Interaction of Drugs for Eradication Therapy against Antibiotic-Resistant Strains of Helicobacter pylori

To clarify the interactions of drugs for combination therapy of Helicobacter pylori infection, especially due to antibiotic-resistant strains, we have evaluated the in vitro effect of combining different drugs. Using a modified time-kill assay, we tested the effect of combining 2 drugs from 4 agents; amoxicillin (AMPC), clarithromycin (CAM), metronidazole (MTZ) and lansoprazole (a proton pump inhibitor). The H. pylori in the study consisted of 4 strains sensitive to the all drugs, 2 strains resistant only to CAM, 2 strains resistant only to MTZ, and 2 strains resistant to both CAM and MTZ. From the 6 different drug combinations, synergism was observed for 5 of the combinations, among which the combination of AMPC and CAM revealed such effects most frequently. However, all of the strains which showed synergism were sensitive to both of the drugs. In the case of the strains resistant to CAM and/or MTZ, no synergism was demonstrated in any of the combinations including CAM and/or MTZ. When a strain was resistant to one drug from a combination, no synergism was detected. Thus, the administration of a drug to which the strains are resistant may have no advantage in the eradication therapy of H. pylori. For a more effective and safer therapy, susceptibility testing should be performed before treatment.     

Helicobacter pylori Eradication Therapy May Facilitate Gastric Ulcer Healing After Endoscopic Mucosal Resection: A Prospective Randomized Study

Background and Aim: It remains unclear whether Helicobacter pylori eradication therapy affects the healing rate of iatrogenic ulcers following endoscopic mucosal resection (EMR) for gastric tumors. The aim of our study was to prospectively evaluate the effect of H. pylori eradication therapy on gastric ulcer healing after EMR. Methods: After EMR, patients were randomly assigned to either the H. pylori eradication group (Hp group) (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, twice a day for 7 days) or the noneradication group (proton pump inhibitor, PPI group) (lansoprazole 30 mg, twice a day for 7 days). Four weeks after EMR, the ulcer stages and size were compared between the two groups. Moreover, ulcer‐related symptoms, bleeding rates, adverse effects, and drug compliance were compared. Results: A total of 64 patients were enrolled. Of these, 17 patients were excluded from the study. The two groups were comparable in terms of baseline clinicopathologic characteristics. Four weeks after EMR, the two groups did not differ with respect to ulcer stage (p = .475) or ulcer‐related symptoms (p = .399). However, the ulcer reduction ratio was significantly higher in the Hp group (0.028 ± 0.024 vs. 0.065 ± 0.055, p < .05). No differences were observed between the two groups with regard to drug compliance, adverse drug event rates, or bleeding rates. Conclusions: Our results suggest that H. pylori eradication therapy might improve the ulcer healing rate after EMR.     

High Efficacy of 14‐Day Triple Therapy‐Based,Bismuth‐Containing Quadruple Therapy for Initial Helicobacter pylori Eradication

Background: The success rate of currently recommended 7‐day triple therapy with a PPI plus amoxicillin and clarithromycin has fallen into the unacceptable range. It is urgent to look for a new strategy to treat the infection of Helicobacter pylori. Aims: To observe the efficacy of triple therapy‐based, bismuth‐containing quadruple therapy for H. pylori treatment. Methods: A total of 160 patients with functional dyspepsia who were Hp+ were randomly assigned into two groups. Regimen: Omeprazole 20 mg, Amoxicillin 1.0 g, Clarithromycin 500 mg and Bismuth Potassium Citrate 220 mg, twice a day. Eighty patients received 7‐day quadruple therapy and 80 patients received the same therapy for 14 days. Six weeks after treatment, H. pylori eradication was assessed by ¹³C‐urea breath test. Minimal inhibitory concentrations of metronidazole, clarithromycin and amoxicillin of clinical isolates were determined by the twofold agar dilution method. Results: Fourteen‐day therapy led to a significant increase of H. pylori eradication success when compared to 7‐day therapy in the intention‐to‐treat analysis (93.7 vs 80.0%; p = .01), and the per‐protocol analysis (97.4 vs 82.0%; p = .0016). The H. pylori resistance rates to metronidazole, clarithromycin and amoxicillin were 42.1, 18.0 and 0%. Fourteen‐day therapy was significantly more effective in patients with clarithromycin‐resistant strains. Incidences of adverse events were comparable. Conclusions: Addition bismuth and prolonging treatment duration can overcome H. pylori resistance to clarithromycin and decrease the bacterial load. Fourteen‐day triple therapy‐based, bismuth‐containing quadruple therapy achieved ITT success rate 93% and could be recommended as the first line eradication regimen.     

