Azithromycin for the cure of Helicobacter pylori infection.

OBJECTIVES: Azithromycin, a new antibiotic chemically related to erythromycin, has been proposed for the cure of Helicobacter pylori, achieving high gastric tissue levels (above the MIC for H. pylori) after oral administration. The aim of the study was to establish whether azithromycin plus metronidazole in association with either omeprazole or bismuth subcitrate is useful in curing H. pylori infection of the stomach. PATIENTS AND METHODS: The study involved 132 dispeptic patients who proved to be H. pylori infected by antral and corpus histology (Giemsa, modified) and rapid urease test (CLOtest); the Sydney system was used to classify the gastritis. Sixty-three patients received bismuth subcitrate 120 mg q.i.d. for 14 days plus azithromycin 500 mg o.d. for the first 3 days plus metronidazole 250 mg q.i.d. for the first 7 days; 69 patients received omeprazole 40 mg for 14 days plus azithromycin 500 mg o.d. for the first 3 days plus metronidazole 250 mg q.i.d. for the first 7 days. Patients were well matched for common clinical variables. Cure of H. pylori infection was assessed by the same methods 2 months after completion of treatment. RESULTS: Eleven patients dropped out of the study, only one reporting side effects (nausea, vomiting, and epigastric pain). Cumulative "per protocol" cure rate was 66.1% (CI 95%, 58.5-75.3%). There was no statistically significant difference between the two treatment groups: 58.9% (CI 95% 48.4-74.6%) versus 72.3% (CI 95%, 60.7-82.5%). Intention to treat does not substantially modify results. Few side effects were recorded. Cured patients showed a significant reduction in the activity of gastritis. CONCLUSION: Azithromycin, combined with omeprazole and metronidazole, the cure rate of H. pylori was about 70%. The cure of H. pylori infection improves the activity of gastritis.

Absence of tolerance in duodenal ulcer patients treated for 28 days with a bedtime dose of roxatidine or ranitidine.

There is much experimental work on the occurrence of tolerance to the antisecretory effect of H2-receptor antagonists in healthy subjects, while data on its development in patients with duodenal ulcer are poor and conflicting. Moreover, this phenomenon has not been studied previously with 24 h gastric pH-metry in patients with active duodenal ulcer. For these reasons, we carried out a prospective pharmacodynamic investigation in 48 patients with endoscopically proven duodenal ulcer using the well-established once daily dosing schedule of H2 blockers. They were studied by means of 24 h continuous endoluminal pH-metry which was performed before, on d1 and d28 after receiving an oral bedtime dose (2200 hours) of either roxatidine 150 mg or ranitidine 300 mg, given in randomized and single-blind fashion. Eight patients did not complete the study for various reasons and 82% of ulcers healed after 4 weeks of therapy. Gastric pH was higher (P < 0.001) on d1 and d28 than basal values during all time periods, but the evening, with both H2 blockers. There was no significant difference between pH values of d1 and d28 in any time interval with both roxatidine and ranitidine. There was also no difference in pharmacodynamic data between the two active treatments. We conclude that tolerance does not develop after 1 month's treatment with a bedtime dose of H2 antagonist in patients with active duodenal ulcer and therefore data gathered on this phenomenon in healthy subjects are not applicable to ulcer patients.

Do concomitant diseases and therapies affect the persistence of ulcer symptoms in the elderly?

Risk factors of slow healing were previously researched in a large sample of duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence of ulcer symptoms was proven the most reliable factor in predicting nonhealing ulcer, while ulcer size was of importance only for DU. We aimed to complete the analysis, with a more careful evaluation of concomitant diseases and therapies. Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU patients. Ninety-three patients dropped out of the study; 79/294 gastric ulcers and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular, gastrointestinal, and pulmonary disorders were the most frequent concomitant diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients. Ulcer healing was the major determinant of persistence of ulcer symptoms; esophagitis emerged as an important adjunctive and independent factor. Use of hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a role. With persistence of ulcer symptoms removed from the analysis, ulcer size was the most constant factor affecting ulcer healing. NSAID use, cardiovascular disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major indicator of slow ulcer healing in the elderly, is independently affected also by the presence of esophagitis. Use of hypoglycemic agents and smoking habit may also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which the most constant indicators remained persistence of ulcer symptoms and ulcer size.

