tetracycline and bismuth-subsalicylate

As one of the most prevalent infections globally, Helicobacter pylori (H. pylori) continues to present diagnostic and therapeutic challenges for clinicians worldwide. Diagnostically, the "test-and-treat" strategy is the recommended approach for healthcare practitioners when managing this potentially curable disease. The choice of testing method should be based on several factors including patient age, presenting symptoms, and medication use, as well as test reliability, availability, and cost. With rising antibiotic resistance, particularly of macrolides, care must be taken to ensure that therapy is selected based on regional resistance patterns and prior antibiotic exposure. In the USA, macrolide antibiotic resistance rates in some areas have reached or exceeded a generally accepted threshold, such that clarithromycin triple therapy may no longer be an appropriate first-line empiric treatment. Instead, bismuth quadruple therapy should be considered, while levofloxacin-based or alternative macrolide-containing therapies are also options. Once treated, it is essential to test for eradication as untreated H. pylori is associated with serious complications including peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. This review article aims to consolidate current knowledge of H. pylori infection with a particular emphasis on diagnostic and treatment strategies.

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Antigens, Bacterial; Biopsy; Bismuth; Breath Tests; Clarithromycin; Culture Techniques; Doxycycline; Drug Resistance, Bacterial; Drug Therapy, Combination; Dyspepsia; Feces; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Levofloxacin; Lymphoma, B-Cell, Marginal Zone; Metronidazole; Nitro Compounds; Organometallic Compounds; Peptic Ulcer; Polymerase Chain Reaction; Proton Pump Inhibitors; Rifabutin; Salicylates; Salvage Therapy; Serologic Tests; Stomach Neoplasms; Tetracycline; Thiazoles; Treatment Outcome; Urea

National Danish guidelines for the diagnosis and treatment of Helicobacter pylori (Hp) infection have been approved by the Danish Society for Gastroenterology. All patients with peptic ulcer disease, gastric cancer, and MALT lymphoma should be tested for Hp. We also recommend testing in first degree relatives to patients with gastric cancer, in NSAID-naive patients, who need long-term NSAID therapy, and in patients presenting with dyspepsia and no alarm symptoms. Non-endoscoped patients can be tested with a urea-breath test or a faecal antigen test. Endoscoped patients can be tested with a rapid urease test. Proton pump inhibitor therapy should be stopped at least 1 week prior to Hp testing. All infected patients should be offered Hp eradication therapy. First-line treatment is 7-day triple therapy with a proton pump inhibitor and clarithromycine in combination with metronidazole or amoxicilline. Quadruple therapy for 2 weeks with bismuthsubsalicylate, tetracycline, metronidazole and a proton pump inhibitor is recommended in case of treatment failure. Hp testing should be offered to all patients after eradication therapy but is mandatory in patients with ulcer disease, noninvasive gastric cancer or MALT lymphoma. Testing after eradication should not be done before 4 weeks after treatment has ended.

Topics: Amoxicillin; Anti-Bacterial Agents; Antidiarrheals; Bismuth; Clarithromycin; Denmark; Drug Therapy, Combination; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans; Lymphoma, B-Cell, Marginal Zone; Metronidazole; Organometallic Compounds; Peptic Ulcer; Proton Pump Inhibitors; Salicylates; Stomach Neoplasms; Tetracycline

Topics: Amoxicillin; Bismuth; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Salicylates; Tetracycline

Patients with Helicobacter pylori-induced duodenal ulcer should have their infection eradicated. The optimal choice of antibiotic therapy, however, is less clear.. To evaluate costs and outcomes of treatment with 8 antibiotic regimens with documented activity against H pylori vs maintenance therapy with histamine2-receptor antagonists (H2RA).. A meta-analysis for 119 studies enrolling 6416 patients to determine aggregate eradication rates. The complexity of each regimen was used to determine the anticipated compliance rate and actual effectiveness. A decision analytic model with Monte Carlo simulation determined annual costs and health outcomes.. Average annual total costs of testing for H pylori infection and antibiotic treatment ranged from $223 to $410 and prevented ulcer recurrence in 70% to 86% of patients. The H2RA maintenance therapy cost $425 and prevented recurrence in 72% of patients. The lowest costs and recurrence rates were achieved by 3 regimens: standard triple therapy (a combination of bismuth subsalicylate, metronidazole, and tetracycline hydrochloride) for 14 days ($223, with 18% recurrence); a combination of clarithromycin, metronidazole, and a proton pump inhibitor for 7 days ($235, with 15% recurrence); and standard triple therapy with a proton pump inhibitor for 7 days ($236, with 14% recurrence).. Treatment with any regimen resulted in lower costs compared with H2RA maintenance therapy. Three antibiotic regimens had consistently lower costs and better outcomes: standard triple therapy for 14 days, metronidazole, clarithromycin, and a proton pump inhibitor for 7 days, and standard triple therapy plus a proton pump inhibitor for 7 days.

Topics: Anti-Bacterial Agents; Bismuth; Clarithromycin; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Monte Carlo Method; Organometallic Compounds; Patient Compliance; Proton Pump Inhibitors; Recurrence; Salicylates; Tetracycline; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Salicylates; Tetracycline

Peptic ulcer disease is strongly associated with infection by Helicobacter pylori, a spiral-shaped, flagellated organism found predominantly in the gastric antrum. More than 90 percent of duodenal ulcers and adenocarcinomas of the distal stomach are associated with H. pylori infection. Eradication of the organism effectively prevents relapses of gastroduodenal ulcers associated with H. pylori. In patients undergoing endoscopy, the rapid urease test is highly sensitive and specific in diagnosing H. pylori infection. Noninvasive diagnostic methods include serologic antibody measurements and urea breath testing. Empiric therapy may be tried if the diagnosis is suspected on a clinical basis. Traditional 14-day "triple therapy" with bismuth, metronidazole and either amoxicillin or tetracycline has consistently produced eradication rates of approximately 90 percent. Newer combination regimens have shown promise in a smaller number of studies. No single agent given as monotherapy has proved to be acceptably effective in clinical studies.

