Adjuvant antibiotic therapy in duodenal ulcers treated with colloidal bismuth subcitrate.

Persistence of Helicobacter pylori after duodenal ulcer healing is associated with high rates of ulcer relapse. We compared colloidal bismuth subcitrate alone with CBS combined with one of four antibiotic regimens in the treatment of duodenal ulcers. Endoscopy and antral biopsies were performed before treatment and four weeks afterwards. Biopsy specimens were examined for histological evidence of gastritis and by Gram stain and culture for H pylori infection. Altogether 141 patients were allocated to one of five treatment groups. Giving CBS and metronidazole (400 mg tid for 7 days) with and without amoxycillin (500 mg tid) achieved higher clearance rates of H pylori than treatment with CBS alone (p less than 0.01). These two combinations also achieved higher rates of antral gastritis healing than CBS alone (p less than 0.01 and p less than 0.05 respectively). Susceptibility to metronidazole was tested in 29 isolates before and in seven isolates after treatment with metronidazole by disc diffusion test and minimum inhibitory concentration assay. Twenty seven (93%) of the isolates were sensitive before treatment while six of seven (86%) were resistant afterwards. Four of the six resistant strains had acquired resistance during treatment and one of these had acquired metronidazole resistance despite concomitant treatment with amoxycillin, to which it remained sensitive. CBS with adjuvant metronidazole at a dose of 400 mg tid for seven days significantly improves the eradication of H pylori compared with CBS alone. Acquired metronidazole resistance, however, seems to be an important cause of failure to eradicate H pylori.     

One week's anti-Helicobacter pylori treatment for duodenal ulcer.

This open study tested whether eradication of Helicobacter pylori (H pylori) heals duodenal ulcers as well as decreasing recurrence. H pylori was detected in patients with endoscopic duodenal ulcers by histology, CLO-test, culture, and 13C-urea breath test (13C-UBT). Tripotassium dicitrato bismuthate (120 mg) and amoxycillin (500 mg) each four times daily, were given for seven days, with 400 mg metronidazole five times a day on days 5-7. The 13C-UBT was repeated immediately after treatment and endoscopy repeated within 21 days. After treatment unhealed ulcers were reinspected one month later and healed ulcers followed up by 13C-UBT alone for 12 months. Of 45 patients, 44 were available for follow up. Mean pretreatment excess delta 13CO2 excretion was 25.6 per mil, which fell to 2.4 per mil immediately after finishing treatment, indicating clearance of H pylori in every patient. At the second endoscopy (median interval 20 days from start of treatment) 33 of 44 (75%) duodenal ulcers had healed. Ten of the remaining 11 duodenal ulcers were smaller and those 10 healed in the next two weeks with no further treatment. Two patients' ulcers that initially healed with clearance of H pylori recurred three weeks later (both had metronidazole resistant H pylori). H pylori was eradicated in 28 of 44 (64%) patients (13C-UBT negative for median follow up 10.2 months). Overall 41 of 43 (93%, 95% confidence intervals 81%-99%) duodenal ulcers were healed at one month. This study suggests that one week of anti-H pylori triple treatment is effective in healing duodenal ulcers.     

Effect of Helicobacter pylori eradication on gastric metaplasia of the duodenum.

