Helicobacter pylori eradication in patients with peptic ulcer disease: clinical consequences and financial implications.

We assessed clinical consequences and financial implications of Helicobacter pylori eradication in 175 patients with peptic ulceration, of whom 106 had been free from H. pylori infection for a mean of 3.2 years, while 69 remained infected. We used quarterly questionnaires to examine consumption of ulcer-healing medication and antacids. In the 106 successfully treated patients, gastrointestinal haemorrhage as a complication of peptic ulcer complications during the 344 patient years after eradication (0.003 per patient year) was 18-fold lower than during the 912 patient years before eradication (0.056 per patient year). Of the H. pylori-negative patients, 12-18% used ulcer-healing medication during any one of the three-month periods of the survey, compared with 34-51% of the patients with residual H. pylori infection. The average cost of the ulcer-healing drugs consumed by the H. pylori-negative patients was 30.59 pounds during the 12 months of the survey, compared with 99.05 pounds for H. pylori-positive patients. Consumption of antacids was also lower in the H. pylori-negative group. Successful eradication of H. pylori significantly reduced the annual cost of ulcer-healing drugs consumed by the patients with ulcer disease. Maintenance of ulcer remission following successful eradication of H. pylori also significantly reduced ulcer complications.

Helicobacter pylori eradication: efficacy and side effect profile of a combination of omeprazole, amoxycillin and metronidazole compared with four alternative regimens.

We evaluated eradication of Helicobacter pylori infection in 263 patients by a new 14-day regimen of omeprazole 40 mg mane (a gastric secretory inhibitor) plus two antibiotics: amoxycillin 500 mg three-times daily (tds) plus metronidazole 400 mg tds. The comparative groups included updated results of our previous work with a 14-day course of either standard triple therapy (STT, colloidal bismuth subcitrate 120 mg four times daily (qds) plus tetracycline 500 mg qds and metronidazole 400 mg tds), omeprazole 40 mg once daily plus amoxycillin 500 mg tds (OA), or two modified triple therapy: either Borody's (BTT) of all three components (colloidal bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 200 mg) qds instead of tds, or Logan's (LTT) seven-day therapeutic regimen of colloidal bismuth subcitrate 120 mg qds, amoxycillin 500 mg qds and, for the last three days, metronidazole 400 mg five times daily. Omeprazole/amoxycillin/metronidazole (OAM) therapy was better tolerated than STT (course completion 98.1% vs. 81.4%, p < 0.001). H. pylori was eradicated by OAM therapy in 53/55 (96.4%) patients with metronidazole-sensitive organisms and in 54/72 (75.0%) with metronidazole-resistant isolates (p < 0.01). The respective corresponding rates for STT and OA therapy were 20/22 (90.9%) and 14/29 (48.3%), (metronidazole-sensitive organisms) and 7/21 (33.3%) and 15/31 (48.4%) (infections resistant to metronidazole). BTT and LTT were also better tolerated than STT. The eradication rate for BTT was 23/26 (88.5%) but that for LTT, the best tolerated of the five treatment regimens, was only 19/28 (67.9%) when pretreatment isolates were metronidazole-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Reinfection or recrudescence after apparently successful eradication of Helicobacter pylori infection: implications for treatment of patients with duodenal ulcer disease.

Helicobacter pyloris is considered to be aetiologically implicated in gastritis and peptic ulceration, since if H. pyloris infection can be eradicated the risk of subsequent ulcer relapse is markedly reduced. The rate of 'reinfection' following treatment ranges from 0% to 45%, but its origin remains controversial (reappearance of uneradicated original infection or a fresh infection). To distinguish temporary suppression of H. pylori from fresh infection we conducted a retrospective analysis of the criteria used to establish eradication of the original infection in 304 patients. We used the [14C]urea breath test, in which an integrated area under the curve (AUC) value of < 40 in 2 h is considered to indicate eradication of H. pylori in patients tested 1 month after treatment. The results suggest that relapsed infection with H. pylori usually represents recrudescence of the original infection rather than a fresh infection; there was a higher relapse rate in patients with a breath test AUC > 20 < 40, compared with those with an AUC < 20. All 'reinfections' occurred within 24 months of the original treatment. 'Reinfection' was uncommon in patients receiving powerful therapeutic regimens (e.g. triple therapy) compared with those receiving monotherapy or relatively ineffective dual therapy combinations. In patients whose urea breath test remains negative 12 months after treatment the subsequent reinfection rate is only 0.44%/year. This supports the strategy of eradicating H. pylori infection from suitable peptic ulcer patients.