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Organometallic Compounds; Penicillins; Peptic Ulcer; Protein Synthesis Inhibitors; Salicylates; Tetracycline

Topics: Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Gastric Acid; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metronidazole; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline

Topics: Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline; United States

The aim of this study was to compare the efficacy and safety of 2-week levofloxacin-containing triple therapy, levofloxacin-containing bismuth quadruple therapy, and standard bismuth-containing quadruple therapy as a first-line regimen for the eradication of Helicobacter pylori.. A total of 329 patients with H. pylori infection were randomly divided into 3 groups to receive one of the following regimens: (a) levofloxacin-containing bismuth quadruple therapy, RBAL (rabeprazole 20 mg, b.i.d., bismuth subsalicylate 562 mg, b.i.d., amoxicillin 1 g, b.i.d, levofloxacin 500 mg, once daily), (b) standard bismuth quadruple therapy, RBMT (rabeprazole 20 mg, b.i.d, subsalicylate 562 mg, b.i.d., metronidazole 500 mg, t.i.d, tetracycline 500 mg, q.i.d), or (c) levofloxacin-containing triple therapy, RAL (rabeprazole 20 mg, b.i.d., amoxicillin 1 g, b.i.d, levofloxacin 500 mg, once daily). The primary outcome was the eradication rate in the intention-to-treat (ITT) and per protocol (PP) analysis.. The eradication rates of the above 3 groups using ITT analysis were RBAL 83.8%, RBMT 88.3%, and RAL 74.8% compared with 91.2, 92.5, and 79.2%, respectively, using PP analysis. The eradication rate using RBMT was significantly higher than that of RAL (p = 0.029 in ITT analysis and p = 0.017 in PP analysis). Several side effects occurred in 156 patients (54.1%) in the RBAL group, 215 (52.3%) in the RBMT group, and 56 (26.2%) in the RAL group (p > 0.05, RBAL vs. RBMT; p < 0.001, RBMT vs. RAL; p < 0.001, RBAL vs. RAL).. All bismuth-containing quadruple therapies had acceptable eradication rates, but levofloxacin-containing triple therapy was not as good as quadruple therapies. Hence, quadruple therapies should be considered the preferred first-line therapy for H. pylori infections.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Helicobacter Infections; Humans; Levofloxacin; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Tetracycline; Young Adult

Helicobacter pylori eradication rates with standard triple regimens are worsening, and alternative treatments are urgently needed in some populations. The present study aimed to compare the efficacy of bismuth-based quadruple and concomitant regimens.. Consecutive Helicobacter pylori-positive patients with non-ulcer dyspepsia were randomized to receive one of two regimens: (i) bismuth subsalicylate 300 mg q.i.d., esomeprazole 40 mg b.i.d., tetracycline 500 mg q.i.d., and amoxicillin 1 g b.i.d. (bismuth group) or (ii) esomeprazole 40 mg b.i.d., tetracycline 500 mg q.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg t.i.d. (concomitant group) for 14 days. Gastroscopy and 14C-urea breath test were performed before enrollment, and urea breath test was repeated six weeks after the treatment.. A total of 200 patients were randomized, and 180 of them completed the protocols. The intention-to-treat and per-protocol eradication rates were 79% (95% confidence interval 71-87) and 89.7% (95% confidence interval 83-95) in the bismuth group and 74% (95% confidence interval 68-81) and 80.4% (95% confidence interval 72-87) in the concomitant group. The bismuth regimen achieved a slightly better eradication rate compared to the concomitant group in both per-protocol and intention-to-treat analysis, but results were not statistically significant (p>0.05). Ten patients (6 in bismuth, 4 in concomitant groups) dropped out of the study because of side effects.. The quadruple regimens with or without bismuth achieved moderate eradication rates as a first-line eradication option of Helicobacter pylori in our population, in which a bismuth-based regimen seems more appropriate. The compliance and side effects are important issues affecting the success of these regimens.

Topics: Adolescent; Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Ulcer Agents; Antidiarrheals; Bismuth; Drug Therapy, Combination; Esomeprazole; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Prospective Studies; Salicylates; Tetracycline; Young Adult

Quadruple therapy provided inadequate eradication rate when given twice-a-day at breakfast and evening meals.. To test twice daily (mid-day and evening) quadruple therapy for Helicobacter pylori eradication.. This was a single-centre pilot study in which H. pylori-infected (positive histology and culture and RUT) patients were given 2 x 250 mg of metronidazole and 2 x 250 mg of tetracycline, two Pepto-Bismol tablets, plus one 20 mg rabeprazole tablet twice-a-day for 14 days. H. pylori status was confirmed 4 or more weeks after the end of therapy.. Thirty-seven patients including 3 with peptic ulcer disease, 19 asymptomatic infected, 4 GERD, and 11 with NUD. Mid-day quadruple therapy was successful in 92.3% (95% CI: 79-98%) including 96.2% of those with metronidazole-susceptible strains, and in 83.3% (10/12) of those with metronidazole-resistant H. pylori. Compliance was 100% by pill count except in one individual who stopped medication after 12 days because of side-effects and who failed therapy. Moderate or greater side-effects were experienced by five patients.. Twice-a-day, mid-day, quadruple therapy proved effective using the combination of bismuth subsalicylate and rabeprazole instead of bismuth subcitrate and omeprazole. Detailed studies of different formulations (e.g. 2 x 250 mg versus 1 x 500 mg of metronidazole or tetracycline) and timing of administration (breakfast and evening meal versus mid-day and evening meals) may result in significant improvements in H. pylori eradication regimens.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Antacids; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Ulcer Agents; Benzimidazoles; Bismuth; Drug Administration Schedule; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Patient Compliance; Pilot Projects; Prospective Studies; Proton-Translocating ATPases; Rabeprazole; Salicylates; Tetracycline; Treatment Outcome

We used data from a randomized placebo-controlled clinical trial to examine the relationship between Helicobacter pylori and reflux symptoms in nonulcer dyspepsia patients randomly assigned anti-Helicobacter pylori triple therapy alone, calcium carbonate alone, or in combination with triple therapy, tetracycline, or placebo. We compared risk differences for posttreatment Helicobacter pylori status and increased reflux symptoms from crude, multivariable and stratified multivariable analyses. In crude analyses, 54% of subjects without Helicobacter pylori after-treatment reported an increase in reflux compared to 41% of those with persistent infection (risk difference = 13%; P = 0.07). Only subjects with multifocal atrophic gastritis assigned to calcium carbonate reported an increase in reflux symptoms more frequently when Helicobacter pylori was absent versus when it persisted (risk difference = 52%; P = 0.0001). Therefore, the interaction of calcium carbonate use, chronic multifocal atrophic gastritis, and the absence of Helicobacter pylori may increase reflux symptoms.

