【作者】 王慧；

【导师】 杨晓云；

【作者基本信息】 山东大学 ， 内科学（消化系病）（专业学位）， 2025， 硕士

【摘要】 研究背景幽门螺杆菌(Helicobacter pylori,H.pylori)感染全球约50%的人口,且与多种消化系统疾病密切相关。然而随着抗生素耐药率的上升,H.pylori的根除仍是一项巨大的挑战。指南推荐铋剂四联方案(抑酸剂+铋剂+两种抗生素)作为H.pylori感染初次治疗和补救治疗的一线方案。在抗生素的选择中,阿莫西林因其耐药率低、不良反应少等多种因素,成为根除H.pylori的关键性抗生素。但在临床实践中,约有5-10%的患者对青霉素过敏,且有患者因其他原因无法应用阿莫西林,这些患者根除H.pylori的药物选择有限,面临更大的困难。因此需要进一步优化青霉素过敏H.pylori感染患者的治疗方案。研究目的本研究评估含头孢呋辛-四环素的铋剂四联方案相比于含头孢呋辛-左氧氟沙星的铋剂四联方案作为青霉素过敏H.pylori感染患者一线治疗方案的有效性和安全性。研究方法本研究是一项多中心、开放标签、非劣效性随机对照研究。研究对象为对青霉素过敏的未经治疗的H.pylori感染患者。受试者被随机分配到14天Cef-Tet BQT组(替戈拉生50 mg bid、枸橼酸铋钾220 mg bid、头孢呋辛500 mg bid、四环素500 mg tid)和14天Cef-Lev BQT组(替戈拉生50 mg bid、枸橼酸铋钾220 mg bid、头孢呋辛500 mg bid、左氧氟沙星500 mg qd)。主要研究结果是评估Cef-Tet BQT 组和 Cef-Lev BQT组H.pylori的根除率,次要研究结果是评估两组治疗方案的不良反应发生率和患者依从性。研究结果本研究共纳入248名受试者。在意向性分析中,Cef-Tet BQT组的根除率为90.32%[112/124,95%置信区间(Confidence Interval,CI):85.12%-95.52%],Cef-Lev BQT 组的根除率为 81.45%(101/124,95%CI:74.61%-88.29%)(P=0.045)。在改良意向性分析中,两组方案的根除率分别为91.80%(112/122,95%CI:86.93%-96.67%)和83.47%(101/121,95%CI:76.85%-90.09%)(P=0.048)。在符合方案分析中,两种方案的根除率分别为 92.37%(109/118,95%CI:87.58%-97.16%)和 85.34%(99/116,95%CI:78.90%-91.78%)(P=0.087)。在 ITT、MITT、PP 分析中,Cef-Tet BQT组H.pylori根除率均不劣于Cef-Lev BQT组(P<0.0001)。两组不良反应发生率(21.77%vs.24.19%)(P=0.651)和依从性(96.77%vs.95.97%)(P>0.999)差异无统计学意义。单因素回归分析显示:吸烟(P=0.033)、饮酒(P=0.057)、依从性差(P=0.008)、Cef-Lev BQT方案(P=0.053)是影响H.pylori根除疗效的潜在因素;进一步多因素回归分析中,依从性差(OR=6.68,95%CI:1.58-28.25,P=0.010)和 Cef-Lev BQT 方案(OR=2.38,95%CI:1.03-5.49,P=0.042)会增加H.pylori治疗失败的风险。研究结论对于青霉素过敏的H.pylori感染患者,含头孢呋辛-四环素的铋剂四联方案是有效且安全的一线治疗方案。更多还原

【Abstract】 BackgroundHelicobacter pylori(H.pylori)infected approximately 50%of the global population and is closely associated with various digestive system diseases.However,with the rising antibiotic resistance,the eradication of H.pylori remains a significant challenge.Guidelines recommend the use of bismuth quadruple therapy(acid suppressant+bismuth+two antibiotics)as the first-line regimen for the initial and rescue treatment of H.pylori infection.Among the antibiotics,amoxicillin is a key antibiotic for eradicating H.pylori due to various factors such as low resistance rate and fewer adverse effects.However,in clinical practice,about 5-10%of patients are allergic to penicillin,and there are also patients who cannot use amoxicillin for other reasons.These patients face greater difficulties in the eradication of H.pylori because of the limited drug options.Therefore,it is necessary to further optimize the treatment regimen for penicillin-allergic patients with H.pylori infection.AimsThis study evaluates the efficacy and safety of the Cefuroxime-Tetracycline-containing bismuth quadruple therapy(Cef-Tet BQT)compared to Cefuroxime-Levofloxacin-containing bismuth quadruple therapy(Cef-Lev BQT)as first-line treatment for H.pylori infection in penicillin-allergic patients.MethodsThis study was a multicenter,open-label,non-inferiority,randomized controlled trail.The study population were treatment-na(?)ve,penicillin-allergic patients with H.pylori infection.Participants were randomly assigned to the 14-day Cef-Tet BQT group(Tegoprazan 50 mg twice daily,bismuth potassium citrate 220 mg twice daily,cefuroxime 500 mg twice daily,tetracycline 500 mg three times daily)and the 14-day Cef-Lev BQT group(Tegoprazan 50 mg twice daily,bismuth potassium citrate 220 mg twice daily,cefuroxime 500 mg twice daily,levofloxacin 500 mg once daily).The primary study outcome was to assess the eradication rate of H.pylori in the Cef-Tet BQT group and the Cef-Lev BQT group.The secondary outcomes included the incidence of adverse events and patient compliance to the treatment regimens in both groups.ResultsA total of 248 patients were included in this study.The intention-to-treat(ITT)eradication rates were 90.32%[112/124,95%Confidence Interval(CI):85.12%-95.52%]for the Cef-Tet BQT group and 81.45%(101/124,95%CI:74.61%-88.29%)for the Cef-Lev BQT group(P=0.045).In the modified intention-to-treat(MITT)analysis,the eradication rates of the two groups were 91.80%(112/122,95%CI:86.93%-96.67%)and 83.47%(101/121,95%CI:76.85%-90.09%)(P=0.048),respectively.The per-protocol(PP)eradication rates were 92.37%(109/118,95%CI:87.58%-97.16%)and 85.34%(99/116,95%CI:78.90%-91.78%)(P=0.087),respectively.In the ITT,MITT，and PP analyses,the H.pylori eradication rate in the Cef-Tet BQT group was non-inferior to that in the Cef-Lev BQT group(P<0.0001).There was no statistically significant difference in the incidence of adverse events(21.77%vs.24.19%)(P=0.651)and compliance(96.77%vs.95.97%)(P>0.999)between the two groups.Univariate regression analysis showed that smoking(P=0.033),drinking(P=0.057),poor compliance(P=0.008)and Cef-Lev BQT regimen(P=0.053)were potential factors influencing the efficacy of H.pylori eradication.Further multivariate regression analysis indicated that poor compliance(OR=6.68,95%CI:1.58-28.25,P=0.010)and Cef-Lev BQT regimen(OR=2.38,95%CI:1.03-5.49,P=0.042)increased the risk of H.pylori treatment failure.ConclusionsBQT containing cefuroxime and tetracycline is an effective and safe first-line treatment option for penicillin-allergic patients with H.pylori infection.更多还原