Treatment strategies for Helicobacter pylori infection

Treatment strategies for Helicobacter pylori infection – includes patient information

Aristotle J. Damianos

Until recently, the dictum “no acid — no ulcer” dominated not only the premises underlying the pathophysiology of peptic ulcer disease but also its treatment.[1] The development of several selective histamine [H.sub.2]-receptor antagonists assisted the healing of acute peptic ulcers in most patients. However, the long-term management of peptic ulcer disease recurrence and the prevention of complications remained problematic. In 1983, Warren and [Marshall.sub.2] described finding curved organisms in patients with chronic gastritis. The subsequent demonstration that Helicobacter pylori is strongly associated with the development and natural history of peptic ulcer disease sparked a revolution in the treatment of this chronic disease.

Beyond temporary healing of the acute ulcer, therapy for peptic ulcer disease now offers the opportunity for long-term cure. A vast number of studies focusing on eradication of H. pylori have been published. These studies have resulted in a dizzying array of antibiotic and antisecretory regimens of varying dosages, combinations and durations. Numerous regimens have been met with initial enthusiasm, only to be found inadequate in larger series of patients. This article briefly reviews the epidemiology and diagnosis of H. pylori infection and focuses on appropriate drug therapy for peptic ulcer disease associated with Helicobacter infection.

Bacteriology and Epidemiology

H. pylori is a spiral-shaped, flagellated organism found predominantly in the gastric antrum (Figure 1). The organism burrows through the gastric mucous layer overlying the gastric epithelium. There it is protected from the acidic gastric milieu by the action of urease, an enzyme that cleaves gastric urea into ammonium ion and bicarbonate. Tissue injury occurs as a result of the local production of various cytotoxins and proteases and, possibly, through a cytotoxic effect of ammonia itself. Acute gastritis, a primarily polymorphonuclear inflammatory response in the lamina propria, occurs within two to three days following infection. Mononuclear cells, including lymphocytes and plasma cells, are also recruited and are capable of secreting IgA and IgG antibodies, which may be used to detect infection. Acquisition of H. pylori typically results in life-long infection and chronic antral gastritis.

Transmission of H. pylori infection most likely occurs through the fecal-oral route.[3] The prevalence of infection is related to socioeconomic conditions. In the United States, approximately 10 percent of whites below the age of 35 are infected, with rates increasing to almost 80 percent by age 75[4] (Figure 2). Prevalence rates for blacks are higher; 45 percent of those 25 years of age or less are infected. As a result of improvements in socioeconomic factors over the past few decades, children in the United States have a low overall prevalence of H. pylori infection. The increased prevalence of H. pylori infection in persons over the age of 50 represents remote chronic infection, not an increased susceptibility to infection acquired through aging.

Diagnosis of H. pylori infection can be made by invasive or noninvasive methods. In patients undergoing endoscopy, the rapid urease test is highly sensitive and specific. Histology is even more sensitive, but at a considerably higher cost. Currently, serology is the only widely available noninvasive method of diagnosis. Because antibody titers fall slowly and erratically, they are less useful in confirming eradication following treatment. Urea breath testing will be more widely available in the near future and is suitable for documenting both infection with and eradication of the organism.

Consequences of H. pylori Infection

Infection with H. pylori results in chronic gastritis in virtually all cases. Although histologic abnormalities are present, the gastritis is usually asymptomatic, and most infected persons suffer no further complications.

