Low efficacy rate of moxifloxacin-containing Helicobacter pylori eradication treatment: in an observational study in a Turkish population

BACKGROUND: Standard triple therapy for Helicobacter pylori has an eradication rate of about 50% in Turkey. It may be due to an increased resistance of H. pylori to antibiotics. Therefore, we aimed to investigate the effectiveness of a new second-generation fluoroquinolone, moxifloxacin-containing triple therapy in H. pylori eradication. MATERIAL AND METHODS: This is an open-label, prospective, single-center, pilot study. We studied 71 dyspeptic patients infected with H. pylori diagnosed by both histology and rapid urease test. Out of 71 dyspeptic patients, 64 had non-ulcer dyspepsia and seven had peptic ulcer. Patients received pantoprazole (40 mg b.i.d.) plus moxifloxacin (400 mg/day) and amoxicillin (1000 mg b.i.d.) for 14 days. Eradication was assessed 4 weeks after completing the therapy by histology and rapid urease test. Per-protocol and intention-to-treat eradication rates were determined. RESULTS: The eradication rate was 42.2% for the intention-to-treat analysis and 47.6% for the per-protocol analysis. Of all patients included in the study, 29.5% had side-effects and only 2.8% of the patients discontinued the treatment because of side-effects. Most of the complications were mild and self-limiting. CONCLUSION: Triple therapy with pantoprazole, moxifloxacin, and amoxicillin for 14 days yielded unacceptably low eradication rates. However, using tests of susceptibility to antibiotics, further studies with larger sample sizes are needed to judge these eradication rates of moxifloxacin containing eradication treatment.     

In Search of the Holy Grail of Heliocobacter pylori Remedies

In this issue, Gisbert et al. (pp. 157–62) present the results of a noncomparative study evaluating a twice daily, 5‐day regimen of ranitidine bismuth citrate, amoxicillin, clarithromycin and metronidazole twice daily for Helicobacter pylori cure. This study is one of a few stuides that evaluate a 5‐day triple antimicrobial regimen in combination with a antisecretory agent. Although the study design precludes making any definite conclusion, it does encourage additional investigation of these types of regimens. Randomized controlled trials (RCTs) using regimens containing multiple agents should consider both standard‐of‐care comparator regimens and comparator regimens that will provide a better understanding of why regimens are more effective or better tolerated. The goal of treatment should be to maintain a lower bound 95% confidence interval (CI) of the point estimate of greater than 80% and a ‘delta’ (lower bound 95% CI of the difference in rates) of less than 10%. All RCTs should conduct susceptibility testing to evaluate the impact of resistance on efficacy and explain eradication failures. Finally, consideration should be given to the inclusion of patients with functional dyspepsia in H. pylori studies evaluating H. pylori cure since patients with peptic ulcer disease are becoming harder to find.     

Annual Change of Primary Resistance to Clarithromycin among Helicobacter pylori Isolates from 1996 through 2008 in Japan

Background: Recent studies have shown that the combination of proton pump inhibitor, amoxicillin and clarithromycin is one of the best choices for Helicobacter pylori eradication therapy. However, increasing number of cases of H. pylori infection showing resistance to clarithromycin therapy has been reported and this is currently the main cause of eradication failure. We investigated the annual changes of the antimicrobial susceptibility to clarithromycin, amoxicillin and minocycline during a period of 12 years in Japan. Methods: This study comprised 3521 patients (mean age (SD), 55.4 (13.7) years‐old, 2467 males and 1054 females) positive for H. pylori as assessed by microaerobic bacterial culture from 1996 through 2008. All patients were previously untreated for H. pylori and were enrolled in the study to assess primary resistance to the three antibiotics. Results: The overall primary resistance to clarithromycin, amoxicillin and minocycline were 16.4%, (577/3521), 0.03% (1/3521) and 0.06% (2/3521), respectively. From1996 through 2004, the resistance rate to clarithromycin increased gradually to approximately 30% and then it remained without marked fluctuation since 2004. Analysis by gender showed a significant increase (p < .0001) in resistance rate to clarithromycin among females (217/1057, 20.6%) compared to males (360/2467, 14.6%). Analysis by age, disclosed significantly (p < .0001) higher resistance rate to clarithromycin in patients of more than 65‐years‐old compared to the younger population. Conclusions: The resistance rate of H. pylori infection to clarithromycin in Japan has increased gradually to approximately 30% from 1996 through 2004, and remained unchanged since 2004. Elderly and females were at high risk of having resistance to clarithromycin. Our results suggested that the level of clarithromycin resistance in Japan has now risen to the point where it should no longer be used as empiric therapy.     

