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中华实验和临床感染病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (03) : 178 -184. doi: 10.3877/cma.j.issn.1674-1358.2022.03.006

论著

两种含铋四联方案治疗幽门螺杆菌感染根除后复发疗效及其影响因素
杨雁慧1,(), 许彤丽1, 史淑利1   
  1. 1. 100040 北京,清华大学玉泉医院(清华大学中西医结合医院)
  • 收稿日期:2021-09-21 出版日期:2022-06-15
  • 通信作者: 杨雁慧

Two bismuth-containing quadruple regimens on treatment of recurrent Helicobacter pylori infection and the influencing factors

Yanhui Yang1,(), Tongli Xu1, Shuli Shi1   

  1. 1. Departmen of Gastroenterology, Tsinghua University Yuquan Hospital, Beijing 100040, China
  • Received:2021-09-21 Published:2022-06-15
  • Corresponding author: Yanhui Yang
引用本文:

杨雁慧, 许彤丽, 史淑利. 两种含铋四联方案治疗幽门螺杆菌感染根除后复发疗效及其影响因素[J/OL]. 中华实验和临床感染病杂志(电子版), 2022, 16(03): 178-184.

Yanhui Yang, Tongli Xu, Shuli Shi. Two bismuth-containing quadruple regimens on treatment of recurrent Helicobacter pylori infection and the influencing factors[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(03): 178-184.

目的

评价两种含铋四联疗法对幽门螺杆菌感染根除后复发治疗的有效性、安全性及影响因素。

方法

应用前瞻性、随机对照研究的方法,将清华大学玉泉医院(清华大学中西医结合医院)2017年3月至2020年9月收治的幽门螺杆菌感染根治后复发的95例患者应用随机信封法,分为研究组(45例)和对照组(50例),其中伴有萎缩性胃炎者分别为31例和28例。分别按照以莫西沙星为基础的含铋四联(胶体果胶铋200 mg、2次/d +雷贝拉唑10 mg、2次/d +阿莫西林1.0 g、2次/d +莫西沙星0.4 g、1次/d)和以甲硝唑为基础的含铋四联方案(胶体果胶铋200 mg、2次/d +雷贝拉唑10 mg、2次/d +阿莫西林1.0 g、2次/d +甲硝唑0.4 g、3次/d)均治疗2周。治疗结束4~8周,两组患者行13C尿素呼气试验。采用卡方检验分析幽门螺杆菌根除率、伴有萎缩性胃炎患者的根治率以及治疗后4周药物不良反应发生率。采用单因素分析和多因素Logistic回归分析筛选影响幽门螺杆菌感染根除后复发治疗的影响因素。

结果

研究组45例患者完成复发后治疗,37例患者幽门螺杆菌感染根除成功,意向性治疗分析(ITT)根治率和符合方案(PP)根治率分别为82.22%(37/45)和94.87%(37/39)。对照组50例患者完成复发后治疗,42例根除成功,ITT和PP根治率分别为82.22%(42/50)和87.5%(42/48)。两组患者ITT根治率(χ2 = 0.783、P = 0.800)和PP根治率(χ2 = 1.551、P = 0.297)差异均无统计学意义。研究组和对照组不良反应发生率分别为8.0%(4/45)和12%(6/50),差异无统计学意义(χ2 = 0.243、P = 0.744)。研究组中伴有萎缩性胃炎患者再次治疗后ITT根治率(96.77% vs. 75.85%)和PP根治率(96.77% vs. 78.57%)显著优于对照组中伴有萎缩性胃炎患者,差异有统计学意义(χ2 = 5.670、P = 0.017,χ2 = 4.662、P = 0.031)。单因素分析显示,不同药物依从性(服药率≥ 90%和< 90%)、患者ITT根治率(91.57% vs. 25.00%)和PP根治率(93.83% vs. 27.27%)差异均有统计学意义(χ2 = 28.59、P < 0.001,χ2 = 8.139、P = 0.004)。而不同年龄、性别、吸烟、饮酒、是否伴有萎缩性胃炎、是否伴有消化不良、合并糖尿病、合并高血压、DOB值、根治药物等的患者ITT根治率和PP根治率差异均无统计学意义(P均> 0.05)。多因素Logistic分析显示,药物依从性为幽门螺杆菌感染根除后复发根治疗效的影响因素(OR = 0.035、95%CI:0.007~0.199、P < 0.001)。