Topics: Adult; Amoxicillin; Antacids; Bismuth; Calcium Carbonate; Drug Therapy, Combination; Dyspepsia; Female; Gastric Acidity Determination; Gastritis, Atrophic; Gastroesophageal Reflux; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Retrospective Studies; Risk Factors; Salicylates; Tetracycline

Antibiotic resistance has increasingly been recognized as the major cause of treatment failure for Helicobacter pylori infection. New therapies for patients with metronidazole- or clarithromycin-resistant H. pylori are needed.. To investigate the role of nitrofurantoin quadruple therapy for the treatment of H. pylori.. Patients with confirmed H. pylori infection received nitrofurantoin (100 mg t.d.s.), omeprazole (20 mg b.d.), Pepto-Bismol (two tablets t.d.s.), and tetracycline (500 mg t.d.s.) for 14 days. Four or more weeks after the end of therapy, outcome was assessed by repeat endoscopy with histology and culture or urea breath testing.. Thirty patients were entered, including 25 men and five women; the mean age was 54.9 years. The most common diagnoses were duodenal ulcer (23%) and GERD (18%). The intention-to-treat cure rate was 70% (95% CI: 50.6-85%). Nitrofurantoin quadruple therapy was more effective with metronidazole-sensitive strains (88%; 15 out of 17) than with metronidazole-resistant strains (33%; three out of nine; P=0.008). Two of the treatment failures had pre-treatment isolates susceptible to metronidazole, which were resistant after therapy.. Because nitrofurantoin quadruple therapy performed inadequately in the presence of metronidazole resistance, we conclude that nitrofurantoin is unlikely to find clinical utility for the eradication of H. pylori.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Anti-Ulcer Agents; Bismuth; Breath Tests; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Nitrofurantoin; Omeprazole; Organometallic Compounds; Salicylates; Tetracycline; Treatment Outcome; Urea

The inflammatory process involving Helicobacter pylori-associated gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal and in vitro studies suggesting that tetracyclines have both anti-inflammatory and tissue-protectant effects unrelated to their antimicrobial activity. We attempted to modulate components of H. pylori's inflammatory process by: (i) eliminating the infection; (ii) using tetracycline to alter the host's reaction to the infection without reducing the bacterial load; and (iii) using calcium to counteract the effect of excessive dietary salt.. We conducted a 16-week placebo-controlled clinical trial with 374 H. pylori-associated gastritis patients randomly assigned to one of five groups: (1) triple therapy consisting of metronidazole, amoxicillin and bismuth subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) calcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracycline; or (5) placebo.. Subjects in the tetracycline and triple therapy groups, but not the calcium carbonate only group, showed a reduction in inflammation and epithelial damage vs. those in the placebo group, independent of a change in H. pylori density and other factors. Our results also indicate that epithelial damage may be affected by mechanisms independent of H. pylori density or inflammation.. The results are consistent with the hypothesis that tetracycline can decrease inflammation independent of a reduction in the bacterial load. More research is needed to investigate mechanisms leading to epithelial damage which are independent of H. pylori density and inflammation.

Topics: Adult; Aged; Amoxicillin; Antacids; Anti-Bacterial Agents; Bismuth; Calcium Carbonate; Drug Therapy, Combination; Epithelium; Female; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Male; Metronidazole; Middle Aged; Organometallic Compounds; Penicillins; Placebos; Risk Factors; Salicylates; Stomach Neoplasms; Tetracycline; Treatment Outcome

At present, the prevalence of Helicobacter pylori (H. pylori) in complicated peptic ulcer and the effect of H. pylori eradication on complicated peptic ulcer have not been fully established. In this study, we report the prevalence of H. pylori in peptic ulcer patients complicated with gastric outlet obstruction, effectiveness of oral eradication therapy on these patients, and their long-term follow up.. Ten consecutive patients presenting with clinically and endoscopically significant obstructed peptic ulcers were included in this study. During each endoscopy, seven gastric biopsy specimens were obtained and analyzed for H. pylori colonization.. The antral mucosal biopsy specimens were positive for H. pylori in nine patients. H. pylori infection was eradicated and complete ulcer healing was observed in all patients. The mean follow-up period was 14 (7-24) months. One patient had duodenal perforation and underwent surgical intervention following medical treatment, despite the eradication of H. pylori. Ulcer recurrence was noted in two (22.2%) of nine patients, and in one of them the recurrent ulcer was complicated with obstruction (11. 1%). The mean time to ulcer recurrence was 17 months (range, 10-24 months). The biopsies and CLOtests were H. pylori negative at the time of ulcer or erosion recurrence in two patients.. We suggest that H. pylori eradication may improve the resolution in obstructive ulcer cases with colonization.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Female; Follow-Up Studies; Gastric Outlet Obstruction; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline; Treatment Outcome

In order to investigate the potential of Helicobacter pylori (HP) to induce dyspepsia, we performed a randomized prospective study on the long-term effect of HP-eradication on symptoms of HP-positive dyspeptic patients in whom other organic causes for dyspepsia were carefully ruled out.. 201 patients referred to our endoscopy unit with dyspeptic symptoms for at least six months entered the study. Patients with previous peptic ulcer were excluded.. After endoscopy of the upper alimentary tract and 13C-urea breath test, patients with active peptic ulcer, hiatal hernia, macroscopic evidence for esophagitis and negative HP-status were excluded. The remaining patients underwent abdominal sonography, H2-exhalation test with lactose, and 24-h pH monitoring in order to exclude other organic causes for dyspepsia. In 20 patients, dyspepsia was assumed to be due to HP-gastritis. Patients received eradication therapy and were controlled as assessed by the 13C-urea breath test six weeks and six months after completion of the therapy. Dyspeptic symptoms were monitored by means of a validated symptom score.. Out of 20 patients with HP-gastritis the first eradication treatment was successful in 13, while seven patients remained HP-positive after antibiotic treatment. Six months after completion of therapy the symptoms of HP-eradicated patients improved considerably (score values 17.4 +/- 1.5 and 10.2 +/- 0.8, respectively, p < 0.01) whereas symptoms of patients with persistent infection remained unchanged (21.1 +/- 1.7 and 20.4 +/- 1.5, n.s.) and only improved after successful retherapy (20.4 +/- 1.5 and 11.7 +/- 2.1, p < 0.05). In total, 17 of 20 patients (85%) improved after successful eradication. Also, neutrophil infiltration in the gastric mucosa correlated to both dyspeptic symptoms before therapy (r = 0.85) and the decrease in symptom score after HP-eradication (r = 0.61). In contrast, the symptoms of eight patients with gastroesophageal reflux disease were not improved after eradication (20.0 +/- 1.1 and 18.2 +/- 1.0, n.s.). HP-infection per se contributes to dyspepsia. 17 of 20 (85%) HP-positive dyspeptic patients improved after HP-eradication, when other potential organic causes for dyspepsia had been ruled out. However, many patients did not completely recover but the symptoms only partly decreased which parallels the persistence of part of the inflammatory infiltration in the gastric mucosa. This emphasizes the importance of HP-gastritis as an organic disease causing dyspeptic symptoms.

