上海市单中心儿童幽门螺杆菌不同治疗方案根除率及其耐药率的横断面调查

目的:考察上海市儿童幽门螺杆菌常用治疗方案的根除率和幽门螺杆菌的耐药率。方法:回顾性收集复旦大学附属儿科医院(我院)2014年1月1日至2017年9月19日门诊内镜诊断幽门螺杆菌感染、完成1个治疗方案(2周)且随访幽门螺杆菌根除情况的病例,从我院电子病历系统中截取性别、诊断年龄、主诉、内镜表现、尿素酶试验(RUT)结果、病理检查、胃黏膜培养及药敏结果、治疗方案和疗程等。完成1个治疗方案1个月后来我院行尿素呼气试验(UBT)或胃镜RUT检测,其中1项阴性判断为幽门螺杆菌根除。结果:1558例确诊幽门螺杆菌感染患儿进入本文分析,平均年龄(8.5±3.1)岁,男性56.5%,腹部不适主诉占74.6%,非溃疡病变占85.0%。均为经验性治疗且均完成了标准治疗时间。一线治疗+补救治疗根除率56.7%(883/1558),其中一线治疗和补救治疗根除率分别为56.4%(751/1331)和58.1%(132/227),差异无统计学意义。一线治疗中奥美拉唑(OME)+克拉霉素(CLA)+阿莫西林(AMO)/阿莫西林-克拉维酸钾(AMOc)、OME+CLA+甲硝唑(MET)和其他治疗方案根除率分别为57.9%(659/1139)、31.8%(34/107)和68.2%(58/85),OME+CLA+MET治疗方案根除率低于其他治疗方案;补救治疗中,铋+OME+CLA+AMO/AMOc、铋+OME+CLA+MET和其他治疗方案根除率分别为57.6%(87/151)、52.3%(23/44)和68.8%(22/32),两两比较差异无统计学意义。幽门螺杆菌培养阳性579株菌株中,CLA、MET和AMO的耐药率分别为31.8%、45.1%和1.4%;CLA和MET同时耐药率为23.0%。根除(一线+补救)治疗失败和治疗成功分别为259和320例,根除治疗失败病例的CLA耐药率(44.0%vs21.9%)、MET耐药率(52.5%vs39.1%)和CLA+MET同时耐药率(32.4%vs15.3%)均显著高于根除治疗成功病例,差异均有统计学意义。一线和补救治疗分别为475和104例,CLA、MET和CLA+MET同时耐药率分别为(29.5%vs42.3%)、(42.7%vs55.8%)和(20.4%vs34.6%),差异均有统计学意义。结论:因为CLA、MET高耐药等原因,儿童标准三联疗法的根除率只有56.4%,可能不适合在临床上作为幽门螺杆菌的一线治疗方案继续使用。但改善患儿服药依从性、提高药物剂量(如质子泵抑制剂和AMO)等是否可以提高标准三联疗法的根除率还有待进一步研究。

Compare the efficacy of different regimens for Helicobacter pylori infected children and investigate antimicrobial resistance in Shanghai: A cross-sectional study from a large tertiary center

Objective To investigate the efficacy of eradication therapy and antimicrobial resistance rate of Helicobacter pylori (H.pylori) strains among children in Shanghai.Methods From 1st January 2014 to 19th September 2017, patients who were diagnosed as H.pylori infection, completed the eradication therapy and reassessed the H.pylori status in Children's Hospital of Fudan University were enrolled in the restrospective study. All data were extracted from medical record system of the hospital including sex, age at diagnosis, endoscopy findings, rapid urease test (RUT) results, histology findings, microbiological culture with anti-microbial susceptibility results, treatment composition and duration. H. pylori infection was evaluated at least 4 weeks after the completion of the treatment. Negative urea breath test (UBT) or RUT was indicated successful eradication.Results A total of 1 558 patients with the mean age of (8.5±3.1) years and male of 56.5% were enrolled in the study. Abdominal discomfort and non-ulcer disease were common manifestations occurred in 74.6% and 85.0% of the patients, respectively. All patients received the empiric treatment for two weeks (10 days for sequential therapy). Total eradication rate in first-line and rescue therapy was 56.7%(883/1 558). The successful eradication rate was 56.4%(751/1 331) in first-line therapy and 58.1%(132/227) in rescue therapy. No significant difference was observed between the two groups. For first-line therapy, the eradication rate was 57.9% (659/1 139) in OCA/OCAc therapy (omeparaole, clarithromycin and amoxicillin/amoxicillin-clavulanic acid), 31.8%(34/107) in OCM therapy (omeparaole, clarithromycin and metronidazole) and 68.2%(58/85) in other therapies. The eradication rate of OCM therapy was lower than that of the other two groups. For rescue therapy, the eradication rate was 57.6%(87/151) in OCA/OCAc therapy with bismuth, 52.3%(23/44) in OCM therapy with bismuth and 68.8%(22/32) in other therapies. No significant difference was observed among each two groups. The resistance rates to clarithromycin, metronidazole and amoxicillin in 579 strains were 31.8%, 45.1% and 1.4%, respectively. Double resistance rates to clarithromycin and metronidazole were 23.0%. There were 259 strains in successful theatment group and 320 strains in treatment failure group. The latter got higher resistance rates in clarithromycin (44.0% vs 21.9%), metronidazole (52.5% vs 39.1%) and double resistance (32.4% vs 15.3%). Four hundred and seventy-five strains were in first-line therapy group and 104 strains in rescue therapy group. The resistance rates in rescue therapy group were all higher than that in first-line therapy group with clarithromycin (42.3% vs 29.5%), metronidazole (55.8% vs 42.7%) and double resistance (34.6% vs 20.4%).Conclusion The eradication rate of standard triple therapy in children was only 56.4% because of the high resistance in clarithromycin and metronidazole. It may not be suitable as the first-line therapy in clinical practice. Whether increasing the compliance of the patients and the dose of drugs (PPI and amoxicillin) will improve the eradication rate needs further investigation.