结论

以莫西沙星为基础的含铋四联疗法和以甲硝唑为基础的含铋四联疗法均可作为幽门螺杆菌感染复发患者治疗方案;两种方案的不良反应发生率相当。药物依从性为影响幽门螺杆菌感染复发根治疗效的独立影响因素。

Objective

To evaluate the efficacy, safety and influencing factors of two bismuth-containing quadruple therapies in the treatment of recurrent Helicobacter pylori (H. pylor) infection.

Metheds

Total of 95 patients with H. pylor recurrence infection from March 2017 to October 2020 in Tsinghua University Yuquan Hospital (Tsinghua University Hospital of Integrated Traditional Chinese and Western Medicine) were divided into experimental group (45 cases) and control group (50 cases) by ramdom envelope method, and there were 31 cases and 28 cases with atrophic gastritis in experimental group and control group, respectively. The experimental group were treated with colloidal bismuth pectin (200 mg, twice a day) + rabeprazole (10 mg, twice a day) + amoxicillin (1 000 mg, twice a day) + moxifloxacin (0.4 mg, once a day). The control group were treated with bismuth pectin (200 mg, twice a day) + rabeprazole (10 mg, twice a day) + amoxicillin (1 000 mg, twice a day) + metronidazole (0.4 mg, three times a day). All patients of the two groups were treated for 2 weeks. Then 13C urease breath test were performed on cases in both groups after 4-8 weeks. The eradication rate of recurrent H. pylor, eradication rate of cases with atrophic gastritis and the incidence of adverse drug reactions in 4 weeks after treatment were evaluated by Chi-square test. The risk factors for recurrent treatment failure of H. pylor were analyzed by Univariate and multivariate Logistic regression analysis.

Results

In experimental group, 45 cases completed the treatment after relapse, among them, 37 cases with H. pylor infection successfully eradicated, the eradication rates of intention-to-treat analysis (ITT) and per-protocol (PP) were 82.22% (37/45) and 94.87% (37/39), respectively. In control group, 50 cases completed the treatment after relapse, among them, 42 cases with H. pylor infection successfully eradicated, the eradication rates of ITT and PP were 82.22% (42/50) and 87.5% (42/48), respectively. There were no significant differences between the two groups for the eradication rates of ITT (χ2 = 0.783, P = 0.800) and PP (χ2 = 1.551, P = 0.297). The incidences of adverse reactions of experimental group and control group were 8.0% (4/45) and 12% (6/50), respectively, with no significant difference (χ2 = 0.243, P = 0.744). The eradication rates of ITT (96.77% vs. 75.85%) and PP (96.77% vs. 78.57%) after retreatment of patients complicated with atrophic gastritis in experimental group were significantly different from those of the control group (χ2 = 5.670, P = 0.017; χ2 = 4.662, P = 0.031). Univariate analysis showed that the eradication rates of ITT (91.57% vs. 25.00%) and PP (93.83% vs. 27.27%) between patients with different drug dependence (rate of taking medication ≥ 90% and < 90%) were significantly different (χ2 = 28.59, P < 0.001; χ2 = 8.138, P = 0.004). However, there was no significant difference for the eradication rates of ITT and PP between patients with different factors, such as age, sex, smoking, alcohol consumption, dyspepsia, dyspepsia, diabetes, hypertension, DOB value and radical drugs (all P > 0.05). Multivariate Logistic analysis showed that drug dependence was a factor influencing the recurrent curative efficacy after the eradication of H. pylori infection (OR = 0.035, 95%CI: 0.007-0.199, P < 0.001).

