Noninvasive evaluation of Helicobacter pylori therapy: role of fasting or postprandial gastrin, pepsinogen I, pepsinogen II, or serum IgG antibodies.

OBJECTIVE: We evaluated the potential value of a change in serum IgG antibodies, fasting or meal-stimulated gastrin levels, and pepsinogen I (PGI) or pepsinogen II (PGII) levels for identifying Helicobacter pylori (H. pylori) status after antibiotic therapy. METHODS: A total of 32 men and one woman with peptic ulcer disease and documented H. pylori infection were enrolled. Fasting and 30-min postprandial blood samples were obtained at 0, 2, 7, 11, 17, 23, 27, and 39 wk of the study and were analyzed for the factors evaluated. RESULTS: Treatment was successful in 25 patients and failed in seven. Serum IgG antibodies, meal-stimulated gastrin, and both fasting and meal-stimulated pepsinogen I and II levels fell throughout the study, and pepsinogen I:II ratios increased in those whose infection was cured. The mean levels at wk 0 versus wk 7 were: fasting gastrin (fmol/ml) 12.4 and 11, meal-stimulated gastrin 26.5 and 15.4, PGI (ng/ml) 83.7 and 59, PGII (ng/ml) 24.5 and 13.6, PGI/PGII 3.5 and 4.7, and enzyme-linked immunosorbent assay value 4.8 and 4.55. The sensitivity, specificity, and positive and negative predictive values for the data analyzed using different percent changes (e.g., 80%, 50%, and 20%) were calculated. The specificity and sensitivity remained <80% at all time points. CONCLUSIONS: Despite a significant fall in serum markers of H. pylori infection in groups of individuals, no marker tested could be used to reliably determine posttherapy H. pylori status for individual patients.

Ulcer site and complications: relation to Helicobacter pylori infection and NSAID use.

BACKGROUND AND STUDY AIM: The aim of this study was to investigate the relationship between the presence and location of ulcers, H. pylori infection, NSAID use, and major upper gastrointestinal tract bleeding. PATIENTS AND METHODS: We studied 100 consecutive patients with duodenal ulcers and 145 consecutive patients with benign gastric ulcers. RESULTS: Ninety-nine percent of the duodenal ulcer patients and 92% of the gastric ulcer patients had H. pylori infection; all gastric ulcer patients without H. pylori infection were using NSAIDs. Gastric ulcers in patients with H. pylori infection who were not using NSAIDs were more likely to be on the lesser curvature (85%) than ulcers in NSAID users who had no H. pylori infection (35%) (p < 0.01). Conversely, only 5% of gastric ulcers in H. pylori-positive patients who were not using NSAIDs were on the greater curvature, compared to 45% in H. pylori-negative NSAID users (p < 0.01), and 23% in patients with both possible etiologies. The frequency of NSAID use was very high in patients presenting with upper gastrointestinal tract bleeding: 21 of 25 with gastric ulcers (84%) and 13 of 21 with duodenal ulcers (62%; p < 0.01 for each, compared to bleeding without taking NSAIDs). Overall, 74% of patients with upper gastrointestinal hemorrhage from peptic ulcer were taking NSAIDs. The prevalence of H. pylori infection was similar among the ulcer patients presenting with and without upper gastrointestinal tract bleeding. CONCLUSIONS: The location of a gastric ulcer on the greater curvature, and presentation with upper gastrointestinal tract bleeding, are separate and valuable clues to the involvement of NSAIDs. NSAID use may now be responsible for most bleeding complications of ulcer disease, regardless of H. pylori status.

Interobserver variation in the histopathological assessment of Helicobacter pylori gastritis.