Helicobacter pylori associated duodenal ulcers occur in patches of gastric metaplasia. The pathogenesis of gastric metaplasia is unclear, but it has been produced in experimental animals by acute injury and has been shown to be present to a greater extent of H pylori positive subjects. This study aimed to discover if gastric metaplasia regressed with eradication of H pylori or healing of duodenal ulcers, or both. Thirty two duodenal ulcer patients with H pylori infection confirmed by biopsy urease test and by antral histological examination were studied. Patients were treated with triple therapy (deNol 240 mg twice daily, amoxycillin 500 mg three times daily, and metronidazole 400 mg three times daily) for two weeks after the first endoscopy and were subsequently re-endoscoped. Three duodenal bulb biopsy specimens were obtained per patient at each endoscopy. Biopsy sections were stained with haematoxylin and eosin to determine the severity of duodenitis, and with diastase periodic acid-Schiff/alcian blue to assess the extent of gastric metaplasia. Slides were assessed by two histopathologists unaware of treatment status. H pylori was eradicated in 63% of subjects and all ulcers were healed at follow up. The median extent of gastric metaplasia at the start of treatment and 6-18 months (median 10) after treatment was compared in the two groups. Gastric metaplasia declined in eradicators from 16% to 8% (p < 0.05) while in non-eradicators there was no significant change (25% initially and at follow up). A positive relation between extent of gastric metaplasia and duodenal inflammation score was present before treatment (r(s) = 0.74, p < 0.001) and was unchanged after treatment in the non-eradicator group (r(s) = 0.89, p < 0.001). In the eradicator group, however, the inflammation score had significantly declined (p < 0.02) and the close relation with gastric metaplasia was no longer present. These results suggest that H pylori itself is at least in part responsible for producing gastric metaplasia of the duodenum.     

Ranitidine Bismuth Citrate With Clarithromycin Given Twice Daily Effectively Eradicates Helicobacter pylori and Heals Duodenal Ulcers

Objective : Ranitidine bismuth citrate (RBC) b.i.d. with Clarithromycin q.i.d. eradicates Helicobacter pylori (H. pylori ) in 82–94% of patients, and heals duodenal ulcers in 88–90% of patients. This double blind, placebo-controlled study examines the efficacy of a simpler b.i.d. treatment regimen, and examines the potential benefit of including a second antibiotic, metronidazole, to the b.i.d. treatment regimen. Methods : A total of 648 patients with active duodenal ulcer received RBC 400 mg b.i.d. for 4 wk, coprescribed with Clarithromycin 250 mg q.i.d. , Clarithromycin 500 mg b.i.d. , or Clarithromycin 500 mg b.i.d. with metronidazole 400 mg b.i.d. for the first 2 wk of treatment. Endoscopies were performed prestudy, after 4 wk of treatment, and at least 4 wk posttreatment. H. pylori status was assessed by CLOtest, ¹³C-urea breath test (UBT), and histology prestudy, and by UBT and histology at least 4 wk posttreatment. Adverse events were recorded at each visit. Results : All three regimens were highly effective and well tolerated. H. pylori eradication rates were 84–94% and duodenal ulcer healing rates were 92–96% (observed data). Highest H. pylori eradication and ulcer healing rates were achieved with RBC 400 mg b.i.d. with Clarithromycin 500 mg b.i.d. Conclusion : Ranitidine bismuth citrate with Clarithromycin 500 mg b.i.d. provides an effective, simple and well tolerated regimen for the eradication of H. pylori and healing of duodenal ulcers.     

Detection of the intragastric sites at which Helicobacter pylori evades treatment with amoxycillin and cimetidine.

Treatment of Helicobacter pylori infection with amoxycillin is known to reduce the bacterial load to undetectable levels, while not eradicating the infection. It seems, therefore, that bacteria escape treatment at a 'sanctuary site'. This study examined whether such a site existed in the gastric antrum, body, or fundus. Twenty two patients with H pylori infection and duodenal ulcer disease were treated for one week with amoxycillin (500 mg three times a day) and cimetidine (800 mg at night). Before treatment, H pylori was detected throughout all stomachs, and 13C-urea breath testing at least 28 days after treatment confirmed that eradication of H pylori had occurred in no patients. While under treatment, H pylori was sought by conventional methods and by polymerase chain reaction assay and was found in the gastric fundus in 13 of 22 subjects, in the body in 10 of 22, and the antrum in three of 22: the difference between fundus and antrum was significant (p < 0.01). The continued antral infection in three subjects may have resulted from generalised treatment failure as two of three had H pylori detected throughout the stomach, and these two had compiled relatively poorly with treatment. This study suggests that amoxycillin and cimetidine are relatively effective at clearing H pylori from the gastric antrum, but that escape from treatment may occur in the gastric body, and especially the fundus.     