Conclusions

Both moxifloxacin based bismuth-containing quadruple therapy and metronidazole based bismuth-containing quadruple therapy could be used to treat patients with recurrent H. pylor infection; with similar incidence of adverse reactions. Drug compliance was an independent influencing factor for the efficacy of radical treatment for recurrence of H. pylor infection.

表1 两组患者的基线资料
表2 两组复发病例的根治率和药物依从性[例(%)]
表3 两组患者根治过程中不良反应发生率[例(%)]
表4 两组中伴有和不伴有萎缩性胃炎患者再次治疗后ITT和PP根治率(%)
表5 幽门螺杆菌感染根除后复发ITT和PP根治率的影响因素
影响因素 ITT根治率(%) χ2 P PP根治率(%) χ2 P
年龄(岁)   0.846 0.358b   1.590 0.207b
  > 45 85.92(61/71)     93.85(61/65)    
  < 45 75.00(18/24)     81.82(18/22)    
性别   2.005 0.157a   1.023 0.312b
  78.00(39/50)     86.67(39/45)    
  88.89(40/45)     95.24(40/42)    
吸烟   0.161 0.689b   0.000 1.000b
  78.26(18/23)     90.00(18/20)    
  84.72(61/72)     91.04(61/67)    
饮酒   0.794 0.373b   2.855 0.091b
  73.68(14/19)     77.78(14/18)    
  85.53(65/76)     94.20(65/69)    
伴有萎缩性胃炎   1.432 0.232a   0.728 0.393b
  86.67(52/60)     88.14(52/59)    
  77.14(27/35)     96.43(27/28)    
伴有消化不良   0.579 0.447b   0.000 1.000b
  85.33(64/75)     91.43(64/70)    
  75.00(15/20)     88.23(15/27)    
合并糖尿病   0.061 0.804b   0.182 0.670b
  76.92(10/13)     83.33(10/12)    
  84.15(69/82)     92.00(69/75)    
合并高血压   0.107 0.743b   0.000 1.000b
  77.78(14/18)     93.33(14/15)    
  84.42(65/77)     90.28(65/72)    
DOB值   1.894 0.449c   2.133 0.400c
  低负荷(5~15) 72.22(13/18)     81.25(13/16)    
  中负荷(16~35) 85.45(47/55)     92.16(47/51)    
  高负荷(≥ 36) 86.36(19/22)     95.00(19/20)    
根治药物   0.053 0.817a   0.657 0.418b
  莫西沙星组 82.22(37/45)     94.87(37/39)    
  甲硝唑组 84.00(42/50)     87.50(42/48)    
药物依从性   28.59 < 0.001b   8.138 0.004b
  服药率≥ 90% 91.57(76/83)     93.83(76/81)    
  服药率< 90% 25.00(3/12)     50.00(3/6)    
表6 幽门螺杆菌感染根除后复发ITT和PP根治率影响因素的多因素Logistic分析
[1]
Hu Y, Zhu Y, Lu NH, et al. Novel and effective therapeutic regimens for Helicobacter pylori in an era of increasing antibiotic resistance[R]. Front Cell Infect Microbiol,2017,7(168):1-20
[2]
赵靖涛,樊玲,张意. 幽门螺杆菌感染根除后复发及其影响因素的研究[J]. 胃肠病学2020,25(2):104-108.
[3]
谢琼,卢月月,易宏锋. 上消化道症状与幽门螺杆菌感染及胃癌前疾病的相关性[J/CD]. 中华实验和临床感染病杂志(电子版),2016,10(3):319-322.
[4]
Yang JC, Lu CW, Lin CJ. Treatment of Helicobacter pylori infection: current status and future concepts[J]. World J Gastroenterol, 2014,20(18):5283-5293.
[5]
Savoldi A, Carrara E, Graham DY, et al. Prevalence of antibiotic resistance in Helicobacter pylori: A systematic review and Meta-analysis in World Health Organization Regions[J]. Gastroenterology, 2018,155(5):1372-1382, e1317.
[6]
杜菲,董银凤,陈天辉. 幽门螺杆菌根治与复发研究进展[J]. 国际流行病学传染病学杂志,2020,47(2):169-173.
[7]
Fallone CA, Chiba N, van Zanten SV, et al. The toronto consensus for the treatment of Helicobacter pylori infection in adults[J]. Gastroerology,2016,151(1):51-69.