The most common clinically significant consequence of H. pylori infection is peptic ulcer disease, which develops in 10 to 20 percent of infected persons.[5-7] More than 90 percent of duodenal ulcers are associated with H. pylori infection.[8] Patients with duodenal ulcers not associated with Helicobacter are most likely to have injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) or Zollinger-Ellison syndrome, with hypersecretion of gastric acid. The association of H. pylori infection with gastric ulcers is also significant; 65 to 80 percent of gastric ulcers are associated with H. pylori infection.[8]

More than 90 percent of patients with adenocarcinoma of the distal stomach are seropositive for H. pylori. In the United States, infection with H. pylori has been estimated to confer a three-fold increase in the risk of adenocarcinoma of the stomach.[9] Most cases of low-grade gastric B cell lymphoma arising from mucosa-associated lymphoid tissue appear to be associated with H. pylori infection. While these associations are intriguing, it must be remembered that the prevalence of gastric malignancies in the United States is very low, while the prevalence of infection with H. pylori is high. Other factors in addition to H. pylori infection must play a role in the pathogenesis of gastric cancers.

Consequences of H. pylori Eradication

Eradication of H. pylori results in complete resolution of antral gastritis.[10] Whether this produces any symptomatic benefit to patients without concomitant ulcer disease is unclear. In contrast, the beneficial effect of H. pylori eradication on the course of peptic ulcer disease is now widely accepted. Successful treatment of H. pylori infection has a dramatic effect on the natural history of peptic ulcer disease. Eradication of H. pylori infection markedly reduces the recurrence rate of peptic ulcers (Figure 3).” It has been documented that this reduction in ulcer relapse persists for at least seven years following H. pylori eradication.[12] Figures for post-eradication relapses of gastric ulcers are similar. Re-bleeding from peptic ulcer disease has also been shown to decrease following eradication of the organism.[13]

As a result of the profound effect of H. pylori infection on the pathogenesis and natural history of peptic ulcer disease, the National Institutes of Health has issued a consensus statement outlining guidelines for the diagnosis and treatment of this infection (Table 1).[14] At present, no firm data support the eradication of H. pylori in either asymptomatic persons or those with nonulcer dyspepsia. The relationship between gastric cancers and H. pylori infection requires further investigation.


Guidelines for Routine Antimicrobial Treatment of Helicobacter pylori Infection

Negative for Positive for

Patient status H. pylori H. pylori

Asymptomatic No No

(no ulcer)

Nonulcer dyspepsia No No

Gastric ulcer No Yes

Duodenal ulcer No Yes

Drugs Used in the Treatment

of H. pylori Infection


Bismuth subsalicylate is the only bismuth preparation available in the United States. It is a bismuth salt that precipitates in the stomach and is active in the gastric lumen. Each tablet or 15-mL tablespoon of liquid contains 262 mg of bismuth and approximately 100 mg of salicylate. Unlike the bismuth fraction, most of the salicylate is absorbed into the blood stream. Because of a short half-life, dosing four times daily is preferred.

Bismuth alone possesses antibacterial properties and is frequently recommended for prophylaxis of traveler’s diarrhea. Repeated administration of bismuth does not induce bacterial resistance. The side effects of bismuth subsalicylate include black discoloration of the tongue and stools from the bismuth portion, and the potential for tinnitus from the salicylate moiety.


Tetracycline combined with bismuth and metronidazole (Flagyl) has yielded excellent H. pylori eradication rates. Tetracycline is not inactivated by acid pH and reaches high concentrations in the gastric mucosa. hi the treatment of most infections, tetracycline is taken on an empty stomach to prevent binding of the drug by divalent and trivalent cations. In patients with H. pylori infection, however, tetracycline is taken along with bismuth at meals, to promote binding of the drug to bismuth. This binding may result in increased delivery of the drug locally to the gastric mucous layer and thus improves the drug’s activity against the organism.”i Bacterial resistance to this inexpensive medication has not been reported; thus, in patients who have failed a first course of therapy, a regimen using tetracycline may be tried again. Side effects include diarrhea (both with and without Clostridium difficile) and photosensitivity.


Amoxicillin is an aminopenicillin that interferes with bacterial cell wall synthesis. It achieves high concentrations in gastric secretions and thus is considered to be luminally active. The activity of amoxicillin is markedly decreased by low pH, and it is ineffective in vivo when used as a single agent. Despite repeated exposure, H. pylori does not develop antibacterial resistance to amoxicillin. In addition to penicillin allergy, common side effects include diarrhea, candidiasis and, more rarely, C. difficile colitis.