Biotype and molecular fingerprints of metronidazole-resistant strains of Helicobacter pylori from antral gastric mucosa.

Biotypes, ribosomal RNA gene restriction patterns (ribopatterns), whole-cell protein patterns and plasmid profiles of paired Helicobacter pylori isolates from 17 patients were examined. Each pair comprised a pre- and a post-treatment isolate; nine of the 17 post-treatment isolates were obtained after treatment with tripotassium dicitrate bismuthate (De-Nol) and metronidazole. All strains of H. pylori had identical biotypes, but exhibited diversity between pairs in their molecular fingerprints. Each of the 17 strain pairs had unique ribopatterns; the pre- and post-treatment isolates in most pairs (16 of 17) were similar or identical, irrespective of metronidazole susceptibility. DNA subtype variants were detected in three patient sets. Although nine post-treatment isolates had acquired resistance to metronidazole, most (six of nine) resembled the pre-treatment isolates in their ribopattern, protein and plasmid profiles. No significant correlation was observed between metronidazole resistance and plasmid content in these H. pylori isolates. Emergence of post-treatment metronidazole-resistant isolates of H. pylori was associated only rarely with colonisation by a novel strain or acquisition of a plasmid and, in most patients, probably resulted from spontaneous emergence of resistance in the original infecting strain.

Short report: omeprazole plus antibiotic combinations for the eradication of metronidazole-resistant Helicobacter pylori.

Twenty-eight Helicobacter pylori-positive patients with metronidazole-resistant isolates and 25 with metronidazole-sensitive isolates were treated for 14 days with 40 mg omeprazole nocte plus 500 mg amoxycillin t.d.s. Eradication of H. pylori, defined as absence of the organism one month after cessation of treatment, was assessed using the [14C]urea breath test. The eradication rate in patients with metronidazole-resistant isolates was 14/28 (50%) while that in patients was metronidazole-sensitive isolates was 12/25 (48%). In contrast to these encouraging eradication rates, very poor results were obtained with a 7-day course of omeprazole (40 mg nocte) in combination with erythromycin ethylsuccinate (500 mg q.d.s.) and tripotassium dicitrato bismuthate tablets (120 mg q.d.s.). The latter eradication rates were 3/20 (15%) in patients taking erythromycin tablets and 3/19 (16%) in those taking a liquid formulation of erythromycin. All treatment regimens were well tolerated and all patients completed the prescribed course of therapy.

Experience with 'triple' anti-Helicobacter pylori eradication therapy: side effects and the importance of testing the pre-treatment bacterial isolate for metronidazole resistance.

At the 1990 World Congresses of Gastroenterology, the Working Party on Helicobacter pylori (H. pylori) recommended that, in suitable patients, the bacterium should be eradicated using a therapeutic regimen comprising a bismuth salt, tetracycline and metronidazole for two weeks. We have treated 40 patients infected with H. pylori with 'triple' therapy consisting of 120 mg tripotassium dicitrato bismuthate q.d.s., 500 mg tetracycline q.d.s. and 400 mg metronidazole t.d.s. for two weeks. The success rate, in terms of bacterial eradication, was 19/21 (90.5%) in patients with metronidazole-sensitive organisms, compared with only 6/19 (31.6%) in patients whose H. pylori were resistant to metronidazole (P less than 0.01). Side effects, particularly diarrhoea and vomiting/nausea, were common: 23/40 patients reported such symptoms during the 14-day course of therapy. Fifteen of these 23 patients completed the entire 14-day course, although suffering from significant side effects, while the remaining eight patients had to discontinue the treatment because side effects became intolerable. If a form of triple therapy is going to be widely used to eradicate H. pylori infection, the regimen will have to be simpler, shorter, produce fewer side effects and be more effective in patients with metronidazole-resistant bacteria.

Does a previous course of tripotassium dicitrato bismuthate affect the subsequent chances of successful Helicobacter pylori eradication?

