Helicobacter pylori treatment.

Helicobacter pylori is a Gram negative bacterium that was isolated in 1983 and has since been shown to be associated with peptic ulcer disease as well as gastric adenocarcinoma and gastric lymphoma. It has a worldwide prevalence. The rate of infection varies among different ethnic groups and socioeconomic strata. The overall prevalence in the United States is thought to be 10%. (1)

Treatment of H pylori usually consists of a combination of antibiotics along with an agent to reduce gastric acid. The regimens recommended by the American College of Gastroenterology (2) include a combination of a proton pump inhibitor (PPI), clarithromycin, and amoxicillin or metronidazole for 2 weeks. An alternate quadruple regimen includes bismuth subsalicylate, tetacycline, metronidazole, and a PPI or a H2-receptor blocker for 2 weeks. The efficacy of the above regimens in eradicating H pylori are 85 to 90%.

There is growing concern about antibiotic resistance to the currently used antibiotics. The prevalence of H pylori strains resistant to antibiotics in the United States have been estimated in two large trials. In the first trial, the resistance to metronidazole was 36% and between 22 and 39% (depending on method used) in the second trial. Resistance to clarithromycin was estimated to be 11 to 12%. A center in India recently reported that 85% of local strains were resistant to metronidazole. (3) Other problems include poor patient compliance with therapy and the numerous side effects of the antibiotics.

For patients failing therapy, one of the above alternate regimens can be tried. Other antibiotics like rifabutin, levofloxacin and furazolidone have shown promise in trials. Delivery systems to improve antibiotic concentration on the gastric surface are being developed. (4)

The gastric epithelium is covered by a 0.2 to 0.6 mm thick, viscous layer of mucus. This mucous gel is composed of water and mucin glycoproteins. H pylori resides in the stomach attached to the gastric epithelium and beneath this mucus layer. (1) Enzymes like phospholipases and proteases produced by the organism alter the mucus, presumably favoring colonization. (5)

In this issue of the Southern Medical Journal, Gurbuz et al investigate the idea of altering the mucus with N-acetyl cysteine (NAC) to improve antibiotic delivery. NAC reduces mucus thickness and decreases viscosity. In mice, NAC therapy has been shown to reduce H pylori load without preventing colonization. (6)

Gurbuz's study is a randomized controlled trial of 70 patients who presented with dyspepsia and were found to have H pylori infection on stomach biopsy. The trial group received NAC in addition to a 10 day regimen of clarithromycin and lansoprazole. Fifty percent (14/28) of the NAC group had eradicated the infection a month after treatment completion compared with 23% (7/30) in the control group. This difference was statistically significant.

The sample size in the study was small and further studies are needed to confirm the findings. Also, the eradication rate for clarithromycin and lansoprazole noted is less than that reported in other studies. (7) NAC is an unpleasant smelling liquid and compliance may be an issue.

With antibiotic resistance being increasingly reported, the value of NAC in H pylori therapy is potentially very significant. Certainly the idea of using a mucolytic to improve antibiotic delivery to the gastric mucosal surface is novel. It's a good idea and, despite the above limitations, has been nicely done in the study.

References

1. Peterson WL, Graham DY. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. Philadelphia, W.B. Saunders, 7th ed, 2002.

2. Howden CW, Hunt RH. Guidelines for the Management of Helicobacter pylori Infection Am J Gastro 1998;93:2330-2338.

3. Datta S, Chattopadhyay S, Patra R, et al. Most Helicobacter pylori strains of Kolkata in India are resistant to metronidazole but susceptible to other drugs commonly used for eradication and ulcer therapy. Aliment Pharmacol Ther 2005;22:51-57.

4. De la Torre PM, Torrado G, Torrado S. Poly (acrylic acid) chitosan interpolymer complexes for stomach controlled antibiotic delivery. J Biomed Mater Res B Appl Biomater 2005;72:191-197.

5. Nilius M, Malfertheiner P. Helicobacter pylori enzymes Aliment Pharmacol Ther 1996;10 (Suppl 1):65-71.

6. Huynh HQ, Couper RT, Tran CD, et al. N-acetylcysteine, a novel treatment for Helicobacter pylori infection. Dig Dis Sci 2004;49:1853-1861.

7. Logan RPH, Bardhan KD, Celestin LR. Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-center trial of omeprazole with or without clarithromycin. Aliment Pharmacol Ther 1995;9:417-424.

Murali Krishna, MD, and Judy Lalmuanpuii, MD

From Tarrytown, NY, and the Worthing Hospital, United Kingdom.

Reprint requests to Dr. Murali Krishna, 35 Hamilton Place, Tarrytown, NY, 10591. Email: [e-mail]

Accepted October 6, 2005.