Topics: Adult; Aged; Amoxicillin; Anti-Ulcer Agents; Bismuth; Clarithromycin; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyspepsia; Female; Follow-Up Studies; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Salicylates; Tetracycline; Treatment Outcome

Metronidazole remains a key component of H. pylori infection therapy. It has been suggested that despite resistance, metronidazole may be effective when given at high dose with bismuth, tetracycline, and a proton pump inhibitor (quadruple therapy).. To prospectively evaluate metronidazole quadruple therapy for treatment of metronidazole resistant H. pylori infection in the United States.. Patients infected with metronidazole resistant H. pylori were prospectively prescribed 14 days of quadruple therapy consisting of metronidazole 500 mg t.d.s., tetracycline 500 mg q.d.s., two bismuth subsalicylate tablets q.d.s., and omeprazole 20 mg o.d.. A total of 26 patients were entered into the study; 22 for their first treatment and four as re-treatment for failed therapy. Of the 26 patients, 24 were cured (cure rate 92%; 95% CI: 78-99%). Both treatment failures reported full compliance to 14 days of therapy. Side-effects were common and resulted in premature discontinuation of therapy in 31%. Premature discontinuation did not reduce the cure rate.. Quadruple metronidazole combination therapy is effective despite the presence of metronidazole resistance and should be considered as either first line therapy or for failures of twice-a-day combination therapies.

Topics: Aged; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Omeprazole; Organometallic Compounds; Patient Compliance; Prospective Studies; Salicylates; Tetracycline; Treatment Outcome

To determine whether an enhanced compliance program (ECP) improves patient compliance with bismuth subsalicylate, metronidazole, and tetracycline hydrochloride (BMT) triple therapy for the treatment of Helicobacter pylori infection and to identify factors that affect compliance with therapy.. A randomized controlled trial conducted in 4 staff-model health centers of a health maintenance organization in Massachusetts.. A total of 125 patients 18 years of age or older with peptic ulcer disease or dyspepsia whose clinicians prescribed BMT triple therapy for 14 days were randomized to a control group or to the ECP group. The ECP group received medication counseling (written and oral) from a pharmacist, along with a medication calendar and a minipillbox, as well as a follow-up telephone call after initiation of therapy. Compliance was assessed by a pill count, and factors affecting adherence to the regimen were identified by patients' reports.. There was no statistically significant difference between the 2 groups in the number of patients taking more than 60% of the medications (89% of the control group vs 95% of the ECP group; P>.30). However, there was a statistically significant difference in the number of patients taking more than 90% of the medications (67% of the control group vs 89% of the ECP group; P<.01). An intention-to-treat analysis confirmed these results. The most frequently reported adverse effect was gastrointestinal intolerance. Other factors reported to affect compliance included the frequency of dosing and the number of pills.. These findings suggest that although adverse effects were common, most patients were able to complete 60% or more of the 2-week regimen. An ECP further improved the percentage of medications taken.

Topics: Adult; Aged; Anti-Bacterial Agents; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Health Maintenance Organizations; Helicobacter Infections; Helicobacter pylori; Humans; Male; Massachusetts; Metronidazole; Middle Aged; Organometallic Compounds; Patient Compliance; Program Evaluation; Salicylates; Tetracycline; Treatment Outcome

Quadruple therapy (bismuth, metronidazole and tetracycline (BMT) + proton pump inhibitor) is touted as being > 95% effective, regardless of metronidazole resistance. We tested a 10-day b.d. quadruple therapy for treatment of H. pylori infection.. Anti-H. pylori therapy consisted of lansoprazole 15 mg b.d. plus tetracycline 500 mg b.d., metronidazole 500 mg b.d., and swallowable Pepto-Bismol caplets (2 b.d.) for 10 days. H. pylori status was evaluated by culture and histology before and 4 or more weeks after therapy.. The cure rate for intention-to-treat was 70%. Treatment success was calculated overall and separately in relation to antimicrobial resistance patterns. The cure rate among the metronidazole-sensitive isolates was 89.7% (26 of 29) vs. 41.2% (7 of 17) of the metronidazole-resistant isolates (P < 0.005). Moderate (n = 1) or severe (n = 3) side-effects were experienced in four patients with only one withdrawing because of side-effects.. Twice a day quadruple therapy is effective for metronidazole-sensitive strains but its usefulness is markedly reduced by the presence of pre-treatment metronidazole resistance. Twice a day quadruple therapy can be recommended in locations where background metronidazole resistance is uncommon. Possibly, 14-day therapy or a higher dosage of metronidazole provide better results with metronidazole-resistant H. pylori.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Enzyme Inhibitors; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Proton Pump Inhibitors; Salicylates; Smoking; Tetracycline; Tetracyclines

In an attempt to increase the efficacy and simplicity of FDA-approved regimens for Helicobacter pylori, we studied (1) addition of an inexpensive antibiotic (amoxicillin) to twice-daily ranitidine bismuth citrate (RBC)-clarithromycin dual therapy, and (2) substitution of RBC for bismuth subsalicylate + H2-receptor antagonist in bismuth-based triple therapy.. Subjects with previously untreated Helicobacter pylori infection documented by 13C-urea breath test plus either endoscopic biopsy or serology were randomly assigned to a 2-wk course of (1) RBC 400 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d. (RAC), or (2) RBC 400 mg b.i.d., metronidazole 250 mg t.i.d., and tetracycline 500 mg t.i.d. (RMT). Repeat breath test was performed 4 wk after the completion of therapy.. Intent-to-treat and per-protocol cure rates for RAC were 46 of 50 patients (92%) and 45 of 47 patients (96%); for RMT they were 40 of 50 patients (80%) and 37 of 42 patients (88%). Study drugs were stopped due to side effects in three patients (6%) taking RAC and six patients (12%) taking RMT.. Twice-daily RBC-based triple therapy with clarithromycin and amoxicillin produces Helicobacter pylori eradication rates over 90%, which is comparable to rates seen with proton pump inhibitor-based triple therapies. RBC also may be substituted for bismuth subsalicylate and an + H2-receptor antagonist in standard bismuth-based triple therapy.

Topics: Adult; Amoxicillin; Antacids; Anti-Bacterial Agents; Anti-Ulcer Agents; Biopsy; Bismuth; Breath Tests; Carbon Isotopes; Clarithromycin; Drug Combinations; Female; Follow-Up Studies; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Metronidazole; Organometallic Compounds; Penicillins; Peptic Ulcer; Proton Pump Inhibitors; Ranitidine; Salicylates; Tetracycline; Urea

Helicobacter pylori is associated with gastritis, peptic ulcer disease, and gastric cancer. Since gastric cancer is common in Peru, eradication of H. pylori may help to reduce the occurrence of gastric cancer. This study involved three randomized trials to determine the efficacy of four different triple-drug therapy regimens. The most successful regimen was furazolidone combined with bismuth subsalicylate and amoxicillin, which eradicated infection in 82% of patients. Patients successfully treated were followed every 2-3 months to determine the recurrence rate of H. pylori infection. Of 105 patients with H. pylori eradication documented by pathology and culture, 52% (55) returned for follow-up endoscopy, and in 73% (40) of these 55 the infection recurred during the 8-month follow-up period. Thirty-five patients from whom H. pylori was eradicated and who were tested for antibodies to H. pylori remained consistently seropositive. Rapid recurrence of H. pylori infection after successful eradication suggests that measures other than antimicrobial therapy are needed to fight H. pylori in developing countries.