Treatment of Helicobacter pylori in patients with duodenal ulcer hemorrhage--a long-term randomized, controlled study

OBJECTIVE: Eradication of Helicobacter pylori (H. pylori) in patients with uncomplicated duodenal ulcers prevents long-term recurrence of ulcers. We aimed to study whether treatment of H. pylori prevents the long-term recurrence of duodenal ulcer hemorrhage. METHODS: Patients with duodenal ulcer bleeding and confirmed H. pylori infection were recruited. A total of 120 patients were randomly assigned to triple therapy (DeNoltab 120 mg, amoxycillin 500 mg, and metronidazole 300 mg four times daily) or DeNoltab 120 mg four times daily alone. No maintenance therapy was given during the follow-up period. The endpoints were the cumulative rates of symptomatic and bleeding duodenal ulcer recurrences. RESULTS: Of the patients receiving the triple regimen, 85.1% had H. pylori eradicated as compared to 2.0% of patients receiving DeNoltab (p < 0.05). More patients in the DeNoltab group than those in the Triple group had recurrence of ulcer bleeding, but this did not reach statistical significance (12/60 vs 6/60, p = 0.20). Logistic regression analysis on clinical, personal, and endoscopic characteristics identified persistent H. pylori infection as the only independent predictor of recurrence of duodenal ulcer bleeding. CONCLUSIONS: Treatment of H. pylori alone with the present bismuth-based triple therapy in patients with duodenal ulcer hemorrhage did not result in significant reduction in further bleeding episodes, although a trend was seen for the group that was given triple therapy. On the other hand, posttreatment H. pylori status was found to be an independent predictor of bleeding recurrence.     

Comparison of Nizatidine and Cimetidine as Once-Nightly Treatment of Acute Duodenal Ulcer

Nizatidine, a new H2-receptor antagonist for the treatment of duodenal ulcer disease, was compared with cimetidine in an 8-wk, randomized, double-blind, multicenter clinical trial. Patients were randomly allocated to receive either nizatidine 300 mg h.s. or cimetidine 800 mg h.s. Patients were treated for 8 wk, regardless of the healing status of their ulcers. An endoscopy was performed at Wk 2, 4, and 8. Healing rates with nizatidine 300 mg h.s. were numerically, but not statistically significantly, superior to those with cimetidine 800 mg h.s. at each treatment period. Ulcer healing rates at Wk 2, 4, and 8 were 41% (78/191), 73% (130/179), and 81% (145/179) for nizatidine and 33% (60/184), 67% (116/174), and 75% (126/168) for cimetidine, respectively. Symptoms of peptic ulcer disease were similarly reduced at each treatment period by nizatidine and cimetidine. Patients with healed ulcers at either Wk 2 or Wk 4 were continued on therapy and an endoscopy was performed at Wk 8. Ulcer recurrence occurred in 10% of nizatidine-treated and 19% of cimetidine-treated patients at Wk 8 (p = 0.085). The observation of recurrence of duodenal ulcer while patients were receiving full-dose H2-receptor antagonist therapy has not been reported previously.     

The AMOR study: a randomized, double-blinded trial of omeprazole versus ranitidine together with amoxycillin and metronidazole for eradication of Helicobacter pylori.

