Efficacy Of Half-dose Clarithromycin-containing Bismuth Quadruple Therapy In Helicobacter Pylori Eradication

Background:Helicobacter pylori(H.pylori)is a spiral shaped and microaerobic Gram-negative bacilli.Nowadays,over 50%of the world population is infected with H.pylori.Persistent infection with H.pylori may associated with chronic gastritis,peptic ulcer disease,gastric cancer and MALT lymphoma.Eradication of this organism has been shown to accelerate ulcer healing,reduce the risk of gastric cancer.The choice of eradication regimen is an important and difficult point in the treatment of H.pylori infection.The ultimate goal remains to find a safe,tolerable,cheap,and highly effective regimen.Clarithromycin resistance rates have now reached-50%in China.Bismuth quadruple therapy is the recommended first-line treatment in areas with high clarithromycin resistance rates.The costs of treatment and the occurrence of antibiotic-related adverse effects may affect the compliance of patient,thereby reducing the eradication rates.It may adds to the growing problem of antibiotic resistance.Clarithromycin has been widely used in the eradication of H.pylori.Therefor,it is necessary to explore whether it can achieve satisfactory rates of eradication and reduce the adverse effects when we use half-dose clarithromycin in the treatment of H.pylori.Cytochrome P450(CYP)isozymes(mainly CYP2C19 and CYP3A4)play an important role in the metabolism of PPIs in humans.Polymorphisms in CYP2C19 are associated with 3 genotypes:extensive metabolism(EM),intermediate metabolism(IM),and poor metabolism(PM).Polymorphisms in CYP2C19 have been reported to affect its activity in the liver and,thus,the metabolic and pharmacokinetic profiles of PPIs.Therefor,the clinical efficacy of PPI-based therapy for the eradication of H.pylori may be affected by CYP2C19 genotype.Objectives:The aim of our study was to evaluate the efficacy and tolerability of 14-day half-dose clarithromycin-containing bismuth quadruple therapy for the eradication of H.pylori.It also investigate whether CYP2C19 genotype status affected the H.pylori eradication rates with the esomeprazole-based bismuth quadruple therapy.Method:A total of 202 consecutive patients infected with H.pylori were enrolled in this trial.Group A(half-dose group)received esomeprazole(20mg),amoxicillin(lg),clarithromycin(250mg)and bismuth potassium citrate(0.6g),all twice daily for 14 days.Group B(standard-dose group)received esomeprazole(20mg),amoxicillin(lg),clarithromycin(500mg)and bismuth potassium citrate(0.6g),all twice daily for 14 days.C13-urea breath test were performed 4-8 weeks after treatment.The primary outcome was H.pylori eradication rates by intention-to-treat(ITT)and per-protocol(PP)analysis.Compliance and side effects were evaluated throughout the period in a medicine.When we analyzed the cost-effectiveness using the cost-effectiveness ratio and incremental cost-effectiveness ratio.We defined cost as direct medical costs and effectiveness as PP eradication rates.Blood samples(2ml)were collected into heparinized tubes.DNA was extracted from the peripheral whole blood.CYP2C19 genotype was determined by the PCR-allele specific oligonucleotide method.Results:A total of 202 patients were enrolled in this study,including 111 patients with half-dose clarithromycin and 91 patients with standard-dose clarithromycin.There was no significant difference in age,sex,BMI and smoking status between the two groups.The eradication rates of the half-dose and standard-dose groups were 91.0%(101/111)and 89.0%(81/91)respectively,according to ITT analysis(P=0.64).PP eradication rates were 96.2%(101/105)and 96.4%(81/84)respectively(P=1.00).The number of patients reporting any adverse effect was higher in the standard-dose group(20.0%vs.33.3%;P=0.04).The compliance of the half-dose and standard-dose groups were 100%(105/105)and 95.3%(84/87)respectively(p=0.09).The direct medical costs per patient is 611.97 yuan in half-dose group and 847.73 yuan in standard-dose group.The cost-effectiveness ratio is 6.36 in half-dose group and 8.79 in standard-dose group.The incremental cost-effectiveness ratio is 1178.8.In the 116patients included in PP analysis of the effect of CYP2C19 genotype,eradication rates were 96.0%(48/50)in EM metabolism group,95.4%(62/65)in IM+PM metabolism group.Eradication rates did not differ significantly among phenotype groups(p=1.00).Conclusion:A 14-day half-dose clarithromycin-containing quadruple regimen is equally effective but better tolerated than its standard-dose regimen in the treatment of helicobacter pylori.CYP2C19 genotype status did not affect the rates of H.pylori eradication with the esomeprazole-containing bismuth quadruple regimen.