Preventing Peptic Ulcer with Antibiotics

In recent years, researchers have shown that the natural history of peptic ulcer disease -- normally a chronic relapsing condition -- is markedly changed when H. pylori is cleared from the gastric mucosa by antibiotic therapy. Ulcers are healed, and recurrences are practically eliminated. In their two-year follow-up of 109 patients with healed duodenal or gastric ulcers, Graham et al showed that ulcer recurrence was significantly reduced in patients who had received triple-antibiotic therapy plus ranitidine, compared with patients who had received ranitidine alone (12% recurrence versus 95%, respectively, for patients with duodenal ulcer, and 13% versus 74% for patients with gastric ulcer). Of those patients who received ranitidine alone, 50% relapsed within 12 weeks of healing, and by the end of the study period, only three patients in the ranitidine-alone group were free of ulcer. In seven patients who received triple therapy, H. pylori was not eradicated; four of these had ulcer recurrence, the other three were lost to follow-up. Three patients with duodenal ulcer and two with recurrent gastric ulcer had relapses despite eradication of H. pylori; all were taking NSAIDs. Indeed, the only two risk factors for ulcer recurrence were chronic NSAID therapy and H. pylori infection; smoking and alcohol consumption, long thought to be associated with peptic ulcer disease, did not emerge as risk factors. Ten patients in the ranitidine-alone group who relapsed after ulcer healing were crossed over to triple therapy (plus ranitidine). The antibiotic regimen cleared H. pylori infection, and follow-up (ranging from 23 to 116 weeks) showed no relapses. Four patients with ranitidine-resistant ulcers were also crossed over to triple therapy and showed prompt healing with no relapse (follow-up: median, 40 weeks). The investigators recommended that "patients with resistant ulcers (defined as failure to heal in 12 weeks), those with ulcer-associated complications, and those with symptoms severe enough to be candidates for surgery receive triple therapy for H. pylori infection."
Graham DY. Ann Intern Med

Confirming H pylori eradication

Confirming H pylori eradication is difficult. Most tests require endoscopy, which is invasive, uncomfortable, time- consuming, and expensive. Urea breath tests are noninvasive and easy to perform, but the 13C test is expensive and the 14C test requires radioisotope handling, and neither are available yet in the US. Given the choices, most patients decline follow-up (unless there is a complication such as bleeding). Recently, Phull et al reported that there may be an easy way to confirm cure: ask the patient.

Phull et al studied 112 duodenal ulcer patients before and after treatment with antibiotics plus omeprazole or lansoprazole and/or colloidal bismuth subcitrate. At one and six months after completion of treatment, urea breath tests were administered and data collected on dyspeptic symptoms (epigastric discomfort, heartburn, nausea, vomiting, and gas). Absence of symptoms was considered indicative of successful eradication. At 6 months, there was a high correlation between dyspeptic symptoms and breath test results. Absence of symptoms was an excellent indicator of successful H pylori eradication; sensitivity was 97.5% and specificity 90.6%.
Phull PS et al. Brit Med J.

The Best Time to Take Bismuth-PeptoBismol, H pylori

When is the best time to take bismuth? Traditionally, patients have been advised to take colloidal bismuth (PeptoBismol) on an empty stomach to allow the compound to coat the stomach. However, a double-blind study by Webb et al suggests that bismuth compounds may be more effective when taken on a full stomach. The investigators studied the antimicrobial efficacy of ranitidine bismuth citrate in 40 patients with H pylori infection. Ranitidine bismuth citrate (Tritec/Glaxo) is a combination of ranitidine and bismuth citrate (bismuth 32% w/w). The combination has a dual mechanism of action; the bismuth component protects ulcer craters and is toxic to H pylori, while the ranitidine blocks H2 receptors on the acid-secreting parietal cell.
Patients with H pylori infection -- as indicated by a positive serum test 21 days prior to dosing and a positive urea breath test 60 minutes and 30 minutes prior to dosing -- were randomly assigned to ranitidine bismuth citrate (400 mg twice daily for 7 days). Half the patients took the drug combination 30 minutes prior to morning and evening meals (with a matching placebo taken 30 minutes after these meals), and half the patients took the combination 30 minutes after meals (with a matching placebo taken 30 minutes before meals). Food enhanced drug activity: 90% of patients who took the combination on a full stomach tested negative for H pylori on two consecutive 13C-urea breath tests, compared with only 55% of those who took it on an empty stomach. At follow-up in 3- 10 months, 14% of patients who took the combination on a full stomach were clear of H pylori compared with none of those who took the combination without food.The investigators suggest that food delays gastric emptying, prolonging the time that the bismuth component is in contact with the mucosa. Also, digestion mixes stomach contents, enhancing drug dispersal. The results of this study suggest that bismuth-containing preparations may be more effective when administered with food.

