Background:Increasing Helicobacter pylori resistance has led to decreases in treatment effectiveness.Aim: To test the effectiveness of susceptibility-guided therapy vs a locally highly effective empiric modified bismuth quadruple therapy for first-line H pylori treatment in a region with high antimicrobial resistance. Methods:We compared 14-day susceptibility-guided with empiric therapy using a multicentre superiority-design trial, which randomised H pylori infected subjects 3:1 to (a) susceptibility-guided therapies contained esomeprazole 20 mg and amoxicillin 1 g b.d. plus clarithromycin 500 mg, metronidazole 400 mg b.d., or levofloxacin 500 mg daily for susceptible infections or bismuth 220 mg b.d. and metronidazole 400 mg q.d.s. for triple-resistant infections; (b) Empiric therapy contained esomeprazole 20 mg, bismuth 220 mg b.d., amoxicillin 1 g and metronidazole 400 mg t.d.s.Primary outcome was H pylori eradication. Results: Between February 2017 and March 2018, 491 subjects were screened and 382 were randomised. Both the susceptibility-guided and the empiric regimens were highly successful with per-protocol eradication rates of 97.7% (250/256) vs 97.6% (81/83, P = 1.00) and intent-to-treat eradication rates of 91.6% (262/286) vs 85.4%(82/96, P = 0.12). Overall, susceptibility-guided therapy was not superior to empiric therapy with 0.1% per-protocol (95% CI −3.1% to 3.2%) and 6.2% intent-to-treat (−0.3% to 12.7%) eradication difference. Both approaches had high adherence and low adverse event rates.Conclusions: Both susceptibility-guided and empiric therapies provided excellent eradication rates. Clinically, the choice would hinge on availability of susceptibility testing and/or a locally highly effective empiric therapy. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information will be found online in the Supporting Information section at the end of the article.How to cite this article: Chen Q, Long X, Ji Y, et al.Randomised controlled trial: susceptibility-guided therapy versus empiric bismuth quadruple therapy for first-line Helicobacter pylori treatment. Aliment Pharmacol Ther.

ObjectiveThe purpose of this study was to evaluate the efficacy of high dose of metronidazole in the treatment of Helicobacter pylori (H. pylori) infection.MethodsStudies were identified from databases (Pubmed, Embase, Cochrane Library, ClinicalTrials.gov) searched from January 1990 to September 2017 using a battery of keywords. We included randomized controlled trials (RCTs) of H. pylori treatment comparing the high-dose and low-dose metronidazole-containing therapies (high-dose and low-dose therapies). Two reviewers independently selected studies, extracted relevant data and assessed study quality. A meta-analysis was performed by using Review Manager 5.3. Dichotomous data were pooled to obtain the relative risk (RR) of the eradication rate, with 95% confidence intervals (CIs).ResultsFour randomized controlled trials, a total of 612 patients with a diagnosis of H. pylori infection were included. Overall the meta-analysis showed that both high-dose and low-dose therapies achieved similar efficacy of intention-to-treat (ITT) eradication rate 82% vs. 76%, RR 1.12 (95%CI: 0.96 to 1.30), P = 0.15, and adherence 94% vs. 94%, RR 1.00 (95%CI: 0.97 to 1.04), P = 0.81, but side effects were more likely in high-dose therapies [32% vs. 17%, RR 1.84 (95%CI: 1.17 to 2.88), P = 0.008]. In subgroup analysis, increasing the dose of metronidazole enhanced eradication rates in areas with high metronidazole resistance [74% vs 52%, RR 1.40 (95%CI: 1.08 to 1.82), P = 0.01] and in individuals with metronidazole-resistant strains [71% vs. 46%, RR 1.50 (95%CI: 1.02 to 2.19), P = 0.04].ConclusionsBoth high-dose and low-dose therapies can achieve similar eradication rates and adherence and generally low-dose therapies cause fewer side effects. In populations with high metronidazole resistance, high dose of metronidazole can increase the eradication rates of H. pylori infection.