The histopathologic detection of Helicobacter pylori in gastric biopsy specimens is considered the gold standard for the diagnosis of H pylori infection. However, few studies have addressed the pathologists' reliability to detect the organism and to assess the degree of the related inflammatory changes. The objectives of this study were to determine the degree of agreement among the findings of four gastrointestinal pathologists in the semiquantitative evaluation of H pylori infection and gastritis. Three slides from specified areas of the stomach of 99 patients with and without H pylori infection were stained with the triple stain, coded, and examined independently by four pathologists. For each specimen, a visual analogue scale graded from 0 (absent/normal) to 5 (maximal intensity) was used to score (1) H pylori (2) neutrophils, and (3) atrophy. Data were analyzed using kappa-statistics. The kappa-coefficient for the detection of H pylori (present vs absent) was approximately .9 (excellent); for the intensity of infection, it was considerably lower on the 6-point scale (approximately .61) and improved slightly on an amalgamated 4-point scale (approximately .71). The agreement on presence or absence of neutrophils was excellent (kappa = .8) in antral biopsies and good (kappa = .67) in corpus biopsies. The kappa for the semiquantitative scoring of neutrophils was poor on the 6-point scale (approximately .43) and fair on the amalgamated scale (approximately .54). The interobserver agreement was the poorest in the evaluation of atrophy (presence, absence, categories, or group categories) with kappa coefficients varying from .08 and .29. This group of pathologists had a high level of concordance on the diagnosis of H pylori infection in any particular patient and a high index in the assessment of the intensity of infection. The agreement was less in the semiquantitative evaluation of active inflammation. When the evaluation concerned a loosely defined feature, such as atrophy, there was essentially no agreement among the pathologists. This study suggests the need for further assessments of pathologists' ability to provide reproducible diagnoses. These results also indicate that more stringent criteria for the diagnosis of "soft" histopathologic features (such as atrophy) are urgently needed.

Confirmation of successful therapy of Helicobacter pylori infection: number and site of biopsies or a rapid urease test.

BACKGROUND: Although a number of tests have been described to detect the presence of Helicobacter pylori in biopsy specimens, studies of positive and negative value have largely been performed on untreated patients; testing the reliability of posttherapy has not been done. METHODS: We examined the value of the number and site of biopsies performed and the method used for specimen evaluation posttherapy. For postantimicrobial therapy of 141 patients with previously confirmed H. pylori infection, three biopsies were taken, two from the antrum and one from the corpus. Individual slides were coded, randomized, and interpreted blindly by two pathologists. Furthermore, in 143 patients, a biopsy specimen was taken from the antrum and was immediately inserted into the gel of the rapid urease test, and the results were compared with those obtained from histopathology obtained at the same time. RESULTS: In 71 patients, H. pylori therapy was unsuccessful; in 61 (86%), all three sites were positive. The highest yield with a single large cup biopsy specimen was 94%; the lowest was 91%. Two antral biopsies were negative in 4% [95% confidence interval (CI) = 1-12%]. The combination of a biopsy from the angulus incisura and one from the greater curvature of the corpus correctly identified all treatment failures (95% CI = 95-100%). The rapid urease test was false-negative in 5% (95% CI = 1-13%); there were no false-positives. CONCLUSION: Use of either the rapid urease test or two antral biopsies for evaluation of success of antimicrobial therapy for H. pylori infection will result in a false declaration of cure in at least 5% of cases. Three large cup gastric mucosal biopsies for histology are recommended for evaluation of the success of anti-H. pylori therapy.

Treatment of Helicobacter pylori infection with omeprazole-amoxicillin combination therapy versus ranitidine/sodium bicarbonate-amoxicillin.

OBJECTIVES: Simpler, effective therapies to treat Helicobacter pylori infection are greatly needed. Omeprazole co-therapy apparently enhances effectiveness of some antimicrobials. Our objective in this study was to determine whether the apparent additional benefit provided by omeprazole to amoxicillin therapy could be equaled by a high dose of ranitidine plus sodium bicarbonate. METHODS: In a prospective randomized trial, we tested 1 g amoxicillin b.i.d. with either omeprazole 20 mg b.i.d., or high dose ranitidine (900 and 1800 mg) plus sodium bicarbonate tablets 650 t.i.d. (with meals) for 14 day. RESULTS: Fifty-two patients with documented H. pylori infection and peptic ulcer completed therapy. The cure rate with omeprazole and amoxicillin was poor (46%), with the 95% confidence interval (CI) = 25-67%. Ranitidine plus sodium bicarbonate was also poor (39% cure) with the 95% CI = 21.5-59% (p > 0.57). Average compliance was more than 92% for all three groups. Side effects were experienced in only two patients (stomatitis and mild diarrhea). CONCLUSION: Neither the omeprazole nor ranitidine plus bicarbonate plus amoxicillin therapies used here can be recommended for treatment of H. pylori infection.

