基因型耐药导向与经验性治疗难治性幽门螺杆菌感染的疗效比较。

PubMed ID
发表日期 2018年10月

原始出处 胃肠病学
Gastroenterology
作者 Liou  Jyh-Ming  Chen  Po-Yueh  Luo  Jiing-Chyuan  Lee  Ji-Yuh  Chen  Chieh-Chang  Fang  Yu-Jen  Yang  Tsung-Hua  Chang  Chi-Yang  Bair  Ming-Jong  Chen  Mei-Jyh  Hsu  Yao-Chun  Hsu  Wen-Feng  Chang  Chun-Chao  Lin  Jaw-Town  Shun  Chia-Tung  El-Omar  Emad M  Wu  Ming-Shiang 

文献标题 基因型耐药导向与经验性治疗难治性幽门螺杆菌感染的疗效比较。
Efficacies of Genotypic Resistance-Guided vs Empirical Therapy for Refractory Helicobacter pylori Infection.

文献摘要 BACKGROUND & AIMS

我们的目的是在随机对照试验中比较基因型耐药导向治疗和经验性治疗根除难治性幽门螺杆菌感染的疗效。

METHODS

从2012年10月到2017年9月,我们在台湾进行了两项多中心、开放性试验,研究对象为幽门螺杆菌感染(20岁或以上)患者,之前两种或两种以上治疗方案均失败。将患者随机分为两组,分别给予基因型耐药导向治疗14天(试验1中n=21,试验2中n=205)或根据用药史给予经验性治疗14天(试验1中n=20,试验2中n=205)。患者在前7天接受含埃索美拉唑和阿莫西林的序贯治疗,随后接受埃索美拉唑和甲硝唑、左氧氟沙星、克拉霉素或四环素(试验1中为强力霉素,根据胃活检标本(A组)或根据用药史进行的经验性治疗确定的耐药基因型标志物,再服用7天(每天两次)。用聚合酶链反应直接测序法鉴定了23S核糖体RNA或旋转酶A的耐药相关突变。通过13C尿素呼气试验确定根除情况。主要结果是根除率。

RESULTS

试验1中,接受基因型耐药指导治疗的21例患者中有17例(81%)根除了幽门螺杆菌感染,接受经验性治疗的20例患者中有12例(60%)根除了幽门螺杆菌感染(P=0.181)。由于给予强力霉素序贯治疗的患者根除率低(26例中15例[57.7%]),本试验提前终止。在试验2中,根据意向治疗分析,205例接受基因型耐药指导治疗的患者中,160例(78%)根除了幽门螺杆菌感染,205例接受经验性治疗的患者中,148例(72.2%)根除了幽门螺杆菌感染(P=0.170)。两组间不良反应发生率和依从性无显著差异。

CONCLUSIONS

在考虑可及性、成本和患者偏好的基础上,基于用药史设计合理的经验性治疗是基因型耐药导向治疗根除难治性幽门螺杆菌感染的可接受的替代方法。临床试验.gov编号:NCT01725906。


BACKGROUND & AIMS

We aimed to compare the efficacy of genotypic resistance-guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials.

METHODS

We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance-guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate.

RESULTS

H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance-guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P = .181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance-guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups.

CONCLUSIONS

Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance-guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.


获取全文 10.1053/j.gastro.2018.06.047