Metronidazole is a bactericidal antibiotic that exhibits selective activity against anaerobes. It is secreted in gastric juices and also in saliva, and it is considered both locally and systemically active. It is not affected by pH. Most isolates of H. pylori in the United States are sensitive to metronidazole. It cannot be used as a single agent, however, since bacterial resistance rapidly develops.

Frequent side effects can hamper treatment with metronidazole. Although it protects against C. difficile colitis, up to 20 percent of patients taking it experience diarrhea. Nausea and vomiting are common, as is a metallic taste in the mouth. Patients should be cautioned that a disulfiram-like reaction may occur if they drink alcohol while taking metronidazole. Side effects increase with dosages above 1.5 g per day.


Like shorter acting erythromycin, this pH-independent macrolide inhibits bacterial protein synthesis by preventing elongation of protein chains. Both clarithromycin and its metabolite are active against H. pylori and are secreted in saliva. Clarithromycin fosters antibiotic resistance; therefore, it may not be used again following a treatment failure. Clarithromycin can replace metronidazole in any of the treatment regimens but is considerably more expensive. Side effects include diarrhea, nausea, headache and a bad taste in the mouth. Clarithromycin is contraindicated in patients also taking cisapride (Propulsid), an agent commonly used to treat gastroesophageal reflux, because of the risk of cardiac arrhythmias.


At dosages of 20 to 40 mg per day, omeprazole inhibits more than 90 percent of gastric add secretion. It does this by binding to the hydrogen-potassium ATPase on the apical aspect of the gastric parietal cell, the so-called proton pump. Omeprazole is thought to exhibit inherent antimicrobial activity against H. pylori, although its major contribution is in maintaining a more neutral gastric pH, thereby enhancing the activity of other antibiotics. Although it is expensive, omeprazole is generally well tolerated and has few side effects.

Lansoprazole (Prevacid), a newly available proton pump inhibitor, has not been studied extensively with regard to its effect on H. pylori. Trials are currently under way


[H.sub.2]-receptor antagonists have been the mainstay of ulcer treatment for the past 20 years. Their effect in H. pylori-associated ulcer disease is twofold. The first part is ulcer healing; although antibiotic therapy alone has been shown to heal peptic ulcers,19,20 symptomatic relief of ulcer pain is achieved much earlier, often within a few days, with the addition of antisecretory medication. Secondly, as noted above, increased intragastric pH improves the efficacy of many antibiotics. Comparisons of triple therapy using tetracycline show higher eradication rates when an an tory drug is also used.[17] A single tablet incorporating bismuth with ranitidine is now available as ranitidine bismuth citrate.

Specific Regimens


The most widely studied eradication regimens for H. pylori are those employing triple therapy using bismuth and metronidazole, plus either tetracycline or amoxicillin (Table 2). This triple therapy is the only r-egimen that has withstood the test of time in large numbers of patients in various geographic locations.


Regimens for Eradication of Helicobacter pylori Infection

Regimen 1: [Cost.subp.*] $45.00t; 16 to 17 pills per day for 14

days; success rate [is greater than] 90%.

Bismuth subsalicylate, 2 chewable tablets before meals

and at bedtime

Tetracycline or amoxicillin, 500 mg four times daily

Metronidazole (Flagyl), 250 mg three to four times daily

[H.sub.2] antagonist [double dagger] at bedtime

Comments: Take medications with meals; most infections cured after

one week of treatment

Regimen 2: [Cost.sub.*] $95.00; 16 pills per day for 14 days;