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.     

The Effect of Probiotics and Mucoprotective Agents on PPI‐Based Triple Therapy for Eradication of Helicobacter pylori

Background/Aims: Recent studies have found that probiotics have anti‐Helicobacter pylori (HP) properties. We evaluated the additive effects of (i) Saccharomyces boulardii combined with proton pump inhibitor (PPI)‐based triple therapy and (ii) S. boulardii and a mucoprotective agent (DA‐9601) coupled with PPI‐based triple therapy for HP eradication. Methods: We recruited 991 HP infected patients and randomized them into one of three groups, (A) PPI‐based 7‐day triple therapy, (B) the same triple therapy plus S. boulardii for 4 weeks, and (C) the same 7‐day triple therapy plus S. boulardii and mucoprotective agent for 4 weeks. All patients in the three groups were tested via ¹³C‐urea breath test 4 weeks after the completion of the therapy. Results: According to the results of an intention‐to‐treat analysis, HP eradication rates for the groups A, B, and C were 71.6% (237/331), 80.0% (264/330), and 82.1% (271/330), respectively (p = .003). According to the results of a per protocol analysis, the eradication rates were 80.0% (237/296), 85.4% (264/309) and, 84.9% (271/319), respectively (p = .144). The frequency of side effects in group B (48/330) and C (30/330) was lower than that in group A (63/331) (p < .05). Conclusion: This study suggests that supplementation with S. boulardii could be effective for improving HP eradication rates by reducing side effects thus helping completion of eradication therapy. However, there were no significant effects on HP eradication rates associated with the addition of mucoprotective agents to probiotics and triple therapy.     

Eradication of Helicobacter pylori in children in Vietnam in relation to antibiotic resistance

Background: Low Helicobacter pylori eradication rates are common in pediatric trials especially in developing countries. The aim of the study was to investigate the role of antibiotic resistance, drug dosage, and administration frequency on treatment outcome for children in Vietnam. Materials and Methods: Antibiotics resistance of H. pylori was analyzed by the Etest in 222 pretreatment isolates from children 3–15 years of age who were originally recruited in a randomized trial with two treatment regiments: lansoprazole with amoxicillin and either clarithromycin (LAC) or metronidazole (LAM) in two weight groups with once‐ or twice‐daily administration. The study design was an observational study embedded in a randomized trial. Results: The overall resistance to clarithromycin, metronidazole, and amoxicillin was 50.9%, 65.3%, and 0.5%, respectively. In LAC, eradication was linked to the strains being susceptible to clarithromycin (78.2% vs 29.3%, p = .0001). Twice‐daily dosage of proton‐pump inhibitor (PPI) and clarithromycin was more effective for eradication than once‐daily dosage for resistant strains (50.0% vs 14.7%, p = .004) and tended to be so also for sensitive strains (87.5% vs 65.2%, p = .051). Exact antibiotic dose per body weight resulted in more eradication for resistant strains (45.3% vs 8.0%, p = .006). These differences were less pronounced for the LAM regimen, with twice‐daily PPI versus once daily for resistant strains resulting in 69.2% and 50.0% eradication (p = .096), respectively. Conclusions: Helicobacter pylori clarithromycin resistance was unexpectedly high in young children in Vietnam. Clarithromycin resistance was an important cause for eradication treatment failure. Twice‐daily administration and exact antibiotic dosing resulted in more eradicated infections when the strains were antibiotic resistant, which has implications for the study design in pediatric H. pylori eradication trials.     