BACKGROUND: Besides antibiotics, additionally effective acid inhibition is necessary for the eradication of Helicobacter pylori. OBJECTIVE: To assess the significance of acid suppression and, in particular, treatment with proton pump inhibitors (PPIs) compared with H2 receptor antagonists (H2 RAs). The primary target parameter for the study was H. pylori eradication. In addition, the ulcer healing rate, speed of pain reduction, score for gastritis in the antrum and gastric body, and rate of side effects were recorded. DESIGN: Randomized, double-blinded, multicentre study. PARTICIPANTS: A total of 456 patients between the ages of 18 and 80 years with H. pylori-positive duodenal ulcers were included in the study. METHODS: Using a randomization list, patients were assigned either to a treatment group receiving omeprazole 40 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (OAM), or to a group receiving ranitidine 300 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (RAM). The treatment period was 7 days in both groups. Long-term acid-suppressant treatment was not given. RESULTS: The eradication rate was 87.1% (169/194, intention to treat [ITT]) in the OAM group and 77% (137/ 178, ITT) in the RAM group. The difference of 10.1% (95% CI 2.5-18%) is statistically significant (P= 0.0104). The ulcer healing rate was 93.3% in the OAM group (181/194, ITT) and 92.1% in the RAM group (164/178, ITT, NS). With regard to the speed and intensity of pain reduction, the OAM group was superior to the RAM group. In patients in whom H. pylori eradication was successful, the reduction in the antral and gastric body gastritis score was significantly greater than in patients without eradication. In the OAM group, 39.1% of the patients (n = 90) reported one or more side effects, compared with 44.7% (n = 101) in the RAM group (P= 1.5449, NS). CONCLUSION: Omeprazole (40 mg once daily in the morning) is significantly more effective than ranitidine (300 mg once daily in the morning) with respect to H. pylori eradication when used together with amoxycillin (750 mg three times a day) and metronidazole (500 mg three times a day) for a 7-day treatment period.     

Helicobacter pylori Acute Gastritis: Histological, Endoscopical, Clinical, and Therapeutic Features

We describe seven patients with Helicobacter pylori acute gastritis who presented endoscopical picture simulating gastric carcinoma or lymphoma. H. pylori was detected on the antral and on the oxyntic mucosa of all patients. At histological examination, no evidence of malignancy was observed in any of the patients. In the antral mucosa there were edema, hyperemia, and intense polymorphonuclear leukocyte infiltration (neutrophils and some eosinophils) in the lamina propria, mucus layer, and inside the glands. The patients were treated with amoxycillin (2 g/day for 2 months) associated with metronidazole (750 mg/day for 15 days), which reduced the symptoms dramatically. Endoscopy and biopsy, repeated 4 wk after treatment was stopped, showed that the patients had been cleared of H. pylori, and indicated a marked improvement of endoscopical and histological gastritis. These findings indicated that H. pylori acute gastritis can mimic gastric carcinoma or lymphoma. Therefore, histology and detection of H. pylori are essential for an accurate diagnosis.     

Evidence for the essential role of Helicobacter pylori in gastric ulcer disease.

Helicobacter pylori (H pylori) eradication heals chronic active type B gastritis and dramatically changes the natural history of duodenal ulcer disease. There are few data concerning the role of anti-H pylori treatment in gastric ulcer disease. A total of 83 patients presenting with H pylori positive active gastric ulcer disease were treated with omeprazole and antibiotics (amoxicillin, ciprofloxacin, roxithromycin) in seven different clinical protocols, each of which included the attempt to eradicate H pylori infection and to evaluate the post-therapeutic course of ulcer disease. The overall proportion of H pylori eradication was 67.9% (53 of 78 patients available for follow up). Best results were obtained with two week treatment regimens comprising omeprazole 20 mg twice daily and amoxicillin 500 mg four times a day or 1000 mg twice daily (eradication > 80%). Eradication of H pylori speeds up ulcer healing, with a six week healing rate of 84.9% compared with 60% in patients with persistent H pylori infection (p = 0.0148). In a subgroup of 11 patients with refractory ulcers, H pylori eradication (n = 10) was associated with ulcer healing on continued acid suppression in nine cases. One male patient with chronic antral ulcer did not respond to treatment within the next six months (H pylori and ulcer persistence), and in one female patient a resistant body ulcer was identified as gastric lymphoma. Fifty patients with healed ulcers were followed up for one year. Patients with (n = 32) and without (n = 18) bacterial eradication had similar demographic and clinical characteristics. H pylori eradication was associated with a statistically significant reduction of ulcer recurrences (3.1 v 55.6%, p<0.001). This study concludes that H pylori eradication considerably changes the natural history of H pylori associated gastric ulcer disease. In addition, H pylori eradication speeds up ulcers healing and is associated with healing of previously refractory ulcers. Thus, treatment aimed at bacterial eradication should be considered in all patients with gastric ulcers severe enough to contemplate further treatment options.     