[8]
Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection--the Maastricht Ⅴ/Florence Consensus Report[J]. Gut,2012,61:646-664
[9]
Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis[J]. Gut,2015,64(9):1353-1367.
[10]
中华医学会消化病学分会幽门螺杆菌和消化性溃疡学组,全国幽门螺杆菌研究协作组. 第五次全国幽门螺杆菌感染处理共识报告[J]. 中华消化杂志,2017,37(6):364-378.
[11]
Yun J, Wu Z, Qi G, et al. The high-dose amoxicillin-proton pump inhibitor dual therapy in eradication of Helicobacter pylori infection[J]. Expert Rev Gastroenterol Hepatol,2021,15(2):149-157.
[12]
Kiyotoki S, Nishikawa J, Sakaida I, et al. Efficacy of vonoprazan for Helicobacter pylori eradication[J]. Intern Med,2020,59(2):153-161.
[13]
Niv Y, Hazazi R. Helicobacter pylori recurrence in developed and developing countries: Meta-analysis of 13C-urea breath test follow-up after eradication[J]. Helicobacter,2008,13(1):56-61.
[14]
Hu Y, Wan JH, Li XY, et al. Systematic review with meta-analysis: the global recurrence rate of Helicobacter pylori[J]. Aliment Pharmacol Ther,2017,46(9):773-779.
[15]
Zhao H, Yan P, Zhang N, et al. The recurrence rate of Helicobacter pylori in recent 10 years: A systematic review and meta-analysis[J]. Helicobacter,2021:00(e12852):1-9.
[16]
Flores-Trevino S, Mendoza-Olazaran S, Bocanegra-Ibarias P, et al. Helicobacter pylori drug resistance: therapy changes and challenges[J]. Expert Rev Gastroenterol Hepatol,2018,12(8):819-827.
[17]
Hwang JJ, Lee DH, Yoon H,et al. Efficacy of moxifloxacin-based sequential and hybrid therapy for first-line Helicobacter pylori eradication[J]. World J Gastroenterol,2015,21(35):10234-10241.
[18]
Sun Y, Zhang J. Helicobacter pylori recrudescence and its influencing factors[J]. J Cell Mol Med,2019,23(12):7919-7925.
[19]
Vale FF, Vadivelu J, Oleastro M, et al. Dormant phages of Helicobacter pylori reveal distinct populations in Europe[R]. Scientific Reports,2015,9(14333):1-8
[20]
Salipante SJ, Sen Gupta DJ, Cummings LA, et al. Application of whole-genome sequencing for bacterial strain typing in molecular epidemiology[J]. J Clin Microbiol,2015,53(4):1072-1079.
[21]
Ciccaglione AF, Cellini L, Grossi L, et al. Quadruple therapy with moxifloxacin and bismuth for first-line treatment of Helicobacter pylori[J]. World J Gastroenterol,2012,18(32):4386-4390.
[22]
Marusic M, Dominkovic L, Majstorovic Barac K, et al. Bismuth-based quadruple therapy modified with moxifloxacin for Helicobacter pylori eradication[J]. Minerva Gastroenterol Dietol,2017,63(2):80-84.
[23]
张丽颖,李保双,蔡毅东, 等. (13)C-尿素呼气试验定量值与胃黏膜病变程度的相关性[J]. 世界华人消化杂志,2013,21(2):177-181.
[24]
王海铭. 幽门螺杆菌胃内负荷, 不同毒力亚型与根除治疗的[D]. 吉林: 北华大学,2019:1-48.
[25]
李晓娟. 幽门螺杆菌根除效果影响因素分析[J]. 中华肿瘤防治杂志,2015,22(15):1165-1169.
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