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Female; Follow-Up Studies; Furazolidone; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peru; Recurrence; Salicylates; Tetracycline; Tinidazole

Bismuth subsalicylate, tetracycline hydrochloride, and metronidazole are widely used in combination for the treatment of Helicobacter pylori infections. As a result, there is renewed interest in the interaction between tetracycline and bismuth subsalicylate.. To determine whether the observed decrease in tetracycline bioavailability is due to the active drug bismuth subsalicylate via complexation, or to magnesium aluminum silicate (Veegum), an inactive excipient present only in the liquid formulation of bismuth subsalicylate, which might adsorb the tetracycline, rendering it unavailable for systemic absorption.. Eleven healthy volunteers participated in a randomized three-period, three-treatment complete crossover study with a 7-day washout interval between treatments. After an overnight fast, subjects received a 500-mg capsule of tetracycline hydrochloride with either tap water, 30 mL of bismuth subsalicylate (525 mg) liquid containing Veegum (Pepto-Bismol), or 30 mL of a specially formulated bismuth subsalicylate (525 mg) liquid without Veegum. Blood was collected for 24 hours after each dose of tetracycline. Serum was assayed for tetracycline concentration by HPLC. In addition, standard in vitro ultraviolet spectrophotometric methods were used to determine the capacity for complexation of bismuth with tetracycline and for adsorption of tetracycline to Veegum.. Compared with the reference treatment of tetracycline hydrochloride with water, the liquid formulation of bismuth subsalicylate containing Veegum decreased the maximum serum concentration (Cmax) of tetracycline by 21% and the serum tetracycline AUC by 27% (p < 0.001). The bismuth subsalicylate formulation without Veegum resulted in decreases in Cmax and AUC of 11% and 13%, respectively (p > 0.05 vs. tetracycline hydrochloride with water). Multiple linear regression analysis of the spectral absorbance data demonstrated a calculated recovery of tetracycline of 100.9% and, therefore, a lack of in vitro complexation with bismuth. At pH 1.2, the amount of tetracycline adsorbed to Veegum ranged from 91.5% to 97.2% over the concentration range of 0.25 to 2 mg/mL. At pH 7.0, the values ranged from 82.9% to 83.9% over the concentration range of 0.25 to 1 mg/mL.. In vitro and in vivo data from this study indicate that Veegum, a suspending agent, and not the active agent bismuth subsalicylate, is the primary ingredient in liquid formulations of bismuth subsalicylate responsible for a decrease in tetracycline bioavailability. In addition, the mechanism of interaction is not likely due to complexation between tetracycline and bismuth subsalicylate, as previously postulated, but rather is caused by adsorption of tetracycline to the excipient Veegum, which is present only in the liquid formulation of bismuth subsalicylate. The clinical relevance of this interaction has not been determined.

Topics: Adolescent; Adult; Aluminum Compounds; Antacids; Biological Availability; Bismuth; Chromatography, High Pressure Liquid; Cross-Over Studies; Female; Humans; Intestinal Absorption; Magnesium Compounds; Male; Middle Aged; Organometallic Compounds; Regression Analysis; Salicylates; Silicates; Tetracycline

The present study was designed to compare the efficacy and tolerability of triple therapy and dual therapy for Helicobacter pylori in duodenal ulcer patients and to evaluate the long-term clinical course of ulcer disease. Forty duodenal ulcer patients with proven H. pylori infection were enrolled into the study and randomly treated with either triple therapy consisting of bismuth subsalicylate, metronidazole and tetracycline plus ranitidine or with dual therapy comprising omeprazole and amoxicillin. Patients were investigated clinically and endoscopically including assessment of H. pylori infection by means or rapid urease test, culture, histology and urea breath testing 4 weeks after cessation of eradication therapy, in 1-year intervals and when dyspeptic symptoms recurred. One patient of each group was lost during follow-up. H. pylori infection was cured by triple therapy in 84.2% and by dual therapy in 78.9% (p = 1.00). During follow-up, all patients with cure of H. pylori infection (n = 31) remained in stable remission with respect to duodenal ulcer disease, while 6 out of 7 patients persistently infected with H. pylori developed an ulcer relapse (p < 0.001). One patient with cured infection had had an episode of dyspeptic symptoms requiring pharmacotherapy and in another 3 patients mild refluxesophagitis without necessity of medical treatment had been detected on the occasion of a scheduled endoscopy. In the short-term, cure of the infection resulted in a marked reduction of the degree of antral gastritis and in a loss of activity in all but one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Duodenal Ulcer; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Penicillins; Prospective Studies; Ranitidine; Recurrence; Salicylates; Tetracycline; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Azithromycin; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Peptic Ulcer; Ranitidine; Salicylates; Tetracycline

We evaluated whether therapy designed to eradicate Helicobacter pylori infection resulted in a reduction in rebleeding in patients with peptic ulcer disease. Patients presenting because of major upper gastrointestinal hemorrhage from peptic ulcer and whose ulcers healed in a study in which they were randomized to receive ranitidine alone or triple therapy plus ranitidine were followed up regularly with endoscopy. No maintenance anti-ulcer therapy was given after ulcer healing.. Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet), and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. Development of ulcer recurrence with or without recurrent upper gastrointestinal bleeding was evaluated.. Thirty-one patients with major upper gastrointestinal bleeding from peptic ulcer were studied; 17 received triple therapy and 14 ranitidine alone. Major rebleeding occurred significantly (p = 0.031) more often in those in the ranitidine group (28.6%), compared with none (0%) in the triple therapy group.. Eradication of H. pylori infection reduces the rate of ulcer recurrence and rebleeding in complicated ulcer disease.