success rate [is greater than] 90%

Bismuth subsalicylate, 2 chewable tablets before meals

and at bedtime

Tetracycline or amoxicillin, 500 mg four times daily

Clarithromycin (Biaxin, 500 mg three times daily

[H.sub.2] antagonist at bedtime

Comments: Take medications with meals; most infections cured after

one week of treatment

Regimen 3: [Cost.sup.*] $95.00; 16 pills per day for 7 days; success

rate [is greater than] 90%

Bismuth subsalicylate, 2 chewable tablets before meals

and at bedtime

Tetracycline, 500 mg four times daily

Metronidazole, 500 mg three times daily

Omeprazole (Prilosec), 20 mg twice daily

Comments: Three days of pretreatment with omeprazole alone, then one

week of treatment with

antibiotics plus omeprazole

Regimen 4: [Cost.sup.*] $122.00 to $302.00; 13 pills per day for

10 to 14 days; success rate 86%

Amoxicillin, 750 mg three times daily

Clarithromycin, 500 mg three times daily

[H.sub.2] antagonist at bedtime

Comments: Take medications with meals; only small series reported

Regimen 5: [Cost.sup.*] $361.00; 5 pills per day for 14 days;

success rate 63 to 80%

Clarithromycin, 500 mg three times daily

Omeprazole, 40 mg daily

Comments: Take medications with meals; only small series reported

Regimen 6: [Cost.sup*] $199.00; 6 pills per day for 14 days; success

rate 88%

Clarithromycin, 250 mg twice daily

Omeprazole, 20 mg twice daily

Metronidazole, 500 mg twice daily

Comments: Nonrandomized, nonblinded studies

Regimen 7: [Cost.sup.*] $211.00; 2 to 5 pills per day for 28 days;

success rate 82%

Ranitidine bismuth citrate (Tritec), 400 mg twice daily

Clarithromycin, 500 mg three times daily

Comments: Clarithromycin given only during first two weeks;

FDA-approved regimen

Regimen 8: [Cost.sup.*] $66.00 to $132.00; 8 pills per day for 7 to

14 days; success rate 90%

Amoxicillin, 500 mg three times daily

Omeprazole, 40 mg daily

Metronidazole, 500 mg three times daily

Comments: Only small series reported

Regimen 9: [Cost.sup.*] $85.00 to $117.00; 6 pills per day for 10 to

14 days; success rate 37 to 90%

Amoxicillin, 1 g twice daily

Omeprazole, 20 mg twice daily

Comments: Wide variability in results even when drugs are started


FDA = U.S. Food and Drug Administration. NOTE: If an acute ulcer is not present, antisecretory medications may be eliminated from regimens I through 4, and 6. * — Estimated cost to the pharmacist based on average wholesale prices, rounded to the nearest dollar, in Red book. Montvale, N.J.: Medical Economics Data, 1997. Cost to the patient will be higher, depending on prescription filling fee. [Dagger] — Cost of regimen 1 is based on the lowest-priced options; if generic amoxicillin is used in place of tetracycline, the cost of regimen 1 is about $58.00. Bismuth is available in both caplets and chewable tablets, at varying prices. [Double dagger] — Cost based on price of ranitidine (Zantac). [Sections] — Cost of regimen 2 is based on the lowest-priced options; if generic amoxicillin is used in place of tetracycline, the cost of regimen 2 is about $309.00.

These medications should be taken with meals and at bedtime. Success rates of greater than 90 per-cent have been reported in most studies, although eradication rates are slightly lower when amoxicillin is used.[17] Metronidazole resistance reduces the success rate of triple therapy.[21] The prevalence of metronidazole-resistant strains varies widely from one geographic location to the next and is considerably higher in developing countries.[22] Metronidazole resistance may be higher in patients who have previously taken the drug. When clarithromycin is substituted for metronidazole, eradication rates are still greater than 90 percent.[23]

The optimal duration of therapy is not known. Treatment for less than one week produces inadequate results. There appears to be little difference in success rates between one-week and two-week regimens.[17] In one study, 53 (95 percent) of 56 patients were free of H. pylori infection after one week of triple therapy plus an H2-receptor antagonist, compared with 50 (94 percent) of 53 patients given a two-week course of therapy.[24]

