The discovery several decades ago of the infection of the gastric mucosa with Helicobacter pylori (H. pylori), and its association with chronic antral gastritis and peptic gastroduodenal ulcer, has revolutionized the treatment of ulcer illness in recent years. Even though the pathogenesis of this germ in ulcer illness is not yet clear, there are facts that justify the application of an antibiotic therapy, such as reduction of the ulcer recurrence after treatment. H. pylori has been isolated at the gastric antral level in 90% of patients with duodenal ulcer and in 70% of patients with gastric ulcer.

Multiple treatment schemes have been used, to which different degrees of eradication of the H. pylori have corresponded, but the optimal therapeutic regime has not yet been established. Location of the bacteria underneath the mucosal surface that covers the gastric epithelium, the acid environment of the stomach and bacterial resistance, among other factors, all contribute to the difficulties of eradication.

The best results in relation to eradication of the H. pylori have been obtained with the administration of several drugs, using dual or triple therapy. Among the most employed antimicrobial drugs with this goal are amoxicillin, tetracycline, clarithromycin, the nitroimidazoles, and those composed of bismuth, whether or not associated with inhibitors of acid secretion.

The colloidal bismuth subcitrate (CBS) formulated, patented and registered in Cuba under the name of Q-ULCER, in addition to its antibacterial action on the H. pylori, has an effective healing action in gastroduodenal ulcers and is used in a monotherapy treatment. A recent study performed by these authors has shown a 68% reduction of the germ. The administration of CBS has been recommended in association with metronidazole and tetracycline or amoxicillin as a therapy for the eradication of the H. pylori, with positive results of approximately 90%.

The purpose of this work is to compare the possible efficiency of these two triple therapies (CBS + metronidazole + tetracycline and CBS + metronidazole + amoxicillin) with the monotherapy treatment based on CBS only, in relation to the healing of ulcer diagnosed by endoscopy and the reduction and eradication of the germ, through the evaluation of the three treatment schemes in patients with gastroduodenal ulcer with H. pylori.

Materials and Methods

Sample selection

Sixty patients of both genders, who previously gave consent to participate in this study, were selected from the gastroenterology service. All had duodenoscopy for presenting ulcer syndrome and endoscopic diagnosis was peptic or duodenal ulcer with positive H. pylori by urease test. Subjects were randomly distributed into three groups of 20 patients each.

Materials

The endoscopies were performed using EVIS-100 (Olympus) videoendoscopy. In each case three biopsy samples were taken from the gastric antral with previously sterilized nippers. One of the samples was submitted to a urease test with Urepyl-L reactive produced in Cuba. The other two were used in a morphologic and histologic study of the germ with hematoxylin and eosin and Warthin Starry techniques. In order to evaluate H. pylori eradication, the endoscopies were made before treatment, at the end of treatment, and 1 month later in patients that presented reduction of the germ.

A thorough clinical history, as well as clinical symptoms, was obtained from subjects before treatment, at the fourth week of treatment and at the end of treatment. Additionally, negative and collateral effects were gathered. A patient was considered asymptomatic at the end of treatment if he/she reported a total disappearance of the initial symptoms and improved when reporting a reduction of the initial symptoms >50%.

The following terms were considered: healing, when there was a complete disappearance of the ulcer lesion diagnosed by endoscopy at the end of the treatment; reduction and eradication, when a negative H. pylori was obtained at the end of the treatment and 1 month later, respectively, using the two diagnostic methods mentioned. The urease test was considered negative if no color change was observed in the reactive in 24 h and positive if the reactive showed a pink or light purple color before 24 h. The histological detection of the germ throughout the techniques described previously allows the determination of its presence or absence in the samples examined.

Inclusion criteria

Those subjects included were patients with gastric or duodenal ulcer, unique or double, uncomplicated, diagnosed endoscopically with positive H. pylori by urease test, and willing to adhere to the drug therapy as prescribed. These patients were given strict warnings not to take any other antiulcer medicine during this treatment. Pregnant patients, as well as those who presented allergic symptoms or known intolerance to some of the drugs that were going to be supplied or ones that were already under AINE medication for other pathologies without being able to suspend it, were excluded.

Final sample

From the 60 patients included in the initial random samples, 53 formed part of the final sample, seven were dropouts because they did not submit to the necessary endoscopies. The groups were finally formed by the following: group I: 17 patients; group II: 17 patients; and group III: 19 patients. Of these, 40 were male (75.5%) and 13 females (24.5%) with an average age of 43 years.

Results

Before treatment, the clinical symptoms most frequently reported by the patients were epigastric pain (92.4%) and acidity (81.1%). At the end of treatment, 9 patients from group I were found asymptomatic, 10 from group II and 13 from group III. The remaining patients reported as improved. No significant differences (p >0.05) were found in the reduction of the symptoms for the three treatment schemes. Regarding the negative reactions, in group I, 17.6% of the patients reported constipation during treatment. In group II, 29.4% of the patients reported nausea (three patients) and cutaneous rash (two patients), and in group III, 31.5% presented negative effects (three with stomatitis, two with nausea and one with constipation). All effects were minimal, so there was no need to discontinue treatment.

In the initial duodenoscopy, 45 patients presented duodenal ulcer, distributed by the three groups as follows: 15, 14, and 16 correspondingly. Eight had gastric ulcer (two in group I, and three each in groups II and III). At the end of treatment, the ulcers had healed in 12 patients (70.5%) from group I, in 14 patients (82.3%) from group II and in 15 patients (78.2%) from group III. These values, although slightly higher in groups II and III, did not present significant differences (p >0.05) among the three treatment schemes used.At the beginning of treatment, 100% of the patients presented a positive H. pylori detected by the two methods previously mentioned, but at the end many of the patients in whom urease test had proved negative (Hp-), the histological detection proved positive).