Assessment of decisions in the treatment of Helicobacter pylori-related duodenal ulcer: a cost-effectiveness study.

AIMS: Many treatment trials for Helicobacter pylori have been reported but few have evaluated treatment in terms of both cost and effectiveness. It is important to find a therapy with a high eradication rate and low cost, especially in China. The aim of the study is to assess the efficiency of therapy for duodenal ulcers, including ulcer healing, H. pylori eradication and ulcer recurrence. METHODS: Ninety-six consecutive patients with duodenal ulcers and H. pylori infection were randomly allocated into two groups: AMT group (amoxycillin + metronidazole + tagamet); OA group (omeprazole + amoxycillin). Side-effects were recorded during the treatment period. Endoscopic examinations were repeated at the 7th or 8th week to assess ulcer healing. Patients were followed up for 6 months and repeat endoscopy was performed. Ulcer healing rate, H. pylori eradication rate and ulcer recurrence rate were compared. All costs were recorded and a cost-effectiveness analysis was conducted. RESULTS: In the AMT and OA groups, the ulcer healing rate was 83.7 and 93.5%, respectively (P = 0.27). The eradication rate of H. pylori was 65.1 and 69.6%, respectively and was significantly higher in patients with an ulcer diameter < or = 1 cm compared with those with an ulcer diameter > 1 cm, irrespective of treatment group. There was no difference in recurrence rate, duration of pain or the time lost because of the disease. Moderate or severe side-effects were found in 8.9% in AMT group and 6.5% in OA group. The cost of treatment for ulcer healing, H. pylori eradication and reduction in ulcer recurrence were all lower in the AMT group than in the OA group. Sensitivity analysis supported the result that AMT was more cost effective than OA. CONCLUSIONS: The AMT therapy was more effective and less costly than the OA therapy, especially in patients with H. pylori-related duodenal ulcers < 1 cm diameter.     

Recrudescence of Helicobacter pylori Infection in Patients with Healed Duodenal Ulcer after Treatment with Different Regimens

Objective: To determine the 12-month posttherapy recurrence (recrudescence) of Helicobacter pylori in patients with healed duodenal ulcer after apparent eradication of the organism with anti- H. pylori treatment. The influence of original anti- H. pylori treatment regimens on the recrudescence was also evaluated. Methods: One hundred and ninety patients who had duodenal ulcer healed and H. pylori eradicated (as assessed by four routine techniques 4 wk after the end of anti- H. pylori therapy) with one of five regimens were studied. The five regimens were: 1) colloidal bismuth suhcitrate (CBS) 120 mg; 2) CBS plus amoxicillin (500 nig); 3) CBS plus mctronidazole (400 mg); 4) CBS plus metronidazole and amoxicillin; and 5) CBS plus metronidazole and tetracycline (500 mg). CBS was taken four times daily for 4 wk, and antihiotics were taken three times daily for the first week. The patients were re-endoscoped. and the status of H. pylori , duodenal ulcer, and gastritis was assessed after a period of follow-up (mean 14 months after commencement of treatment). Results: H. pylori infection recurred in 36 (18.9%) of these patients. Recrudescence rate with monotherapy was 47.1%, with dual therapy 29.2–35% and with tripie therapy 9.2–14.3%. Nineteen (52.7%) of the 36 patients with recrudescent infection had ulcer relapse, and the rate for H, pylori -negative patients was 3.2% (5/154). Conclusion: Recrudeseence of H. pylori infection after apparent eradication can occur, but it could be that the treatment was only suppressing the organism. The definition of eradication of H. pylori infection may need to he revised, and more sensitive techniques to assess eradication of H. pylori are required.     