Acid suppression is useful in triple therapy, both to rapidly relieve ulcer symptoms and to improve eradication of Helicobacter. Patients given triple therapy plus omeprazole report resolution of ulcer pain faster from those given triple therapy without omeprazole.[19] In a recent study, omeprazole was added to a seven-day course of bismuth, tetracycline and metronidazole, and eradication rates of 98 percent were achieved.[25] A direct comparison of omeprazole plus triple therapy versus H27receptor antagonists plus triple therapy has been published in abstract form.[26] Famotidine, 40 mg daily, added to triple therapy successfully eradicated H. pylori infection in 89 percent of patients. Omeprazole, 20 mg twice daily, improved this rate to 97 percent.

The major theoretic disadvantages to conventional triple therapy are side effects and compliance with taking a large number of pills daily Side effects have been reported to occur in up to 40 percent of patients using triple therapy. Most side effects are mild and self-limited. Only 5 percent of patients actually discontinue medication because of side effects.17 Poor compliance with triple therapy markedly reduces eradication success rates. Most studies suggest, however, that compliance with triple therapy is excellent if the physician impresses on the patient the importance of adhering to the prescribed regimen.


Amoxicillin plus omeprazole is the next most studied regimen, particularly in Europe, where it had been advocated as the initial therapy of choice. Unfortunately, it has been plagued by wide variations in reported success rates, which have dampened enthusiasm for its use. Relatively minor variations in dosages or dosing regimens have resulted in large discrepancies in reported eradication rates. Success rates may be lower if amoxicillin is initiated only after omeprazole. Factors thought to enhance H. pylori eradication with this regimen include (1) administering at least 40 mg of omeprazole per day in divided doses, (2) administering at least 2 g of amoxicillin per day and (3) treating the patient with this regimen for more than seven days. Two recent U.S. studies[27,28], using dual therapy with “optimal” dosing of omeprazole and amoxicillin produced eradication rates below 50 percent. Dual therapy with omeprazole and amoxicillin does not consistently eradicate H. pylori infection, and its use as an alternative to conventional triple therapy should be abandoned.

A single nonrandomized, noncontrolled British study[29] tested omeprazole, 40 mg daily, amoxicillin, 500 mg three times daily, and metronidazole, 400 mg three times daily Three hundred eight patients were treated for 14 days, and 80 patients were treated for seven days. Eradication rates for both groups were 90 percent; 49 percent experienced side effects, but only 3 percent discontinued treatment.


The combination of amoxicillin and clarithromycin, taken with meals and with an antisecretory drug, has been reported, in a small number of studies, to achieve eradication rates approaching 90 percent.[30] Treatment duration is 10 to 14 days. Roughly one third of patients experience mild side effects. The advantages of this regimen over triple therapy are that it is a simpler regimen and a smaller number of pills are involved. Further studies are needed before this regimen can be recommended for widespread use.



Ranitidine bismuth citrate, in a dosage of 400 mg twice daily for 28 days, eradicated H. pylori in 82 percent of patients with an active duodenal ulcer when combined with clarithromycin, 500 mg three times daily for the first 14 days.[31] The most common side effect, taste disturbance, was reported by 11 percent of subjects, with 5 percent discontinuing the regimen.


A few studies have focused on the use of clarithromycin, 500 mg three times daily, and omeprazole, 40 mg daily. Eradication rates have ranged from 63 to 80 percent.[32,33] A regimen,incorporating clarithromycin, 250 mg twice daily, and omeprazole, 20 mg twice daily, along with metronidazole, 500 mg twice daily, has been studied in a nonrandomized, nonblinded fashion in the United States. An 88 percent eradication rate was achieved in the 33 patients treated with this regimen for two weeks.[34] Side effects were experienced by 18 percent of the patients, but none required discontinuation of therapy.

