| BackgroundApproximately 4.4 billion individuals were affected by Helicobacter pylori,which was closely associated with 90% of non-cardia gastric cancers and 86% of non-Hodgkin lymphoma of gastric location(mucosa associated lymphoid tissue lymphoma and diffuse large B cell lymphoma).The eradication of Helicobacter pylori was a viable strategy to prevent gastric cancer,and approximately 80% of patients with early gastric mucosa associated lymphoid tissue lymphoma can be relieved by eradicating Helicobacter pylori.Standard triple therapy(proton pump inhibitor,amoxicillin,clarithromycin or metronidazole)was recommended as the first-line eradication therapy.Unfortunately,with the growing resistance to clarithromycin and metronidazole,the efficacy of standard triple therapy has fallen below 80%.Therefore,bismuth quadruple therapy and non-bismuth quadruple therapy were recommended as alternative regimens.Although these regimens could achieve acceptable eradication rates,the complexity and high adverse events of multi-drug regimens may reduce the patient compliance.However,both the primary and second resistance to amoxicillin was in low level in most regions.Proton pump inhibitor and amoxicillin dual therapy was introduced to eradicate H.pylori infection in the late 1980 s.However,the efficacy of this dual therapy with twice-daily dosing was just unacceptable,and the unsustainable inhibition of intragastric acid excretion and bactericidal effect of amoxicillin might be possible reasons.Several studies have reported that high dose dual therapy(PPI and amoxicillin both given four times daily for 14 days)achieved an eradication rate of more than 85%.But the complexity of this high dose dual therapy might impair patient compliance,and the double-dose drug consumption would increase the incidence of drug-induced adverse events and financial burden to families and societies.It is still unclear whether modified high dose dual therapy with a shortened treatment course or reduced dosing frequency could be an effective treatment against H.pylori.Based on assessing the effectiveness and safety of PPI-amoxicillin high dose dual therapy for treatment of Helicobacter pylori infection in comparison to other regimens,and local Helicobacter pylori resistance patterns,we conducted an open-label,randomized control trial to compare the efficacy and safety of two modified regimens of esomeprazole-amoxicillin dual therapy in patients with Helicobacter pylori infection.Method1.Searching PubMed,Embase,and the Cochrane Register of Controlled Trials to find relevant articles.Randomized controlled trials using the intervention of high dose proton pump inhibitor-amoxicillin dual therapy for adult patients with Helicobacter pylori infection were included.The primary outcome was eradication rate by intention-to-treat analysis and adverse events were primary and second outcome,respectively.2.The agar dilution method was used to evaluate antibiotic resistance of Helicobacter pylori,which were isolated from gastric biopsies of patients inspected at Daping Hospital from January 2015 to December 2017.Statistical analysis was performed to investigate the local Helicobacter pylori resistance patterns.3.In this trial,we recruited 208 patients with Helicobacter pylori infection.They were randomly allocated to 10-day modified dual therapy group(esomeprazole 20 mg and amoxicillin 750 mg,four times daily)or 14-day modified dual therapy group(esomeprazole 20 mg and amoxicillin 750 mg,three times daily).Result1.Eleven trials were eligible for analysis.High dose proton pump inhibitor-amoxicillin dual therapy was as effective as the recommended regimens(p = 0.64),with fewer adverse events(p < 0.0001).2.We successfully cultured 3841 Helicobacter pylori strains(25.81%)from 14882 gastric biopsies.The strains from the male were significantly more than those from the female(P<0.05).The resistance rate to metronidazole was 94.09%,clarithromycin 26.30%,levofloxacin 33.98%,amoxicillin 0.26%,furazolidone 0%,and tetracycline 0%.During the past three years,the antibiotic resistance rates to metronidazole,clarithromycin and levofloxacin increased from 88.97%,22.41% and 21.72% to 96.88%,25.87% and 36.83%(P<0.05).Strains from the female were more likely to be resistant to clarithromycin and levofloxacin.A remarkable rise of resistance to metronidazole and levofloxacin were observed with growth of age.3.In this clinical trial,there was no significant difference of efficacy between 10-day modified dual therapy and 14-day modified dual therapy in intention-to-treat analysis(79.8% versus 82.7%,p = 0.594)or per-protocol analysis(81.2% versus 85.1%,p = 0.690).both the two regimens were well tolerated,with few adverse events(5.9% in 10-day group and 4.9% in 14-day group).Patient compliance(OR 24.7,95% CI 2.8-218.2,p = 0.004)and smoking(OR 0.4,95% CI 0.2-0.8,p = 0.017)were independent risk fators in the multiple logistic regression analysis.ConclusionHigh dose proton pump inhibitor-amoxicillin dual therapy was as effective as recommended regimens for treatment naive or experienced patients with fewer adverse effects.High dose proton pump inhibitor-amoxicillin dual therapy has potential to be first-line or rescue treatment for Helicobacter pylori infection.The prevalence of Helicobacter pylori resistance to clarithromycin,metronidazole and levofloxacin in Chongqing reached an alarming level.But the resistance to amoxicillin,furazolidone or tetracycline still remained rare.These antibiotics could be used for Helicobacter pylori infection,irrespective the prevalence of antibiotic resistance.According to the results of the randomized control trial,14-day modified dual therapy tends to be more effective than 10-day modified dual therapy,achieving a borderline acceptable efficacy for H.pylori infection.Poor adherence and smoking could impair the treatment efficacy.Taken together,14-day modified proton pump inhibitor-amoxicillin dual therapy could be an effective and well-tolerated regimen for people with Helicobacter pylori infection in Chongqing. |
PDF Full Text Request