Risk factors of duodenal ulcer bleeding: the role of smoking and nicotine.

Several studies have shown that cigarette smoking affects duodenal ulcer (DU) recurrence. To verify any correlation between smoking and complications of ulcer disease, we studied 33 DU smokers, 16 DU ex-smokers and 87 DU non-smokers for up to 48 months, recording age, sex, family history of ulcer, ulcer symptoms, non-steroidal anti-inflammatory drug use, length of DU history, alcohol consumption, smoking habit, relapses and bleeding episodes. Nicotine contents were also obtained for the type of cigarettes smoked. Statistics used were: Analysis of variance with Bonferroni's test. Pearson's chi-squared test and stepwise logistic regression analysis. Smokers were found to have significantly more relapses but fewer bleeding episodes than ex-smokers and non-smokers (63.3%, 31.2% and 34.5%, p = 0.029; 12.1%, 43.7% and 34.5%, p = 0.017). Bleeders were significantly more often males than non-bleeders (82.9% vs. 61.0%, p = 0.01) and had ulcer symptoms less frequently (9.7% vs. 26.3%, p = 0.02). Multivariate analysis confirmed sex as a risk factor (OR = 3.0) and smoking as a "protective" factor (OR = 0.4) for bleeding, while nicotine intake was found to be unrelated to this complication. We concluded that smoking (but not nicotine intake) and male sex are factors to take into account in evaluating the risk of DU bleeding.

Compliance with therapy for ulcer disease: clinical experience and review of the literature.

As a factor favoring relapses, noncompliance is particularly crucial to the treatment of peptic ulcer disease, and greater efforts should be made to eliminate or reduce it. To investigate the reasons for noncompliance, we performed two clinical trials involving a total of 592 patients with duodenal ulcer treated with various H 2 antagonists for 12 months. In the first study, 40.3% of patients with uncomplicated duodenal ulcer were noncompliant, compared with only 4.6% who had had previous bleeding episodes. Compliance in the second study averaged 68%. Major reasons for noncompliance among these patients were an absence of symptoms and an inconvenient dosage schedule. On the basis of our clinical experience and a review of the literature, compliance appears to be higher in patients with previous complications of their disease and when the effectiveness of prescribed drugs does not depend on ingestion with the evening meal.

Markers of slow-healing peptic ulcer in the elderly. A study on 1,052 ranitidine-treated patients.

Little is known about ulcer outcome in the elderly. The aims of the present paper were to establish whether risk factors of slow-healing peptic ulcer can be demonstrated in the elderly and whether clinical differences exist between ulcer patients whose age of onset of the disease was before or after 65 years old. The short-term, open study, involving 1052 elderly patients (over 65 years) in 37 gastroenterology centers throughout Italy aimed to compare two schedules of ranitidine treatment: 150 mg twice daily versus 300 mg at bedtime. As nonsignificant differences were found between these two schedules, the sample was considered as a whole. It included 319 gastric ulcer (GU) patients, 699 duodenal ulcer (DU) patients, and 34 concomitant GU and DU cases. Ninety-three patients dropped out of the trial; 79/294 GU, 138/635 DU, and 10/30 GU+DU were found still unhealed after four weeks and 20 GU, 15 DU, and 1 GU+DU remained so after eight weeks. Statistical analysis was performed using likelihood-ratio and Pearson's chi-squared tests and Cox's models. Univariate analysis showed that the indicators of slow-healing GU were ulcer size (P = 0.002) and persisting ulcer symptoms (P = 0.0001); indicators of slow-healing DU were ulcer size (P = 0.0001), persisting ulcer symptoms (P = 0.0001), alcohol (P = 0.0003), and NSAID (P = 0.0088) consumption. DU patients taking antiplatelet drugs have significantly better results after four weeks and worse results after eight weeks (P = 0.0352).(ABSTRACT TRUNCATED AT 250 WORDS)