Treatment Failures

Failure to eradicate H. pylori infection may derive from a number of causes. Poor compliance with antimicrobial therapy significantly reduces eradication rates. Patients who are smokers also seem to have lower eradication rates. Resistance to antibiotics, particularly metronidazole and clarithromycin, can lead to tr-eatment failures. Small variations in the dosing or timing of medications can significantly reduce success rates. For this reason, published treatment regimens must be rigorously adhered to.

Patients who have failed to complete at least one week of therapy or who have completed a course of antimicrobial therapy and are found to still be positive for H. pylori infection should be retreated with a different regimen.3 Metronidazole and clarithromycin should not be used twice in the same person, since both drugs promote bacterial resistance.

Treatment Recommendations

The goals of the treatment of peptic ulcer disease are to heal the ulcer, to relieve the patient’s symptoms and to reduce the potential for future relapse. Clinicians have long employed empiric therapy with [H.sub.2]-receptor antagonists, proton pump inhibitors or sucralfate (Carafate) in patients with uncomplicated disease presenting with epigastric pain, reserving more invasive diagnostic procedures for those who do not respond promptly to therapy. Ulcers ar-e healed with this treatment, and symptoms are often swiftly relieved whether an ulcer is actuary present or not. Recurrences of peptic ulcer disease, however, are frequent and can only be reduced by the elimination of H. pylori infection.

Since most patients with H. pylori infection never develop clinically significant disease and treated patients are exposed to the risk of antibiotic-associated complications such as pseudomembranous colitis, the empiric use of anti-Helicobacter therapy in the treatment of dyspepsia cannot be advocated at this time. Widespread empiric use of antibiotics may promote antibiotic resistance, making eradication of the organism even more difficult in the future.

Currently, no consensus exists on the evaluation of the patient presenting with dyspepsia. The NIH Consensus Panel on H. pylori has recommended that only patients with both documented ulcers and documented H. pylori infection be treated to eradicate the infection.[14] Others have argued that documenting the presence of ulcers is too costly and not necessary, given the efficacy of empiric treatment.[31]

We feel the approach to patients with dyspepsia should be individualized, taking into account the patients age, co-morbid conditions, risk factors for more serious disease and risk for Helicobacter infection. Young patients with dyspepsia may reasonably be treated empirically if found to be Helicobacter-positive by serology. Since the prevalence of H. pylori infection is low under the age of 50, fewer persons will be unnecessarily treated using this system than if all patients are given empiric therapy.

Endoscopy or contrast studies should be obtained in patients who do not respond to therapy within two weeks. Because of the high prevalence of H. pylori infection in persons over the age of 50 and the absence of ulcer disease in most of these persons, patients over the age of 50 should have documented ulcer disease before anti-Helicobacter therapy is initiated. Patients with evidence of gastrointestinal bleeding, weight loss, vomiting or severe persistent pain should also be initially evaluated with either endoscopy or an upper gastrointestinal series.

Treatment regimens should be tailored to meet the needs of individual patients. Most patients will have little difficulty tolerating and complying with conventional triple therapy, provided that the importance of strictly adhering to the regimen is explained by the physician. Triple therapy with tetracycline is the best choice for most patients. Amoxicillin can be substituted in patients with a contraindication to tetracycline. Clarithromycin should be used if there is a high incidence of metronidazole resistance in the community or if the patient has had previous exposure to metronidazole.

Treatment for 14 days is the gold standard, although in most patients the infection is eradicated after just one week. Compliant patients who suffer side effects after one week of therapy can stop treatment. Those who have not completed one full week of therapy should be switched to an alternate regimen. Patients with complicated ulcer disease or those who could ill afford to suffer another relapse should receive a full cou-rse of treatment.

Figure 2 is adapted with permission from Helicobacter pylori; the new factor in management of ulcer disease (slide set). Bethesda, Md.: American Digestive Health Foundation, 1994. Figure 3 is adapted with permission from Graham DY, Ginger ML, Klein PD, Evans DG, Evans DJ, Saeed ZA, et al. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric and duodenal ulcer. Ann Intern Med 1992;116:705-8.