Topics: Adult; Aged; Bismuth; Drug Therapy, Combination; Follow-Up Studies; Gastrointestinal Hemorrhage; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Peptic Ulcer; Prospective Studies; Ranitidine; Recurrence; Salicylates; Tetracycline

Treatment with amoxicillin and omeprazole resulted in encouraging Helicobacter pylori eradication rates in pilot studies that included medium term follow up. These results were evaluated in a prospective, randomised and controlled study. Forty patients with active duodenal ulcer disease and H pylori colonisation of the gastric mucosa were randomly assigned to receive either omeprazole (20 mg twice daily) and amoxicillin suspension (500 mg four times daily) for two weeks (group I) or bismuth subsalicylate (600 mg three times daily), metronidazole (400 mg three times daily), tetracycline (500 mg three times daily), and ranitidine (300 mg in the evening) for two weeks (group II). Study medication was followed in both groups by a four week treatment course with 300 mg ranitidine up to the final examination. One patient from each group was lost to follow up. H pylori was eradicated in 78.9% of group I and 84.2% of group II (p = 1.00). All ulcers in patients on omeprazole plus amoxicillin healed but in the triple treatment group four patients had residual peptic lesions after six weeks (ulcer healing rate: 78.9%, p = 0.11). Complete pain relief occurred after a median duration of 1 day in group I and of 6 days in group II (p = 0.03). There were no major complications in either group but minor side effects were more frequently recorded in patients on triple therapy (63.2% v 15.8%, p < 0.01). In conclusion, two weeks of treatment with omeprazole plus amoxicillin is as good as triple therapy plus ranitidine in eradicating H pylori but seems better with regard to safety, pain relief, and ulcer healing. Thus, amoxicillin plus omeprazole should be recommended as the treatment of choice in eradicating H pylori in patients with duodenal ulcer disease.

Topics: Adult; Aged; Amoxicillin; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Prospective Studies; Salicylates; Tetracycline

Triple therapies using bismuth, metronidazole and tetracycline or amoxicillin were the first truly successful anti-H. pylori therapies. Metronidazole resistance has become an increasing problem that has severely limited the usefulness of the original triple therapy. Resistance to tetracycline or amoxicillin has not been reported and both are effective against H. pylori. We therefore tested a new triple therapy consisting of 500 mg tetracycline, 500 mg amoxicillin, and 2 tablets of bismuth subsalicylate each administered four times daily (with meals and at bedtime) for 14 days during treatment with ranitidine 300 mg daily. H. pylori eradication was defined as no evidence of H. pylori one or more months after stopping therapy. H. pylori status was evaluated by a combination of urea breath test and histology. Sixteen patients with H. pylori infection and active peptic ulcers were enrolled. The new triple therapy was successful in only 7 individuals (43%). Metronidazole appears to be critical for the effectiveness of the original triple therapy. An alternative to metronidazole will be required for a new successful triple therapy.

Topics: Adult; Aged; Amoxicillin; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Stomach Ulcer; Tetracycline

To determine the effect of treating Helicobacter pylori infection on the recurrence of gastric and duodenal ulcer disease.. Follow-up of up to 2 years in patients with healed ulcers who had participated in randomized, controlled trials.. A Veterans Affairs hospital.. A total of 109 patients infected with H. pylori who had a recently healed duodenal (83 patients) or gastric ulcer (26 patients) as confirmed by endoscopy.. Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet) and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given.. Endoscopy to assess ulcer recurrence was done at 3-month intervals or when a patient developed symptoms, for a maximum of 2 years.. The probability of recurrence for patients who received triple therapy plus ranitidine was significantly lower than that for patients who received ranitidine alone: for patients with duodenal ulcer, 12% (95% CI, 1% to 24%) compared with 95% (CI, 84% to 100%); for patients with gastric ulcer, 13% (CI, 4% to 31%) compared with 74% (44% to 100%). Fifty percent of patients who received ranitidine alone for healing of duodenal or gastric ulcer had a relapse within 12 weeks of healing. Ulcer recurrence in the triple therapy group was related to the failure to eradicate H. pylori and to the use of nonsteroidal anti-inflammatory drugs.. Eradication of H. pylori infection markedly changes the natural history of peptic ulcer in patients with duodenal or gastric ulcer. Most peptic ulcers associated with H. pylori infection are curable.

Topics: Adult; Aged; Aged, 80 and over; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Ranitidine; Recurrence; Risk Factors; Salicylates; Stomach Ulcer; Tetracycline

To determine whether antimicrobial therapy for Helicobacter pylori infection accelerates the healing of duodenal ulcers.. Single-blind, randomized, controlled trial.. Veterans Affairs hospital.. One hundred and five patients with endoscopically verified duodenal ulcers.. Patients received either ranitidine, 300 mg/d, or ranitidine, 300 mg/d, plus "triple therapy" (2 g/d of tetracycline, 750 mg/d of metronidazole, and 5 or 8 bismuth subsalicylate tablets per day). Triple therapy was administered for only the first 2 weeks of ulcer treatment.. Videoendoscopic assessment of ulcer status was done until ulcer healing was complete. Evaluations were done after 2, 4, 8, 12, and 16 weeks of therapy.. Ulcer healing was more rapid in patients receiving ranitidine plus triple therapy than in patients receiving ranitidine alone (P less than 0.01). The cumulative percentages of patients with healed ulcers in the group receiving ranitidine plus triple therapy and in the group receiving ranitidine alone were as follows: 37% and 18% after week 2; 74% and 53% after week 4; 84% and 68% after week 8; 96% and 80% after week 12; and 98% and 84% after week 16.. Combined therapy with anti-H. pylori agents and ranitidine was superior to ranitidine alone for duodenal ulcer healing. Our results indicate that H. pylori plays a role in duodenal ulcer disease.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Ranitidine; Salicylates; Single-Blind Method; Tetracycline

Aim. There is a paucity of data on the efficacy of empiric H. pylori treatment after multiple treatment failures. The aim of this study is to examine the efficacy of empiric salvage therapy as a second through sixth line treatment. Methods. In this single gastroenterology center prospective study in Montreal, Canada, patients with failed H. pylori treatment were offered empiric salvage therapy based on the patients' previous antibiotic exposure. Enrollment occurred after 1-5 previous failed attempts and eradication determined at least 4 weeks after completion of treatment. Results. 205 treatments were attempted in 175 patients using 7 different regimens. Eradication was achieved in 154 attempts (PP = 81% (154/191), ITT = 75% (154/205)). Bismuth quadruple therapy (BQT) had higher eradication success (PP = 91% (102/112), ITT = 84% (102/121)) when compared to all PPI triple therapies combined (PP = 66% (49/74), absolute risk reduction (ARR): 25% (95% CI: 13-37), ITT = 62% (49/79), ARR: 22% (95% CI: 10-35), and p < 0.001) and when compared to levofloxacin triple therapy (PP = 66% (40/61), ARR: 26% (95% CI: 13-39), ITT = 61% (40/66), and ARR: 24% (95% CI: 10-37)). Eradication was achieved in a high proportion with BQT on attempt two (PP = 94% (67/71), ITT = 91% (67/74)), three (PP = 85% (17/20), ITT = 71% (17/24)), four (PP = 100% (11/11), ITT = 92% (11/12)), and five (PP = 86% (6/7), ITT = 75% (6/8)). Patients with previous combined bismuth and tetracycline exposure had a lower proportion of eradication compared to patients without such an exposure (PP: 60% (6/10) versus 95% (94/99), ARR: 35% (95% CI: 11-64), and p < 0.001; ITT: 55% (6/11) versus 90% (94/105), ARR: 35% (95% CI: 10-62), and p < 0.01). Conclusions. Salvage therapy with a bismuth quadruple regimen is superior to triple therapies and is effective for second through fifth line empirical treatment (≥85% PP, ≥70% ITT). Successful eradication is significantly lower with BQT if a similar bismuth based regimen was used in the past.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bismuth; Canada; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Intention to Treat Analysis; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Organometallic Compounds; Prospective Studies; Proton Pump Inhibitors; Salicylates; Salvage Therapy; Tetracycline; Treatment Failure; Treatment Outcome; Young Adult

