| Background:The prevalence of antibiotic resistance for Helicobacter pylori(H.pylori)is increasing over the year,making it more difficult for traditional empirical therapy(ET)to successfully eradicate H.pylori.Thus,molecular-based antibiotic susceptibility testing(AST)has been frequently recommended to guide tailored therapy(TT).However,the efficacy of tailored therapy guided by molecular-based AST remains to be further confirmed.In addition,there is no clear reference standard for AST before eradication treatment.Objective:1.To evaluate the efficacy of empirical bismuth quadruple therapy for H.pylori infection in a certain area of Guangzhou,and to explore the risk factors of eradication failure.2.Meta-analyses were performed to explore and confirm the efficacy of tailored therapy guided by molecular-based AST.3.A nomogram model for predicting the risk of eradication failure was constructed and risk stratification was also performed to provide a reference for the timing of molecular-based AST before eradication therapy.Methods:1.Patients with H.pylori infection,who had received bismuth quadruple therapy in the outpatient service of a hospital in Guangzhou from April 2021 to September 2022,were retrospectively enrolled.The eradication rates of different regimens and subgroups were calculated and compared.Univariate and multivariate analysis was performed to identify risk factors for eradication failure.2.A systematic literature review was performed in several databases,and singlearm meta-analysis and meta-analysis comparing the efficacy of TT and ET were performed successively to evaluate the efficacy of TT guided by molecular-based AST.3.Based on the outpatients of the hospital,a predictive nomogram model was constructed based on the factors related to eradication failure.The receiver operating characteristic curve(ROC)and calibration plot were used to assess the discriminative and predictive ability of the model.Results:1.A total of 2220 treatments were performed in the 2163 patients included in the study,and the overall eradication rate for H.pylori infection was 81.2%.The overall eradication rate of primary treatment was 82.8%,with the empirical bismuth quadruple therapy containing amoxicillin plus minocycline achieving the highest eradication rate(91.2%).The overall eradication rate of rescue therapy was only 66.4%,among which the eradication rates of minocycline plus amoxicillin or clarithromycin(71%～80%)were higher than other regimens of antibiotics combination(below 70%).Multivariate regression analysis showed that males,previous treatment history,advanced age,clinical symptoms,and regimens of metronidazole plus clarithromycin/quinolone/minocycline were independent risk factors of eradication failure.2.A total of 35 studies from 31 literature(4626 patients)were included in the single-arm meta-analysis.Overall,the pooled eradication rate of TT was 86,9%(95%CI:84.6%-89.1%)in the intention-to-treat(ITT)analysis and 91.5%(95%CI:89.7%93.1%)in per-protocol(PP)analysis.For first-line treatment,the eradication rate of TT was 86.6%(ITT analysis)and 91.7%(PP analysis),and for rescue treatment,it was 85.1%(ITT analysis)and 88.2%(PP analysis).When tailored rescue therapy was based on the detection of resistance to at least 4 antibiotics,eradication rates reached 89.4%(ITT analysis)and 91.9%(PP analysis).For genotypically susceptive strains,the eradication rate of TT with the corresponding susceptive antibiotics was 93.1%(95%CI:91.1%-94.8%),among which the pooled eradication rate of tailored bismuth quadruple regimen was the highest(94.6%).Besides,the eradication rate of 7-day TT or tailored triple therapy for genotypically susceptive strains could both reach more than 93.0%.A total of 21 studies were included(6565 patients)in the meta-analysis comparing the efficacy of TT and ET.Overall,TT was superior to ET(RR=1.11;95%CI:1.051.18;I2=82.0%).On first-line treatments,TT showed its superiority over ET(17 studies,RR:1.10,95%CI:1.03-1.16;I2=82.3%).In subgroup analyses,the efficacy of TT was significantly better than that of empirical triple therapy(RR=1.24,95%CI:1.18-1.30),however,it was comparable to that of first-line empirical quadruple therapy(RR=1.01,95%CI:0.96-1.06).Nevertheless,tailored bismuth quadruple therapy as first-line treatment appeared to be superior to empirical bismuth quadruple therapy(RR=1.19,95%CI:1.08-1.30).For rescue therapy,there was insufficient evidence to compare the difference in efficacy between TT and ET,with only two eligible control studies from one literature.3.The predictive factors of the predictive nomogram included sex,times of treatment,age,clinical symptoms,and regimens of antibiotics.The area under the curve of ROC in the training set and validation set was 0.70 and 0.69,respectively.Besides,the calibration curve was fairly consistent with the ideal curve in the calibration plot.These confirmed that the predictive model had a fair ability for identification and prediction.In risk stratification,the score ≤95 indicated low risk,between 96 and 125 indicated medium risk,and≥126 indicated high risk.Conclusion:1.The overall eradication rate of empirical bismuth quadruple therapy in the single center of the hospital in Guangzhou is 81.2%.For first-line treatment,the regimen of amoxicillin plus minocycline is superior to other regimens.But the efficacy of all empirical rescue regimens was unacceptable.Male,previous treatment history,advanced age,clinical discomfort symptoms,and regimens containing metronidazole(except for the regimen of metronidazole plus amoxicillin)are independent risk factors for eradication failure.2.TT guided by molecular-based AST can improve the eradication efficacy of H.pylori to some extent.TT with a shorter duration or less drug(without bismuth)can also achieve good eradication efficacy.The effectiveness of TT can be improved by expanding the coverage of AST or by adding bismuth.3.The predictive nomogram model is easy to use and can well predict the risk of H.pylori eradication failure,which has a certain reference value in clinical decisionmaking on whether to carry out molecular-based AST. |
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