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[2.] Warren JR, Marshall BJ. Unidentified curved bacilli on gastric epithelium in active chronic gastritis [Letter]. Lancet 1983;1(8336):1273-5.

[3.] Marshall BJ. Helicobacter pylori. Am J Gastroenterol 1994;89(Suppl 8):S116-28.

[4.] Marshall BJ. Epidemiology of H. pylori in Western countries. In: Hunt RH, Tytgat GNJ, eds. Helicobacter pylori: basic mechanisms to clinical cure. Boston: Kluwer Academic, 1994:75-84.

[5.] Marshall BJ. The 1995 Albert Lasker Medical Research Award. Helicobacter pylori. The etiologic agents for peptic ulcer. JAMA 1995;274:1064–6.

[6.] Sipponen P, Varis K, Fraki O, Korri UM, Seppala K, Siurala M. Cumulative 10-year risk of symptomatic duodenal and gastric ulcer in patients with or without chronic gastritis. A clinical follow-up study of 454 outpatients. Scand J Gastroenterol 1990;25:966-73.

[7.] Cullen DJ, Collins BJ, Christiansen KJ, et al. Long term risk of peptic ulcer disease in people with Helicobacter pylori infection — a community based study [Abstract]. Gastroenterology 1993;104(Suppl 2):A60.

[8.] Peterson WL. Helicobacter pylori and peptic ulcer disease. N Engl J Med 1991;324:1043-8.

[9.] Parsonnet J, Friedman GD, Vandersteen DP, Chang Y, Vogelman JH, Orentreich N, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 1991;335:1127-31.

[10.] Rauws, EA, Langenberg W, Houthoff FU, Zanen HC, Tytgat GN. Campylobacter pyloridis-associated chronic active antral gastritis. A prospective study of its prevalence and the effects of antibacterial and antiulcer treatment. Gastroenterol 1988,94:33-40.

[11.] Graham DY, Lew GM, Klein PD, Evans DG, Evans DJ Jr, Saeed ZA, et al. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study Ann Intern Med 1992;116:705-8.

[12.] Forbes GM, Glaser ME, Culten Dj, Warren JR, Christiansen KJ, Marshall Bj, et al. Duodenal ulcer treated with Helicobacter pylori eradication: seven-year follow-up. Lancet 1994;343:258-60.

[13.] Rokkas T, Karameris A, Mavrogeorgis A, Rallis E, Giannikos N. Eradication of Helicobacter pylori reduces the possibility of rebleeding in peptic ulcer disease. Gastrointest Endosc 1995;41:1-4.

[14.] NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ljlcer Disease. JAMA 1994;272:65-9.

[15.] Chiba N, Rao BV, Radenmaker JW, Hunt RH. Meta-analysis of the efficacy of antibiotic therapy in eradicating Helicobacter J Gastroenterol 1992;87:1716-27.

[16.] Fennerty MB. “Cure” of Helicobacter pylori and “cure” of peptic ulcer: do they mean the same thing? [Editorial]. Am J Gastroenterol 1995;90:12034.

[17.] Penston JG. Helicobacter pylori eradication — understandable caution but no excuse for inertia. Ahment Pharmacol Ther 1994;8:369-89.

[18.] Marshall BJ. Treatment strategies for Helicobacter pylori infection. Gastroenterol Clin North Am 1993;22:183-98.

[19.] Hosking SW, Ling TK, Chung SC, Yung MY, Cheng AF, Sung JJ, et al. Duodenal ulcer healing by eradication of Helicobacter pylori without anti-acid treatment: randomised controlled trial. Lancet 1994;343:508-10.

[20.] Sung JJ, Chung SC, Ling TK Yung MY, Leung VK, Ng EK, et al. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med 1995;332:139-42.