Relapse Prevention of Duodenal Ulcers with Trimipramine,Cimetidine, or Placebo

In a double-blind study 83 patients with duodenal ulcers, initially healed after treatment with either 1 g cimetidine daily or 50 mg trimipramine daily, were allocated by randomization to maintenance treatment with either 400 mg cimetidine daily, 25 mg trimipramine daily, or placebo for 6 months. Monthly clinical interviews were carried out and endoscopy performed whenever the symptoms suggested ulcer relapse. After 6 months the treatment was discontinued, and the patients were observed similarly for another 6-month period. After 6 months of maintenance treatment 88% in the cimetidine group versus 55% in the trimipramine group and 53% in the placebo group remained in symptomatic remission, yielding a significant difference between the cimetidine-treated patients and the two other groups (P < 0.05). After a further 6 months of drug-free follow-up study, the percentages were 48% versus 29% and 29% in the cimetidine, trimipramine, and placebo groups, respectively (P < 0.05). Thus maintenance treatment with trimipramine proved no better than placebo in preventing relapses of duodenal ulcers. Second, maintenance treatment with 400 mg cimetidine daily did prevent ulcer relapse, and, third, maintenance treatment with cimetidine for 6 months did not alter the long-term course of the duodenal ulcer disease.     

Helicobacter pylori and Duodenal Ulcer Recurrence

Preliminary evidence suggests that eradication of Helicobacter pylori (H. pylori) may lead to prolonged remission of duodenal ulcer (DU). The aim of this study was to assess the long-term effect of eradication of H. pylori on the natural history of DU. Fifty-one patients with endoscopically proven duodenal ulcers, who were found to have H. pylori infection on histology and culture, and who were successfully eradicated of H. pylori with combination treatment of colloidal bismuth subcitrate and antibiotics, were studied. All patients were endoscoped at entry, 4 wk after cessation of treatment and again at 1 yr or sooner, if symptoms recurred. At each endoscopy, two antral biopsies were taken and assessed histologically and microbiologically for evidence of H. pylori infection. Recurrence of H. pylori infection occurred in 18/51 patients (35.3%) and, of these, 12 patients had evidence of recurrent peptic disease (five DU, seven duodenitis). In contrast, of the 33 who remained negative for H. pylori at 1 yr, none developed evidence of recurrent DU. Overall, DU recurrence occurred in 5/51 patients (11.7%), and occurred only in patients reinfected with H. pylori. This relapse rate compares favorably with patients on maintenance H2-receptor antagonist treatment. These results lend further support to the hypothesis that antral reinfection with H. pylori is associated with relapse of DU.     

Ranitidine bismuth citrate-based triple therapy for seven days, with or without further anti-secretory therapy, is highly effective in patients with duodenal ulcer and Helicobacter pylori infection

OBJECTIVE: To compare the efficacy of two protocols for the eradication of Helicobacter pylori infection and the healing of active duodenal ulcer: (i) ranitidine bismuth citrate (RBC) plus two antibiotics for 7 days, and (ii) the same triple therapy followed by 3 weeks of anti-secretory drug treatment. METHODS: The study comprised 102 patients with active duodenal ulcer and H. pylori infection; the patients were randomized to open treatment with either RBC 400 mg b.d. plus amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 7 days, or the same treatment followed by 3 weeks of RBC 400 mg b.d. alone. Ulcer healing was confirmed by endoscopy. H. pylori eradication was assessed by endoscopy, rapid urease test and histology. RESULTS: The ulcer healed in 48/50 patients on RBC-based triple therapy alone (96.0%) and in 51/52 patients on triple therapy plus further anti-secretory treatment (98.1%). On an intention-to-treat basis, H. pylori had been successfully eradicated in 42/50 patients on triple therapy (84.0%) and in 44/52 patients on triple therapy plus anti-secretory treatment (84.6%), while by per protocol analysis the H. pylori eradication rates were 91.3% (42/46) and 89.8% (44/49), respectively. CONCLUSIONS: One-week triple therapy with RBC, amoxycillin and clarithromycin is highly effective in eradicating H. pylori and healing duodenal ulcers, even if not followed by anti-secretory drug treatment.     