Variability with omeprazole-amoxicillin combinations for treatment of Helicobacter pylori infection.

OBJECTIVE: Although omeprazole co-therapy enhances the effectiveness of some antimicrobials for the treatment of Helicobacter pylori infection, results have not been uniform. A meta-analysis suggested that 20 mg of omeprazole b.i.d. and 2 g or more of amoxicillin would yield a > 80% success rate (Gastroenterology 1994; 106: 142A). Our objective in this study was to test that hypothesis. METHODS: Volunteers with H. pylori infection were studied. Anti-H. pylori therapy was administered with meals for 14 days (omeprazole 20 mg b.i.d. plus amoxicillin 1 g t.i.d., or omeprazole 20 mg b.i.d. plus amoxicillin 0.5 g t.i.d.). Endoscopy was performed 4-6 wk after antimicrobial therapy ended, and the presence or absence of H. pylori was determined with biopsy specimens by Genta stain. RESULTS: Fifty-nine volunteers completed the study; 30 were studied twice. The overall success for initial treatment with either combination of amoxicillin and omeprazole was 18 of 59 [30.5%; 95% confidence interval (CI) = 19-44%]. The success rate with 500 mg amoxicillin t.i.d. was 7 of 29 (24%; 95% CI = 10-43%). With 1 g t.i.d. amoxicillin, the cure rate was higher (36.6%) (11 of 30; 95% CI = 20-56%), or intention-to-treat result was 11 of 31 (35.4%), which includes the early dropout. Compliance was > 95% for both therapies. Side effects were experienced by eight patients, two receiving 1.5 g amoxicillin and six receiving 3 g amoxicillin (p > 0.2). German trials suggest that better results might be achieved when amoxicillin is given as suspension while fasting. Thirty treatment failures were re-treated with 1 g amoxicillin suspension t.i.d., given fasting, and omeprazole 20 mg b.i.d. The cure rate was 16.6% (95% CI = 6-35%). CONCLUSION: Amoxicillin/omeprazole combinations for treatment of H. pylori infection do not yield consistent results. The reason is unknown, but the reported high rate of success with 40 mg of omeprazole and 750 mg t.i.d. suggests that almost complete inhibition of acid secretion is necessary to obtain consistent results with this combination.

Metronidazole, omeprazole and clarithromycin: an effective combination therapy for Helicobacter pylori infection.

BACKGROUND: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multi-drug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole. METHODS: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks. RESULTS: Thirty-three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole-based triple therapy and eight with macrolide-based therapy (five with clarithromycin-based therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%-96%) including 90% of those who had failed previous anti-H. pylori therapies. Mild side effects were reported by 18%. CONCLUSION: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.

Azithromycin triple therapy for Helicobacter pylori infection: azithromycin, tetracycline, and bismuth.

BACKGROUND: Azithromycin is new acid-stable macrolide that achieves 10- to 40-fold higher tissue levels than erythromycin after oral dosing. Important to note, the tissue half-life of azithromycin is measured in days instead of hours. METHOD: We evaluated two new triple therapies for Helicobacter pylori infection in which azithromycin was substituted for metronidazole either as 250 mg b.i.d. or t.i.d. along with tetracycline 500 mg q.i.d. and bismuth subsalicylate 2 tablets q.i.d. for 14 days. H. pylori status was determined by histology before and 6 wk or more after therapy. RESULTS: Thirty men with documented H. pylori peptic ulcers completed therapy. Twenty-one also received ranitidine (300 mg in the evening) along with the antimicrobial therapy. H. pylori infection was successfully treated in 15 (50%) (95% CI = 31-69%). The cure rate was significantly higher with the 250-mg-t.i.d.-azithromycin dosage regime (83%) (95% CI = 52-98%) compared to the 250-mg-b.i.d.-dosage regime (28%) (95% CI = 10-53%) (p < 0.01). Troublesome side effects were experienced by the majority of those receiving azithromycin t.i.d. CONCLUSION: We conclude that although 750 mg or more of azithromycin might eventually be able to replace metronidazole or clarithromycin in standard triple therapy, additional studies are required to identify a regime that is both effective and tolerable.