[21.] Zwet AA, Thijs JC, Oom JAJ, Hoogeveen K. Failure to eradicate Helicobacter pylori in patients with metronidazole-resistant strains. Eur J Gastroenterol Hepatol 1993;5:185-6.

[22.] Glupczynski Y, Burette A, De Koster E, Nyst JF, Deltenre M, Cadranel S, et al. Metronidazole resistance in Helicobacter pylori [Letter]. Lancet 1990;335: 976-7.

[23.] Graham DY, Ramirez FC, Lew GM, et al. Tetracychne, clarithromycin and bismuth: a new effective triple therapy for Helicobacter pylori eradication [Abstract]. Gastroenterol 1993;104:A90.

[24.] de Boer WA, Driessen WM, Potters VP, Tytgat GN. Randomized study comparing 1 with 2 weeks of quadruple therapy for eradicating Helicobacter pylori. Am J Gastroenterol 1994;89:1993-7.

[25.] de Boer W, Driessen W, Jansz A, Tytgat G. Effect of acid suppression on efficacy of treatment for Helicobacter pylori infection. Lancet 1995;345:817-20.

[26.] Borody TJ, Andrews P, Shortis NP Optimal H. pylori therapy: a combination of omeprazole and triple therapy [Abstract]. Gastroenterol 1994;106:A55.

[27.] Laine L, Stein C, Neil G. Limited efficacy of omeprazole-based dual and triple therapy for Helicobacter pylori: a randomized trial employing “optimal” dosing. Am J Gastroenterol 1995,90:1407-10.

[28.] Graham KS, Malaty H, el-Zimaity HM, Genta RM, Cole RA, al-Assi MT, et al. Variability with omeprazole-amoxicillin combinations for treatment of Helicobacter pylori infection. Am J Gastroenterol 1995,90:1415-8.

[29.] Bell GD, Powell KU, Burridge SM, Bowden AF, Atoyebi W, Bolton GH, et al. Rapid eradication of Helicobacter pylori infection. Aliment Pharmacol Ther 1995;9:41-6.

[30.] al-assi MT, Genta RM, Karttunen TJ, Graham DY. Clarithromycin-amoxicillin therapy for Helicobacter pylori infection. Ahment Pharmacol Ther 1994:8:453-6.

[31.] Fendrick AM, Chernew ME, Hirth RA, Bloom BS. Alternative management strategies for pafients with suspected peptic ulcer disease. Ann Intern Med 1995;123:260-8.

[32.] Tytgat GN. Treatments that impact favourably upon the eradication of Helicobacter pylori and ulcer recurrence. Aliment Pharmacol Ther 1994:8:359-68.

[33.] Logan RP, Gummett PA, Schaufelberger HD, Greaves RR, Mendelson GM, Walker MM, et al. Eradication of Helicobacter pylori with clarithromycin and omeprazole. Gut 1994;35:323-6.

[34.] Yousfi MM, el-zimaity HM, al-Assi MT, Cole RA, Genta RM, Graham DY. Metronidazole, omeprazole, and clarithromycin: an effective combination therapy for Helicobacter pylori infection. Aliment Pharmacol Ther 1995;9:209-12.

The Authors

ARISTOTLE J. DAMIANOS, M.D. is currently in private practice with a multispecialist group in Wausau, Wisc. A graduate of Dartmouth Medical School, Hanover, N.H., Dr. Damianos completed a residency in internal medicine at the Dartmouth-Hitchcock Medical Center, Hanover, and gastroenterology training at Pennsylvania State University College of Medicine, Hershey.

THOMAS J. MCGARRITY, M.D. is associate professor of medicine at the Pennsylvania State University Milton S. Hershey Medical Center. He graduated from the University of Virginia School of Medicine, Charlottesville. He completed a residency in internal medicine and a fellowship in gastroenterology at Pennsylvania State University College of Medicine.

Address correspondence to Aristotle J. Damianos, M.D., Wausau Medical Center, 2727 Plaza Dr., Wausau, WI 54401.

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