We have performed a retrospective study of 103 patients with either peptic ulcer or non-ulcer dyspepsia, infected with metronidazole-sensitive strains of Helicobacter pylori (H. pylori), who were treated with a combination of tripotassium dicitrato bismuthate and metronidazole for a period of at least two weeks. Dual therapy with tripotassium dicitrato bismuthate plus metronidazole showed similarly high eradication rates (greater than or equal to 80%) of H. pylori from patients irrespective of age, gender or clinical diagnosis. Most importantly, dual therapy achieved a similar eradication rate of H. pylori infection in 41 patients who had previously been treated with tripotassium dicitrato bismuthate alone or in combination with an antibiotic other than metronidazole. It therefore appears that H. pylori does not become resistant to treatment with tripotassium dicitrato bismuthate.

Helicobacter pylori: treatment with combinations of pivampicillin and tripotassium dicitrato bismuthate.

Fifty Helicobacter pylori- (H. pylori) positive patients entered an open study and were assigned to one of four treatment regimens comprising: pivampicillin (500 mg b.d.) for 2 weeks +/- tripotassium dicitrato bismuthate (tablet or liquid form) for one month. The 14C-urea breath test was used to evaluate clearance (negative at the end of treatment) and eradication (negative at 1 month post-treatment) of H. pylori. Clearance rates were 20% (2/10) after pivampicillin alone, 86% (12/14) after tripotassium dicitrato bismuthate tablets (240 mg b.d.) plus pivampicillin, 67% (6/9) after tripotassium dicitrato bismuthate tablets (120 mg q.d.s.) plus pivampicillin, and 100% (13/13) after tripotassium dicitrato bismuthate liquid (120 mg in 5 ml q.d.s) plus pivampicillin. The eradication rates were 0% (0/10), 13% (2/15), 0% (0/11) and 54% (7/13), respectively. Combination of the results from the 2 tripotassium dicitrato bismuthate tablet/pivampicillin groups gave an eradication rate of 7.7% (2/26) which was significantly lower than the 53.9% (7/13) obtained with tripotassium dicitrato bismuthate liquid/pivampicillin (P less than 0.02). In conclusion, a liquid tripotassium dicitrato bismuthate pivampicillin combination may be of special use in the treatment of H. pylori-positive patients when triple therapy is contraindicated (e.g. patient sensitivity/allergy to metronidazole) or when the H. pylori isolate is resistant to metronidazole.

Omeprazole and Helicobacter pylori: temporary suppression rather than true eradication.

Twenty-four Helicobacter pylori (H. pylori)-positive patients were treated for 28 days with either 20 mg omeprazole o.m. (n = 12) or 40 mg omeprazole o.m. (n = 12). Clearance (absence of H. pylori at the end of or shortly after treatment) and eradication (absence of H. pylori 1 month after cessation of treatment) were assessed using the 14C-urea breath test. Observed clearance and eradication were: 20 mg omeprazole 3/12 and 0/12; 40 mg omeprazole 6/12 and 1/12 respectively. The effect on H. pylori is probably due to the change in gastric pH from acid to neutral, however it is insufficient to recommend the inclusion of omeprazole in regimens aimed at eradicating H. pylori.

Helicobacter pylori infection treated with a tripotassium dicitrato bismuthate and metronidazole combination.

Seventy-two patients with H. pylori infection in their antral mucosa took part in the study. Forty-three received metronidazole 400 mg t.d.s. for two weeks, plus De-Nol tabs 2 b.d. for four weeks, and the remaining 29 patients received metronidazole 400 mg t.d.s. for two weeks plus De-Nol liquid 5 ml q.d.s. for four weeks. Seven of 57 H. pylori isolates were found to have pre-treatment metronidazole resistance. Success, in terms of eradication of H. pylori, was assessed using a one-month post-treatment 14C urea breath test. Successful eradication of H. pylori was achieved in 72% and 79%, respectively, of the metronidazole/De-Nol tablet and metronidazole/De-Nol liquid groups. These figures increased to 87% and 84%, respectively, if the patients whose organisms were known to be metronidazole-sensitive were considered in isolation. H. pylori was successfully eradicated in only one of seven patients with a metronidazole-resistant organism.