Comparison of 7-day and 14-day proton pump inhibitor-containing triple therapy for Helicobacter pylori eradication: neither treatment duration provides acceptable eradication rate in Korea

BACKGROUND AND AIMS: Although triple combination therapy containing a proton pump inhibitor (PPI) and two antibiotics is considered as a standard regimen for the first-line anti-Helicobacter pylori treatment, there are still debates on the ideal duration of treatment. The aim of this study was to compare the efficacies of 7-day and 14-day PPI-containing triple therapy. MATERIALS AND METHODS: This study was performed in a randomized, multicenter, prospective manner. After upper gastrointestinal endoscopy, H. pylori-infected patients with a gastric ulcer and/or a duodenal ulcer were randomly assigned to a PAC7 group (omeprazole 20 mg or equivalent dose of other PPIs, amoxicillin 1000 mg, and clarithromycin 500 mg twice daily for 7 days) or to a PAC14 group (the same regimen as the PAC7 group but for 14 days). H. pylori status was evaluated by (13)C urea breath test 5 weeks after anti-ulcer treatment completion. RESULTS: A total of 598 patients were enrolled; 337 were randomized to the PAC7 group and 261 to the PAC14 group. The two groups were comparable in terms of baseline characteristics. The eradication rates of the PAC7 group were not inferior to those of the PAC14 group in both intention-to-treat analysis (71.2% vs. 75.5%) and per-protocol analysis (83.6% vs. 86.6%). Incidences of adverse events were comparable. CONCLUSIONS: Although the 7-day PPI-containing triple anti-H. pylori therapy is not inferior to the 14-day therapy, neither treatment duration provides acceptable eradication rate reaching 90% in per-protocol analysis. New combination regimen with higher efficacy should be developed as a first-line eradication therapy for H. pylori in Korea.     

Antibacterial effects of the urushiol component in the sap of the lacquer tree (Rhus verniciflua Stokes) on Helicobacter pylori

Background: Urushiol is a major component of the lacquer tree which has been used as a folk remedy for the relief of abdominal discomfort in Korea. The aim of this study was to evaluate the antibacterial effects of the urushiol on Helicobacter pylori. Materials and Methods: Monomer and 2–4 polymer urushiol were used. In the in vitro study, pH‐ and concentration‐dependent antibacterial activity of the urushiol against H. pylori were investigated. In addition, the serial morphological effects of urushiol on H. pylori were examined by electron microscopy. In vivo animal study was performed for the safety, eradication rate, and the effect on gastritis of urushiol. The expression of pro‐inflammatory cytokines was checked. Results: All strains survived within a pH 6.0–9.0. The minimal inhibitory concentrations of the extract against strains ranged 0.064–0.256 mg/mL. Urushiol caused separation of the membrane and lysis of H. pylori within 10 minutes. Urushiol (0.128 mg/mL × 7 days) did not cause complications on mice. The eradication rates were 33% in the urushiol monotherapy, 75% in the triple therapy (omeprazole + clarithromycin + metronidazole), and 100% in the urushiol + triple therapy, respectively. H. pylori‐induced gastritis was not changed by urushiol but reduced by eradication. Only the expression of interleukin‐1β in the gastric tissue was significantly increased by H. pylori infection and reduced by the urushiol and H. pylori eradication (p = .014). Conclusions: The urushiol has an antibacterial effect against H. pylori infection and can be used safely for H. pylori eradication in a mouse model.     

Bismuth-Containing Quadruple Therapy as Second-Line Treatment for Helicobacter pylori Infection: Effect of Treatment Duration and Antibiotic Resistance on the Eradication Rate in Korea

Background:  The eradication rate of first-line Helicobacter pylori treatment is only 70–85% and has been decreasing due to the increase in antibiotic resistance. The aim of this study was to evaluate the efficacy of bismuth-containing quadruple therapy as second-line treatment for H. pylori infection based on treatment duration.
Methods:  We prospectively enrolled 227 patients that were found to have persistent H. pylori infection after first-line proton-pump inhibitor-clarithromycin-amoxicillin triple therapy. Patients were randomized to 1-week (112 patients) and 2-week (115 patients) quadruple therapy with tripotassium dicitrate bismuthate 300 mg q.i.d., meteronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. and esomeprazole 20 mg b.i.d. The eradication rate, drug compliance, and adverse events were compared based on treatment duration.
Results:  The eradication rates were 72/112 (64.3%, 95% CI: 0.504–0.830) and 71/92 (77.2%, 0.440–0.749) with 1-week group, and 95/115 (82.6%, 1.165–2.449) an 88/94 (93.6%, 1.213–5.113) with 2-week group by intention-to-treat therapy ( p  = .002) and per-protocol analysis ( p  = .001), respectively. The adverse events increased as the treatment durations increased from 7 to 14 days (20.0 and 42.5%, respectively, p  < .001). However, there was no significant difference in the patient compliance or the rate of major adverse events between the 1- and 2-week groups (6.3 and 12.5%, respectively, p  = .133).
Conclusion:  Two-week bismuth-containing quadruple therapy was more effective than the 1-week treatment, and should be considered for second-line treatment in Korea.