Improving the success rate of Helicobacter pylori eradication therapy
In the past few decades, it has become apparent that recurrences of peptic ulcers can be prevented by eradicating Helicobacter pylori, a bacterial infection that occurs commonly in the stomach of ulcer patients. Treatment with a combination of antibiotics, acid blockers (proton pump inhibitors) and sometimes bismuth is often effective for eradicating this infection, but in a substantial minority of patients the infection persists despite treatment. New research has shown that certain dietary modifications and nutritional supplements can increase the success rate of conventional H. pylori eradication therapy. Interventions that have been reported to be successful include a low-nickel diet, supplementation with N-acetylcysteine, and administration of probiotics.
H. pylori contains a nickel-dependent urease enzyme. This enzyme catalyzes the hydrolysis of urea in gastric juice to form ammonia, an alkaline compound that protects H. pylori against gastric acidity. NiFe-hydrogenase is another nickel-dependent enzyme produced by H. pylori that helps the organism survive the acid environment of the stomach. In a randomized controlled trial, consumption of a low-nickel diet significantly increased the success rate in patients receiving conventional H. pylori eradication therapy.
Fifty-two patients with newly diagnosed H. pylori infection were randomly assigned to consume a standard diet or a diet in which all foods high in nickel content were prohibited. Starting on day 15 of the diet, all patients were treated with 15 mg of lansoprazole, 500 mg of clarithromycin, and 1,000 mg of amoxicillin, each twice a day for 7 days. H. pylori eradication was assessed by the urea breath test 4 weeks after the end of treatment. The eradication rate was significantly higher with the low-nickel diet than with the standard diet (84.6% vs. 46.2%; p < 0.01). Information on how to follow a low-nickel diet is available on the Internet.
H. pylori produces a protective matrix known as a biofilm. Biofilms are thought to promote antibiotic resistance by several different mechanisms, one of which is to block the penetration of antibiotics. N-Acetylcysteine (NAC) has been found to prevent biofilm formation in vitro and to promote the degradation of existing biofilm. In clinical trials, supplementation with NAC markedly increased the success rate of conventional eradication therapy, both in patients who had previously had multiple unsuccessful attempts to eradicate H. pylori and in those undergoing their first course of treatment.
Forty patients who had had at least 4 unsuccessful attempts to eradicate H. pylori were randomly assigned to receive NAC (600 mg once a day) or no NAC (controls) for 1 week, followed by a culture-guided eradication regimen that included 2 antibiotics and a proton pump inhibitor. The eradication rate was significantly higher in the NAC group than in the control group (65% vs. 20%; p < 0.01). Biofilm disappeared in all patients in whom eradication was successful, but persisted in patients in whom eradication was unsuccessful.
Seventy patients with H. pylori infection were randomly assigned to receive 500 mg of clarithromycin and 30 mg of lansoprazole, each twice a day, plus 10 ml (400 mg) of NAC liquid 3 times per day for 10 days, or clarithromycin and lansoprazole without NAC (control group). Eradication of H. pylori was assessed 1 month after the completion of treatment by performing a rapid urease test on gastric biopsy samples. The eradication rate was significantly higher in the NAC group than in the control group (50% vs. 23%; p = 0.034).
Based on these findings, adjunctive treatment with NAC should be considered for all patients undergoing H. pylori eradication therapy.
Administration of various probiotic agents has been reported to reduce the incidence of antibiotic-induced gastrointestinal side effects in patients with H. pylori infection. In addition a meta-analysis of 10 controlled trials found a significant increase in eradication rates when probiotics were added to conventional therapy. This beneficial effect may be due in large part to a decrease in antibiotic side effects, which would increase the proportion of patients who complete the full course of treatment. In addition, some probiotic organisms have demonstrated antibacterial activity against H. pylori. For example, L. acidophilus inhibited in vitro the growth of H. pylori isolated from gastric biopsy samples of patients with “acid-peptic disease.” Administration of L. salivarius also prevented gastric colonization of H. pylori in mice. While probiotics may decrease the side effects and enhance the efficacy of conventional treatment, there is no evidence that probiotic therapy by itself would be an effective treatment for H. pylori infection.
- Campanale M, et al. Nickel free-diet enhances the Helicobacter pylori eradication rate: a pilot study. Dig Dis Sci. 2014;59:1851-1855.
- Penn State Hershey. Milton S. Hershey Medical Center. Low nickel diet. http://www.pennstatehershey.org/c/document_library/get_file?uuid=0888ec6e-3d2f-4766-833e-b38bd920ffcd&groupId=102184. Accessed April 8, 2017.
- Dinicola S, et al. N-acetylcysteine as powerful molecule to destroy bacterial biofilms. A systematic review. Eur Rev Med Pharmacol Sci. 2014;18:2942-2948.
- Cammarota G, et al. Biofilm demolition and antibiotic treatment to eradicate resistant Helicobacter pylori: a clinical trial. Clin Gastroenterol Hepatol. 2010;8:817-820.e3.
- Gurbuz AK, et al. Effect of N-acetyl cysteine on Helicobacter pylori. South Med J. 2005;98:1095-1097.
- Myllyluoma E, et al. Probiotic supplementation improves tolerance to Helicobacter pylori eradication therapy – a placebo-controlled, double-blind randomized pilot study. Aliment Pharmacol Ther. 2005;21:1263-1272.
- Armuzzi A, et al. Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side effects during Helicobacter pylori eradication therapy: a pilot study. Digestion. 2001;63:1-7.
- Cremonini F, et al. Effect of different probiotic preparations on anti-Helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol. 2002;97:2744-2749.
- Wang ZH, et al. Meta-analysis of the efficacy and safety of Lactobacillus-containing and Bifidobacterium-containing probiotic compound preparation in Helicobacter pylori eradication therapy. J Clin Gastroenterol. 2013;47:25-32.
- Bhatia SJ, et al. Lactobacillus acidophilus inhibits growth of Campylobacter pylori in vitro. J Clin Microbiol. 1989;27:2328-2330.
- Kabir AM, et al. Prevention of Helicobacter pylori infection by lactobacilli in a gnotobiotic murine model. Gut. 1997;41:49-55.
Reprinted with permission from the Townsend Letter.