Update on H pylori Infection and Undifferentiated Dyspepsia

Family physicians frequently encounter patients who suffer from dyspepsia and who test positive for H pylori. This is not unexpected since it is estimated that half of the world's population is infected with this organism. Eradication of this organism is clearly helpful for patients who suffer from peptic ulcer disease where it has been demonstrated to reduce the incidence of bleeding and the rate of recurrence.

However, most patients that we see with H pylori infections do not have peptic ulcer disease, but rather undifferentiated dyspepsia. It is estimated that 30% of patients, in North America, with dyspepsia are infected. Risk factors include residence in a developing country, poor socioeconomic conditions, family overcrowding, and possibly an ethnic or genetic predisposition. In North America, the prevalence of H. pylori among Asian Americans, African Americans, and Hispanics is similar to that among persons in developing countries.¹

Because this condition is common, and because access to endoscopies is limited, a "test and treat" strategy has been recommended. Studies have shown that this strategy improves symptoms, is cost effective and reduces both the numbers of endoscopies and the number of antisecretory drugs administered.^2,3

When deciding to follow the "test and treat" strategy, it is important to watch for "red flags" that would mandate endoscopy. These would include such things as dysphagia, early satiety, protracted vomiting, anorexia, loss of more than 10 percent of body weight, melena, rectal bleeding, abdominal mass, previous peptic ulcer disease, jaundice, family history of gastric cancer.

The test most commonly used, because of its convenience, is serology for immunoglobulin G. This test is, however, less accurate than the urea breath test or the stool antigen test. Moreover, both of these later tests can be used to confirm eradication of the infection, whereas the serology test may remain positive for months after treatment. Breath urea testing is suggested as the investigation of choice for children. Use of PPIs, bismuth containing compounds and antibiotics can reduce the sensitivity of these tests.

Having decided to treat the patient, there are a myriad of regimens that can be used. There is some evidence that short course regimens are as effective as the longer courses, and may be advantageous in reducing cost to patients as well as the number of side effects.^4,5 It is unnecessary to continue antisecretory maintenance therapy in patients after H. pylori eradication.⁶

It is probably best for the practitioner to be familiar with one or two of the drug regimens, rather than trying to remember all of the combinations. The following are some typical regimens.

• PPI plus clarithromycin, 500 mg twice daily, or metronidazole, 500 mg twice daily, plus amoxicillin, 1 g twice daily for 10 days
• PPI plus metronidazole, 500 mg twice daily, plus clarithromycin, 500 mg twice daily for 10 days
• Bismuth subsalicylate, 525 mg four times daily, metronidazole, 250 mg four times daily, plus tetracycline, 500 mg four times daily for 2 weeks, plus H2-receptor antagonist therapy as directed for 4 weeks
• Bismuth subsalicylate, 525 mg four times daily, metronidazole, 250 mg four times daily, plus tetracycline, 500 mg four times daily, plus a PPI for 2 weeks

On occasion the patient will return to the office after treatment, with a recurrence of the symptoms. In this circumstance the question is whether the patient has a resistant organism ,or whether he/she has had a recurrence. Although first-line therapy will successfully eradicate the bacteria in most infected patients, antibiotic resistance of H. pylori is a growing concern.

Clarithromycin resistance is relatively common and is the major reason for lack of success in second-line therapy. This resistance cannot be overcome by increasing the dose of clarithromycin. Metronidazole resistance may be overcome by increasing the dose of metronidazole given when retreating.

If resistance is suspected a number of regimens have been suggested. Quadruple therapies that combine a PPI with bismuth-based triple therapy show an eradication rate of approximately 80%.

There is also data that supports the use of a repeat triple therapy with avoidance of one of the previously used antimicrobial agents.⁹

• Triple-drug therapy with pantoprazole 40 mg bid, amoxicillin 1 gm bid, and levofloxacin 250 mg bid for 10 days.
• Triple-drug therapy with PPI bid, amoxicillin 1 gm bid, and metronidazole 500 mg bid for 10 days
• Proton-pump inhibitors (standard dosage for 10 days), bismuth 240 mg twice daily, metronidazole 500 mg bid , and tetracycline 250 mg qid ^7,8,9

- John Hickey

Thanks to Dr Leo Pereira, Department of Internal Medicine at St. Martha's Regional Hospital in Antigonish Nova Scotia for reviewing the draft copy of this article.

References:

1. Adreinne Z. Ables Pharm.D.,I. Simon M.D., Emily R. Melton M.D., Update on Helicobacter pylori Treatment, American Family Physician Volume 75 Number 3 February 1, 2007 (Level 5 evidence, Review article)
2. Chiba N, Veldhuyzen Van Zanten SJ, Escobedo S, Grace E, Lee J, Sinclair P, et al Economic evaluation of Helicobacter pylori eradication in the CADET-Hp randomized controlled trial of H. pylori-positive primary care patients with uninvestigated dyspepsia. Aliment Pharmacol Ther 2004;19:349-58. (Level 3 evidence)
3. Lassen AT, Hallas J, Schaffalitzky de Muckadell OB Helicobacter pylori test and eradicate versus prompt endoscopy for management of dyspeptic patients: 6.7 year follow up of a randomised trial. Gut 2004;53:1758-63. (Level 1 evidence)
4. Lara LF, Cisneros G, Gurney M, Van Ness M, Jarjoura D, Moauro B, et al. One-day quadruple therapy compared with 7-day triple therapy for Helicobacter pylori infection. Arch Intern Med 2003;163:2079-84. (Level 3 evidence)
5. Treiber G, Wittig J, Ammon S, Walker S, van Doom LJ, Klotz U. Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med 2002;162:153-60. (Level 3 evidence)
6. Gisbert JP, Khorrami S, Carballo F, Calvet X, Gene E, Dominguez-Munoz JE. H. pylori eradication therapy vs antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. Cochrane Database Syst Rev 2004;(2):CD004062. (Level 3 evidence)
7. Hojo M, Miwa H, Nagahara A, Sato N. Pooled analysis on the efficacy of the second-line treatment regimens for Helicobacter pylori infection. Scand J Gastroenterol 2001;36:690Ð700. (Level 3 evidence)
8. Bilardi C, Dulbecco P, Zentilin P, Reglioni S, Iiritano E, Parodi A, et al. A 10-day levofloxacin-based therapy in patients with resistant Helicobacter pylori infection: a controlled trial. Clin Gastroenterol Hepatol 2004;2:997-1002. (Level 3 evidence)
9. Jason Collins, MD, Amira Ali-Ibrahim, MD, Duane T. Smoot, MD, FACP, FACG. Antibiotic Therapy for Helicobacter pylori Medical Clinics of North America Volume 90 Number 6 November 2006 (Level 5 evidence, review article)

You can search for abstracts of the above references by following this link: PubMed