Clarithromycin, tetracycline, and bismuth: a new non-metronidazole therapy for Helicobacter pylori infection.

OBJECTIVE: Metronidazole resistance has become an increasing problem that has limited the usefulness of the original triple therapy. Our objective was to evaluate clarithromycin, a new macrolide compound active against Helicobacter pylori. METHODS: We evaluated a new clarithromycin triple therapy for H. pylori infection consisting of the combination of clarithromycin (500 mg t.i.d.), tetracycline (500 mg q.i.d.), and bismuth subsalicylate tablets (2 q.i.d.) for 14 days. Patients with ulcer also received concomitant ranitidine, 300 mg after the evening meal, for 6 wk. RESULTS: Thirty men with documented H. pylori infection were studied; 29 had peptic ulcer disease. Seven had previously failed antimicrobial therapy, including three with metronidazole-based triple therapy. H. pylori status was determined by histology. H. pylori status and ulcer status were evaluated 4 wk after the end of antimicrobial therapy. The ulcer was healed in 90%. The H. pylori infection was cured in 93%, including all three patients who previously failed metronidazole-based triple therapy. CONCLUSION: We conclude that the combination of clarithromycin, tetracycline, and bismuth is an effective new therapy for treatment of H. pylori infection.

Clarithromycin-amoxycillin therapy for Helicobacter pylori infection.

BACKGROUND: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection. METHODS: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. RESULTS: H. pylori infection was cured in 86% (95% CI = 78-99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects. CONCLUSION: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections.

Short report: omeprazole-tetracycline combinations are inadequate as therapy for Helicobacter pylori infection.

BACKGROUND: Current triple antimicrobial therapies cure Helicobacter pylori infection in 60-90% of cases but are cumbersome. Addition of omeprazole to amoxycillin has been shown to enhance effectiveness when compared to amoxycillin alone. METHOD: We studied omeprazole 20 mg t.d.s. plus tetracycline 500 mg q.d.s. for 14 days (OMP/TCN) and omeprazole 40 mg in the morning plus tetracycline 500 mg q.d.s. along with bismuth subsalicylate tablets 2 q.d.s. (OMP/TCN/BSS) for 14 days. Forty-four patients (19 OMP/TCN, 25 OMP/TCN/BSS) with H. pylori peptic ulcer disease were studied. H. pylori status was evaluated at least 4 weeks after ending antimicrobial therapy. RESULTS: In the OMP/TCN group cure of H. pylori infection was achieved in 5/19 (26%). Adding bismuth to the regimen improved the results; 4 weeks after ending therapy cure of H. pylori infection was achieved in 12/25 (48%). CONCLUSIONS: Neither regimen can be recommended for routine cure of H. pylori infection. Although one cannot predict which antimicrobial therapies will be enhanced by the addition of omeprazole, these data suggest that future studies should evaluate drugs whose effectiveness is compromised by low pH.

Peptic ulcer disease, Helicobacter pylori, and the surgeon: changing of the guard.

The ability to assign causative roles to Helicobacter pylori and nonsteroidal anti-inflammatory drug use in peptic ulcer disease, and proof that eradication of H. pylori infection results in cure of peptic ulcer disease, are resulting in a reassessment of the indications for surgery and the type of surgery to be performed. With only a few exceptions, surgery is rapidly becoming an outdated approach to the management of peptic ulcer disease. We will soon see the day when surgeons with great technical skill in peptic ulcer disease will be rare, just as it happened when chest surgeons were no longer needed for the management of chronic pulmonary infections.