Effect of Cimetidine on Gastric Mucosal Cell Proliferation in Man

Seven duodenal ulcer patients were treated for 3 months with cimetidine. Before and after treatment endoscopic biopsy specimens were taken for autoradiographic estimation of cell proliferation in the gastric mucosa in the antral and fundic part of the stomach and from the duodenum. In all three areas the estimated labeling index was increased during medication with cimetidine. The increase in epithelial cell renewal may participate in the ulcer healing effect of cimetidine.     

Clinical Utility and Cost Effectiveness of Helicobacter pylori Testing for Patients with Duodenal and Gastric Ulcers

Objective: Current consensus guidelines recommend that all patients demonstrating either a gastric or duodenal ulcer he tested for Helicobacter pylori , the most common cause of ulcers. We determined the clinical utility and cost effectiveness of H. pylori testing in patients with duodenal and gastric ulcers. Methods: A retrospective evaluation and cost-effectiveness analysis of 565 consecutive patients with endoscopically demonstrated gastric or duodenal ulcers over a 4-yr period in a large, urban general hospital. The main outcome variables are the percentage of patients who had a gastric biopsy, the prevalence of H. pylori , and the cost effectiveness of testing (antral biopsy, CLO test, serum antibody, and urea breath test) for H. pylori. Results: Significantly more patients with endoscopically documented duodenal ulcers had an antral biopsy performed in 1993 and 1994 when compared with patients from 1991 and 1992 (p < 0.00001). For patients with gastric ulcers, biopsies were performed at a similar rate throughout this study. Overall, patients with duodenal and gastric ulcers demonstrated H. pylori 75% and 69% of the time, respectively. The total charges for biopsy documentation and treatment of H. pylori in all duodenal ulcer patients in this cohort was estimated at $25,135. If a biopsy for H. pylori had been performed in all patients the actual charges would have been $77,443. Conversely, charges would have been only $8085 had all patients been empirically treated for H. pylori based on the high pretest probability of infection. Conclusions: Routine testing for H. pylori is very expensive, regardless of the diagnostic method used. Biopsy results do not provide clinically useful information in most patients with duodenal ulcers and may be misleading if falsely negative.     

Does treatment of Helicobacter pylori with antibiotics alone heal duodenal ulcer? A randomised double blind placebo controlled study.

BACKGROUND: Treatment of Helicobacter pylori infection prevents duodenal ulcer relapse. It has not been established if treatment of the infection heals duodenal ulcer. AIM: To test the hypothesis that treatment of the infection was associated with healing of duodenal ulcer. METHODS: A randomised, double blind placebo controlled trial was performed to study the efficacy of an antibiotic only regimen consisting of 300 mg metronidazole, 500 mg amoxycillin, and 250 mg clarithromycin, each given four times daily for two weeks, in the healing of duodenal ulcer as assessed by endoscopy. Symptoms were controlled with acetaminophen and antacids. RESULTS: Of 100 consecutive patients with endoscopically established duodenal ulcer, 97 with positive rapid urease test on antral biopsy specimens were admitted into the study and 81 completed the trial. Of these, 40 were randomised to receive antibiotics and 41 to receive placebo. Treatment with antibiotics resulted in 92.5% (95% confidence interval (95% CI) 84.3-100) healing at four weeks and 100% at eight and 12 weeks; the corresponding healing rates for placebo treatment were respectively, 36.6%, 61%, and 63.4% (95% CIs 21.8-51.3, 46.0-75.9, and 48.7-78.2 respectively). The differences between the two treatment groups were significant at p < 0.001 at each time point and by life table analysis. Clearance of H pylori as assessed by urease test on antral biopsy specimens at four weeks and eradication of the organism as determined by 13C-urea breath test at eight weeks were achieved in 85% and 62.5% of patients respectively. Duodenal ulcer healed at four weeks in 87.2% and 86.2% (95% CIs 76.7-97.7 and 73.7-98.8) of patients in whom H pylori clearance or eradication, was achieved, versus 42.9% and 51.9% (95% CIs 27.9-57.8 and 38.3-65.5; p < 0.001 and < 0.003 respectively) in whom these processes failed. Stepwise discriminant analysis on 32 clinical, personal, and endoscopic characteristics as well as H pylori clearance and eradication identified H pylori clearance as the most discriminative variable for the healing of duodenal ulcer at four weeks, followed by ulcer depth and eradication of the organism. CONCLUSIONS: Treatment with an antibiotic only regimen was effective for the healing of duodenal ulcer, and clearance as well as eradication of H pylori contributed significantly to the healing. The results constituted the strongest evidence to date that H pylori infection was aetiologically related to duodenal ulceration, and support the concept of treating duodenal ulcer associated with H pylori as an infection and relieving its symptoms with acid reducing agents such as antacids.     