Meta-Analysis: Lactobacillus Containing Quadruple Therapy Versus Standard Triple First-Line Therapy for Helicobacter pylori Eradication

Background:  Recent evidence showed that Lactobacilli could exert an inhibitory effect on Helicobacter pylori both in vitro and in vivo models. To systematically evaluate whether adding Lactobacilli to H. pylori eradication regimens could improve eradication rates and reduce side effects during anti- H. pylori treatment.
Materials and Methods:  Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing Lactobacilli supplementation to placebo or no treatment during anti- H. pylori regimens. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis analysis was also performed.
Results:  We identified eight randomized trials (n = 1372). Pooled H. pylori eradication rates were 82.26% (95% CI = 78.01–86.51%) and 76.97% (95% CI = 73.11–80.83%) for patients with or without Lactobacilli by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.78 (95% CI = 1.21–2.62). The occurrence of total side effects had no significant difference and were 30.84% (95% CI = 24.82–36.86%) and 42.24% (95% CI = 35.89%–48.59%) for two groups, the summary OR was 0.49 (95% CI = 0.24–1.02); However, Lactobacilli supplementation group had lower occurrence of diarrhoea, bloating and taste disturbance.
Conclusions:  Our review suggests that supplementation with Lactobacilli could be effective in increasing eradication rates of anti- H. pylori therapy for first-treated patients. Furthermore, Lactobacilli showed a positive impact on some H. pylori therapy-related side effects.     

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.     

Lafutidine versus Lansoprazole in Combination with Clarithromycin and Amoxicillin for One versus Two Weeks for Helicobacter pylori Eradication in Korea

Background and Aims: Lafutidine is a novel H₂‐receptor antagonist with gastroprotective activity that includes enhancement of gastric mucosal blood flow. The aim of the present study was to test the efficacy of 7‐ or 14‐day lafutidine–clarithromycin–amoxicillin therapy versus a lansoprazole‐based regimen for Helicobacter pylori eradication. Methods: Four hundred and sixty‐three patients with H. pylori‐infected peptic ulcer disease were randomized to one of four regimens: (1) lafutidine (20 mg b.i.d.), clarithromycin (500 mg b.i.d.) and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LFT group) or (2) for 14 days (the 14LFT group); (3) lansoprazole (30 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1000 mg b.i.d.) for 7 days (the 7LPZ group); or (4) for 14 days (the 14LPZ group). The eradication rates, drug compliance, and adverse effects among the four regimens were compared. Results: The eradication rates by the intention‐to‐treat and per‐protocol analyses in the 7LFT and 7LPZ groups were 76.5% and 81.6%, and 76.9% and 82.0% (p = .94 and .95), respectively. The eradication rates by intention‐to‐treat and per‐protocol analyses in the 14LFT and 14LPZ groups were 78.2% and 82.2%, and 80.4% and 85.9% (p = .70 and .49), respectively. The treatment duration for 7 days or 14 days did not affect the eradication rates. In addition, the adverse effect rates and discontinuation rates were similar among the four groups. Furthermore, the ulcer cure rate and symptom response rate were similar in the lafutidine and lansoprazole groups. Conclusion: The results of this study showed that lafutidine–clarithromycin–amoxicillin therapy was a safe and effective as lansoprazole‐based triple therapy for the eradication rate of H. pylori, and could be considered as an additional treatment option.     

Susceptibility of Helicobacter pylori Isolates against Agents Commonly Administered for Eradication Therapy and the Efficacy of Chemotherapy

Although chemotherapy has been documented to be effective in the treatment of Helicobacter pylori-associated gastritis and gastroduodenal ulcers, some cases are known to have been unsuccessful in the attempt to eradicate this species. In this study, we examined the relation between the susceptibility of H. pylori isolates and the efficacy of chemotherapy. We utilized the modified agar plate dilution method to determine the minimum inhibitory concentrations (MICs) of 63 H. pylori strains isolated before treatment with several drugs routinely used during eradication chemotherapy. Among the drugs tested, amoxicillin (AMPC) and clarithromycin (CAM) demonstrated high degrees of activity with MIC₉₀, 0.39 and 0.2 μg/ml, respectively. No highly resistant strain against AMPC was detected among the strains examined, while for CAM and metronidazole (MTZ), 9.5% and 7.9% of the strains, respectively, were resistant before treatment. It should be noted that all of the MICs of the strains from patients with successful therapy were lower than those from patients with unsuccessful therapy. These findings indicate that susceptibility tests should be carried out prior to the commencement of drug administration in order to provide safer and more effective chemotherapy.