We evaluated the effect of optimized doses and dosing schedules of metronidazole, tetracycline, and bismuth-metronidazole-tetracycline (BMT) triple therapy with only 1 day of dosing on Helicobacter pylori SS1 titers in a mouse model. A reduction of bacterial titers was observable with 22.5 and 112.5 mg of metronidazole per kg of body weight (as well as BMT) given twice daily and four times daily (QID). Two hundred milligrams of tetracycline per kilogram, given QID, resulted in only a slight reduction of H. pylori titers in the stomach. We argue that optimization of doses based on antimicrobial drug levels in the animal and shortened (1 or 2 days) drug administration can be used to facilitate early evaluation of putative anti-H. pylori drug candidates in lieu of using human doses and extended schedules (7 to 14 days), as can be deduced from the results seen with these antimicrobial agents.

Topics: Animals; Bismuth; Disease Models, Animal; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Mice; Mice, Inbred C57BL; Organometallic Compounds; Salicylates; Tetracycline

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Autoimmune Diseases; Bismuth; Drug Therapy, Combination; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; L-Lactate Dehydrogenase; Metronidazole; Omeprazole; Organometallic Compounds; Purpura, Thrombocytopenic, Idiopathic; Salicylates; Tetracycline

Topics: Bismuth; Drug Interactions; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline

Topics: Bacterial Infections; Bismuth; Child; Gastric Mucosa; Gastritis; Helicobacter heilmannii; Humans; Male; Metronidazole; Organometallic Compounds; Salicylates; Tetracycline

To determine the pharmacoeconomic impact of antimicrobial treatment of peptic ulcer disease (PUD) in a large urban jail.. Retrospective comparison of PUD-related pharmacy and laboratory expenditures over a 2-year period before and after the institution of a PUD treatment protocol with the priority of Helicobacter pylori eradication for inmates in Rikers Island Correctional Facility.. After the protocol was adopted, total pharmacy-related and laboratory-related expenses for PUD care decreased by 40.2%, and expenditures for ranitidine declined by 52.2%. There was an increase in spending for antimicrobial agents and H. pylori antibody testing, but this was insignificant compared to the savings generated by decreased ranitidine usage. Annual savings in our facility as a result of this intervention were $123,449.. Modern therapeutic strategies for PUD aimed at eradicating H. pylori can result in significant savings in the institutional setting; these savings are largely attributable to the decreased usage of histamine-2 receptor antagonists.

Topics: Adult; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Male; Metronidazole; New York City; Organometallic Compounds; Peptic Ulcer; Prisons; Ranitidine; Retrospective Studies; Salicylates; Tetracycline; Urban Health

Helicobacter pylori has been proposed as a major determinant in multiple gastric disorders. We describe the case of a young adult with a long-standing medical history of sideropenic anaemia and of oral iron consumption dependence with a chronic superficial H. pylori-positive gastritis. All other causes of sideropenic anaemia were carefully excluded. Histology showed a peculiar pattern of non-active H. pylori-positive gastritis. The bacterium was a non-VacA-producing strain. The first attempt at eradication caused a reduction in bacterial load and led to a partial normalization of haematologic variables without improving the ferritin level. A successful second course of eradication therapy completely reversed the anaemia and restored the iron deposit, which persisted at the 29-month follow-up. H. pylori infection can be involved in unexplained cases of iron deficiency anaemia in adults, and its cure can normalize the haematologic picture.

Topics: Adult; Anemia, Iron-Deficiency; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Omeprazole; Organometallic Compounds; Salicylates; Tetracycline

This study had three goals: (1) Identify patients with Helicobacter pylori, treat their disease, monitor their progress, and determine that they are no longer infected. (2) Realize a cost savings for our health clinic. (3) Improve patient quality of life. These three goals have been met.

Topics: Amoxicillin; Bismuth; Cost Savings; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metronidazole; Military Personnel; Organometallic Compounds; Peptic Ulcer; Salicylates; Tetracycline; United States; Utah

The sanctuary site where Helicobacter pylori evades antimicrobial therapy is unknown, but considerable data exist about an intracellular location for H pylori. Ten H pylori-infected volunteers received standard triple antimicrobial therapy for 2 weeks. Gastric mucosal biopsy specimens were obtained with jumbo forceps on therapy days 0, 3, 14, and 42. Hematoxylin-eosin staining was used for classification of gastritis and the Genta stain for the visualization of H pylori. Immunohistochemical staining was used to detect HLA-DR antigens, human heat shock protein (HSP60), and the bacterial HSP60 antigen. Bacterial HSP60 was expressed on the mucosal surface and within epithelial cells. No such expression of human HSP60 was found, which supports a bacterial origin for the intracellular HSP60. Coexpression of bacterial HSP60 and HLA-DR was always observed, indicating an ongoing local immune response. Infection was cleared on day 14, but when examined 4 weeks after completion of therapy, Genta staining indicated that only five volunteers remained free of H pylori. However, results of immunohistochemical staining were negative at this time for only two volunteers. Disappearance of intracellular expression of bacterial HSP60 remained after therapy and correlated with the intensity of chronic inflammatory cell infiltration. These data are consistent with the intracellular localization of H pylori having a role in inflammation and as a protective strategy against extracellular antibacterial activity.