Restorative proctocolectomy and pouch anal anastomosis for ulcerative colitis following orthotopic liver transplantation.

This study tested the influence of pretreatment bacterial density on the eradication rate of Helicobacter pylori with triple therapy. One hundred and thirty two patients with endoscopically confirmed H pylori positive, duodenal ulcer or antral gastritis were treated with triple therapy (colloidal bismuth/metronidazole/amoxicillin) for two weeks. Pretreatment urease activity was assessed by the 14C-urea breath test (UBT) in all patients. The mean (SD) pretreatment UBT concentration was similar in patients with duodenal ulcers (318.4 (175.0)) and patients with antral gastritis (288.9 (165.5)). Overall eradication of H pylori was achieved in 85 of 132 patients (64.4%), but was significantly different between patients with high, intermediate, or low pretreatment urease activity (37.5%, 69.5%, and 87.8% respectively). The mean post-treatment UBT value of patients in whom eradication failed was in direct correlation with the pretreatment UBT values. In conclusion, bacterial density, as assessed by urease activity, is an important factor in predicting H pylori eradication. It is suggested that the pretreatment UBT has the potential to identify patients who require modification of the standard therapeutic regimen.     

Eradication of Helicobacter pylori with clarithromycin and omeprazole.

Clarithromycin, a new and well tolerated, acid stable macrolide antibiotic, has a similar antimicrobial spectrum to erythromycin but a better in vitro MIC90 (0.03 microgram/l-1) against Helicobacter pylori (H pylori). This study aimed at determining the eradication rate using clarithromycin 500 mg thrice daily and omeprazole 40 mg daily for two weeks. Patients were given an endoscopy and H pylori status assessed by antral culture (microaerobic conditions, for up to 10 days), antral and corpus histology tests (haematoxylin and eosin/Gimenez stains), and 13C-urea breath test (13C-UBT, European standard protocol, positive result = excess delta 13CO2 excretion > 5 per mil). Compliance was assessed by returned tablet counts. H pylori clearance at the end of treatment and eradication four weeks after finishing treatment were assessed by the 13C-UBT. Seventy three patients (54 men, median age 45 years) with duodenal ulcers (n = 42) or duodenitis/non-ulcer dyspepsia (n = 31) all with a positive 13C-UBT (mean (SEM) excess delta-13CO2 excretion = 26.6 (4.9) per mil) and either positive antral histology (n = 72) or positive antral culture (n = 35) were studied. Before treatment 2/27 (7%) isolates of H pylori were resistant to clarithromycin and five isolates were resistant to metronidazole. In 70/73 (96%) the 13C-UBT was negative immediately after finishing treatment. Four weeks later the 13C-UBT was negative in 57/73 (mean (SEM) excess delta 13CO2 excretion = 1.2 (0.3) per mil, eradication rate = 78%). Forty eight (66%) patients experienced a metallic taste while taking the tablets. Although four (5%) patients, however, could not complete the course of treatment, in only one of these four was H pylori not eradicated. These results show that duel therapy with clarithromycin and omeprazole is well tolerated. With an eradication rate of 78% it is an effective treatment for metronidazole resistant H pylori and may be an alternative to standard triple therapy.