Webb DD et al. Am J Gastroent

Treating H pylori Infection

Medical experts now know that spicy foods and stress do not cause ulcers and that antacids and acid-suppressing drugs alone do not cure ulcers. What cures ulcers and prevents relapse is antibiotic therapy, preferably given in conjunction with an acid-suppressing drug to aid healing. H pylori is difficult to eradicate, so it usually takes two or more antibiotics to do the job. Studies have shown that dual or triple antibiotic therapy plus a histamine-2 (H2) receptor blocker or a proton-pump inhibitor (PPI) cures 85-90% of ulcer patients (H2 blockers inhibit the action of histamine, which normally stimulates acid production, and PPIs block the final step in acid production). Relapse is rare (less than 4% in studies in Europe, Australia, and the US).

H pylori is very sensitive to tetracycline and amoxicillin; it is resistant to vancomycin, nalidixic acid, trimethoprim, and sulfonamides; and it readily becomes resistant to metronidazole, and to a lesser extent to clarithromycin, if either drug is used alone. Bismuth salts have topical activity against H pylori; colloidal bismuth blocks bacterial enzymes, disrupts cell walls, prevents the organism from sticking to stomach tissue, and persists in the mucous in antimicrobial concentrations for about two hours following dosing. Bismuth subsalicylate (PeptoBismol) is the product available in the US; bismuth citrate is available abroad and under FDA evaluation here.

source: Walsh JH, Peterson WL. N Engl J Med

Helicobacter and Heart Burn

What about diagnosing the patient with benign functional dyspepsia? In the past, lab tests and/or endoscopy were used to rule out ulcers, but dyspepsia is so common and diagnostic costs are so prohibitive that many physicians are managing patients with empirical therapy. And many patients are managing themselves with a trip to the drug store.

One concern is that the availability of so many over-the-counter acid suppressants -- famotidine (Pepcid AC), cimetidine (Tagamet HB), and ranitidine (Zantac 75), as well as PeptoBismol and a large selection of antacids -- will allow patients to treat their own indigestion, which could be caused by H pylori infection and thus should be treated with antibiotics. When the urea breath test is available and diagnosing H pylori becomes a more routine part of medical care, self-diagnosis and self-treatment will be much less of a problem.

Urea breath test - Diagnosing H pylori Infection

One test that is widely available outside the US and under FDA evaluation in this country is the urea breath test, a sensitive, specific, and noninvasive test for H pylori. When an infected person swallows a dose of urea labeled with an isotope of carbon -- carbon-13 (13C) or carbon-14 (14C) -- H pylori in the gastric mucosa break down the labeled urea to form ammonia and labeled carbon dioxide. The carbon dioxide is absorbed into the bloodstream and excreted via the lungs. The patient then exhales into a device that measures the level of carbon dioxide. Of the two isotopes, 13C is safer because it is not radioactive, but it requires expensive instruments to detect it (a new generation of laser detectors may bring down costs). The 14C isotope uses a less expensive detector, but it emits beta radiation (although the amount emitted is a tiny fraction of the beta radiation that the average person is exposed to each year from natural sources). The urea breath test is specific for H pylori (it detects only urease-producing bacteria), it is sensitive (the labeled urea reaches a large area of the stomach and thus reflects total gastric urease activity), and the results can be reproduced.The urea breath:

Ultimately, the urea breath test should be approved and should be available for use in the doctor's office to provide a rapid diagnosis. In the mean time, doctors must rely on patient history, physical examination, lab tests, and radiography or endoscopy. Duodenal ulcers are usually benign, but gastric ulcers may be caused by a malignancy so endoscopic evaluation and biopsy of gastric ulcers are recommended, with repeat endoscopy to confirm healing.

source: Silverstein MD. Gastroent.

CLOtest Rapid Urease Test - Diagnosing H pylori

Each year, millions of patients visit their physicians complaining of digestive symptoms, most commonly functional dyspepsia ("indigestion") or gastroesophageal reflux ("heartburn"). However, many patients with abdominal discomfort are suffering from gastric or duodenal ulcers, which are commonly caused by H pylori and thus are curable. Clearing the infection usually heals the ulcer and prevents relapse, so an accurate diagnosis is important. There are several options for diagnosing H pylori infection: serology to detect antibodies against the bacterium; endoscopic biopsy for urease testing ( H pylori produce a urease that breaks down urea to ammonia and carbon dioxide); histology with special stains; or culture. Unfortunately, these procedures are invasive, expensive, or not always accurate. Serological tests require a blood sample and tell only that a patient has been exposed to H pylori at some time in the past, but not whether the patient is currently infected. Endoscopy and biopsy can detect current infection -- the CLOtest urease test allows rapid detection of H pylori in gastric biopsy specimens -- but endoscopy and biopsy are unpleasant medical procedures and require laboratory work. False negatives with these procedures range from 5 to 15%, so further testing may be required to rule out infection.