BackgroundHelicobacter pylori (H pylori) treatment remains a challenge for penicillin‐allergic patients.AimTo evaluate the efficacy and tolerability of susceptibility‐guided first‐line and rescue treatment in H pylori‐infected penicillin‐allergic patients.MethodsConsecutive H pylori‐infected patients with penicillin allergy received a 14‐day triple or quadruple therapy based on susceptibility to clarithromycin, levofloxacin, and metronidazole. All received esomeprazole 20 mg twice a day. Metronidazole‐susceptible infections received metronidazole plus clarithromycin or levofloxacin triple therapy if susceptible. Clarithromycin‐ and levofloxacin‐resistant infections received metronidazole plus tetracycline triple therapy. Metronidazole‐resistant infections received a bismuth—high‐dose metronidazole plus clarithromycin or levofloxacin quadruple therapy. Triple‐resistant infections received classical bismuth quadruple therapy with high‐dose metronidazole. Antimicrobial susceptibility was assessed using the E test method.Results112 patients were entered (34.8% men, average 47.1 years). Infections in 83.8% (31/37) of treatment‐naive subjects and 12.0% (9/75) (P < .001) receiving rescue treatment were susceptible to at least one of the three tested antibiotics. Overall, susceptibility‐guided therapy achieved eradication rates of 92.9% (104/112, 95% CI 88.1%‐97.7%) by intent‐to‐treat analysis and 99% (100/101, 95% CI 97.1%‐100%) by per‐protocol analysis. All regimens achieved eradication rates greater than 90% (P = .327) in the PP populations. Adverse events were relatively frequent; however, compliance remained high.ConclusionSusceptibility‐guided therapy proved highly effective for penicillin‐allergic patients. When available and proven locally effective, the alternative was empiric classical bismuth quadruple therapy. This trial is registered with ClinicalTrials.gov as NCT03708848.

Words count of abstract: 249 15 Words count of text: 3806 16 17 2 Abstracts 18Backgrounds: There have been reports of Helicobacter pylori (H. pylori) in the oral cavity and it has 19 been suggested that the oral cavity may be a reservoir for H. pylori reflux from the stomach. 20Objectives: High-throughput pyrosequencing was used to assess the structure and composition of oral 21 microbiota communities in individuals with or without confirmed H. pylori infection. 22 Methods: Saliva samples were obtained from 34 H. pylori infected and 24 H. pylori uninfected 23 subjects. Bacterial genomic DNA was extracted and examined by pyrosequencing by amplification of 24 the 16S rDNA V3-V4 hypervariable regions followed by bioinformatics analysis. Saliva sampling was 25 repeated from 22 of the 34 H. pylori infected subjects 2 months after H. pylori eradication. 26 Results: High-quality sequences (2,812,659) clustered into 95,812 operational taxonomic units (OTUs; 27 97% identity), representing 440 independent species belonging to 138 genera, 68 families, 36 orders, 28 21 classes, and 11 phyla. Species richness (alpha diversity) of H. pylori infected subjects was similar to 29 that of uninfected subjects. Eradication treatment decreased saliva bacterial diversity. Beta diversity 30analysis showed that the salivary microbial community structure differed between H. pylori infected 31 and uninfected subjects both before and after H. pylori eradication. 32Conclusions: Salivary microbiota diversity was similar in H. pylori infected and uninfected individuals. 33Antibiotic therapy was associated with a decline in salivary bacterial diversity. Both H. pylori infection 34 and its eradication caused the oral microbiota alterations in community and structure. The present of H. Importance 39The oral cavity plays a vital role in Helicobacter pylori transmission among human. 40High-throughput pyrosequencing of the 16S rDNA V3-V4 hypervariable regions was used to assess the 41 structure and composition of oral microbiota communities in individuals with or without confirmed 42 Helicobacter pylori infection. We show that both Helicobacter pylori infection and eradication cause 43 microbiota alterations in the oral microbiota. Prior studies report detection of Helicobacter pylori in the 44 oral cavity by polymerase chain reaction. We show that the presence of Helicobacter pylori in the oral 45 cavity is unrelated with its infection status in the stomach. 46 47 4 48 Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human gastric 49 epithelium. It belonged to Helicobacter genus, Helicobacteraceae family, Campylobacterales order, 50 Epsilonproteobacteria class, and Proteobacteria phyla. H. pylori infection is characterized by mucosal 51 inflammation (gastritis) and may result in peptic ulcer disease or gastric adenocarcinoma (1). H. pylori 52 is transmitted between humans by a variety of routes including gastro-oral and fecal-oral mechanisms 53 that include contaminated water and food. It has also been postulated t...