects (12 out of 93 treated patients).

CONCLUSIONS

Secondary Helicobacter pylori resistances to metronidazole and/or clarithromycin occurred in large percentages in patients with treatment failure after the one-week proton pump inhibitor-based triple therapies, proton pump inhibitor, clarithromycin and metronidazole and proton pump inhibitor, amoxycillin and clarithromycin. It is likely that new antibiotics or treatment strategies will be needed in the near future to successfully treat Helicobacter pylori infection.

摘要

背景

尽管尚不清楚新的耐药菌将在多大程度上传播,但耐抗生素的幽门螺杆菌菌株正变得越来越普遍。

目的

评估在治疗前感染对这些抗生素敏感的幽门螺杆菌菌株的患者中,基于质子泵抑制剂的三联疗法治疗一周失败后,幽门螺杆菌对甲硝唑、克拉霉素和/或阿莫西林产生继发性耐药的发生率。

患者和方法

连续纳入97名幽门螺杆菌阳性受试者,这些受试者感染的幽门螺杆菌菌株对甲硝唑、克拉霉素和阿莫西林敏感。通过E试验测定受试抗生素的活性。患者接受为期7天的治疗,使用质子泵抑制剂,奥美拉唑20mg每日两次或泮托拉唑40mg每日一次,加克拉霉素250mg每日两次和甲硝唑250mg每日四次;或使用质子泵抑制剂加阿莫西林1g每日两次和克拉霉素500mg每日两次。治疗结束两个月后,重复进行内镜检查和胃活检以进行组织学、快速尿素酶试验和培养。

结果

4名患者退出研究。以意向性分析和符合方案分析表示的总体幽门螺杆菌治愈率,使用质子泵抑制剂、克拉霉素和甲硝唑时分别为80%(40/50)和81.6%(40/49),使用质子泵抑制剂、阿莫西林和克拉霉素时分别为76.6%(36/47)和81.8%(36/44)。两种治疗方法之间未观察到显著差异。治疗失败的受试者明显比治愈的患者年轻,溃疡活动程度也较低。在治疗失败的受试者中,70.6%(17名受试者中的12名)对甲硝唑产生继发性耐药(35.33%)和/或对克拉霉素产生继发性耐药(64.7%)。在使用质子泵抑制剂、克拉霉素和甲硝唑治疗失败的患者中,77.8%发生继发性抗生素耐药,在使用质子泵抑制剂、阿莫西林和克拉霉素治疗失败的患者中,62.5%发生继发性抗生素耐药。考虑所有接受治疗的患者,治疗后甲硝唑和/或克拉霉素继发性耐药的总体发生率在12.9%的受试者中报告(93名接受治疗的患者中的12名)。

结论

在基于质子泵抑制剂的一周三联疗法(质子泵抑制剂、克拉霉素和甲硝唑以及质子泵抑制剂、阿莫西林和克拉霉素)治疗失败的患者中,幽门螺杆菌对甲硝唑和/或克拉霉素产生继发性耐药的比例很高。在不久的将来,可能需要新的抗生素或治疗策略来成功治疗幽门螺杆菌感染。

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