Topics: Adult; Antacids; Anti-Bacterial Agents; Antibodies, Bacterial; Antibodies, Monoclonal; Antitrichomonal Agents; Bismuth; Chaperonin 60; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epithelium; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; HLA-DR Antigens; Humans; Immunohistochemistry; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Tetracycline; Time Factors

Three cheetahs (Acinonyx jubatus) had a clinical history of chronic spiral bacteria-associated gastritis and three cheetahs had no clinical history of gastritis. Gastric biopsies were obtained from all six cheetahs prior to treatment for gastritis and 3 wk and 1 yr posttreatment. The cheetahs were treated with tetracycline hydrochloride 500 mg p.o. q.i.d., metronidazole 250 mg p.o. q.i.d., and bismuth subsalicylate 300 mg p.o. q.i.d. Each drug was administered concurrently for 7 days. Following this treatment, each cheetah was maintained on 300 mg bismuth subsalicylate p.o. s.i.d. for 1 yr. The three cheetahs with a history of gastritis were culture positive for Helicobacter acinonyx and remained positive during the entire study. The three cheetahs with no clinical history of gastritis were culture negative for H. acinonyx, but gastric biopsies revealed Gastrospirillum-like bacteria (tentatively named Helicobacter heilmannii) pretreatment. Gastric biopsies were negative for H. heilmannii on subsequent examinations. Although the treatment did not eradicate H. acinonyx, it did provide symptomatic relief from the vomiting, anorexia, and weight loss associated with clinical gastritis. The use of endoscopically guided gastric mucosal biopsies for urease testing and histopathologic examination of Warthin-Starry-stained sections is a sensitive and specific method of diagnosing spiral bacteria-associated gastritis. Treatment of spiral bacteria-associated gastritis in cheetahs should include the rational use of antibiotics (tetracycline or amoxicillin and metronidazole), bismuth compounds, and omeprazole and evaluation of husbandry methods to reduce stress.

Topics: Acinonyx; Animals; Anti-Bacterial Agents; Antitrichomonal Agents; Biopsy; Bismuth; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Gastric Mucosa; Gastritis; Gram-Negative Bacterial Infections; Helicobacter; Helicobacter Infections; Lymphocytes; Male; Metronidazole; Organometallic Compounds; Prospective Studies; Salicylates; Sensitivity and Specificity; Tetracycline; Time Factors

Topics: Amoxicillin; Anti-Bacterial Agents; Antitrichomonal Agents; Bismuth; Cost of Illness; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds; Penicillins; Peptic Ulcer; Pilot Projects; Salicylates; Tetracycline

Topics: Amoxicillin; Anti-Bacterial Agents; Anti-Ulcer Agents; Bismuth; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Organometallic Compounds; Penicillins; Peptic Ulcer; Ranitidine; Salicylates; Tetracycline

Topics: Anti-Bacterial Agents; Bismuth; Drug Therapy, Combination; Eczema; Gastroenteritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Recurrence; Salicylates; Tetracycline

Fifty patients with relapsing or complicated Helicobacter pylori positive duodenal (n = 41) or gastric ulcer disease (n = 9) and failure of a combined treatment with omeprazole plus amoxycillin to eradicate H. pylori infection were re-treated with either oral triple therapy (bismuth subsalicylate, metronidazole, tetracycline) plus ranitidine [group I: n = 22] or high-dose omeprazole (40 mg b.d. to t.d.s.) plus amoxycillin (1 g t.d.s.) [group II: n = 28].. Patients of group I and II had similar demographic and clinical characteristics. The overall proportion of eradication of H. pylori infection was 81.8% in group I and 78.6% in group II (P = N.S.) as judged from negative bacterial findings by means of an urease test, specific culture and histology after modified Giemsa stain. Ulcer healing was observed in all patients after a maximum duration of 10 weeks. Ten patients on triple therapy and only one patient on omeprazole plus amoxycillin (45.5% vs. 3.6%; P < 0.001) complained of side effects without necessity of discontinuation of the study medication in either group. Twenty patients (group I: n = 10; group II: n = 10) with relapsing duodenal ulcer disease and successful cure were prospectively followed for one year without any evidence of ulcer relapse or H. pylori re-infection.. Oral triple therapy plus ranitidine or high-dose omeprazole plus amoxycillin remain highly effective in eradicating H. pylori infection in patients with peptic ulcer disease and treatment failure of omeprazole/amoxycillin, but the omeprazole enhanced antibiotic monotherapy seems to be superior with regard to side effects. Thus, high-dose omeprazole/amoxycillin is recommended as the treatment of first choice in these selected patients. Triple therapy should be reserved for patients intolerant of amoxycillin.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Amoxicillin; Bismuth; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Omeprazole; Organometallic Compounds; Peptic Ulcer; Prospective Studies; Ranitidine; Recurrence; Salicylates; Tetracycline; Treatment Failure; Treatment Outcome

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.. 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.. 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.. We conclude that the combination of clarithromycin, tetracycline, and bismuth is an effective new therapy for treatment of H. pylori infection.

Topics: Adult; Aged; Bismuth; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Organometallic Compounds; Peptic Ulcer; Ranitidine; Salicylates; Tetracycline; Time Factors

Topics: Amoxicillin; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Omeprazole; Organometallic Compounds; Ranitidine; Salicylates; Tetracycline

Helicobacter pylori infection is associated with exaggerated gastrin release. We investigated whether this abnormality was due to the bacteria or the immune response. Fasting and meal-stimulated 'total' and amidated gastrin were measured in 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after completion of therapy. The exaggerated meal-stimulated gastrin concentration remained unchanged after 2 days of therapy, although the polymorphonuclear cell infiltrate and H. pylori bacteria were no longer evident. The expected fall in gastrin concentration after 14 days of therapy was associated with a reduction in the density of mucosal mononuclear cells, suggesting exaggerated gastrin release was related to chronic inflammation or to H. pylori or its products. The effect of H. pylori on normal progastrin processing was also assessed; 2 control groups were included: 10 H. pylori-uninfected volunteers and 13 patients with H. pylori peptic ulcers. There was a significant difference in the proportion of circulating gastrins that were biologically active amidated gastrins between ulcer patients and uninfected controls (56.7 +/- 4% versus 33.8 +/- 4%, p < 0.001). The proportion of amidated to total gastrins did not increase after successful eradication.

Topics: Adult; Bismuth; Female; Food; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds; Peptic Ulcer; Protein Precursors; Protein Processing, Post-Translational; Salicylates; Tetracycline

25 patients with Helicobacter pylori-associated active duodenal ulcer disease (bleeding: n = 5, penetrating: n = 1, stenosis of the bulb: n = 4, frequent ulcer relapse: n = 18) were treated with 3 x 600 mg bismuth subsalicylate (BSS), 3 x 400 mg metronidazole and 3 x 500 mg tetracycline in addition to 300 mg ranitidine. 23 out of 25 patients (92%) proved to be Helicobacter pylori-negative four weeks after cessation of study medication as judged from negative urease test, specific culture and histology after modified Giemsa staining. 24/25 ulcers (96%) had healed after six weeks. In one patient on NSAIDs a small duodenal ulcer was detected on the final endoscopic examination despite successful Helicobacter pylori eradication. Twelve out of 25 (48%) patients complained side effects that did not lead to discontinuation of therapy. In conclusion, oral triple therapy with BSS, metronidazole and tetracycline is highly effective in Helicobacter pylori eradication, but there was a rather high rate of more or less serious side effects, diminishing the attractiveness of this therapeutic regimen.

Topics: Administration, Oral; Adult; Aged; Bismuth; Drug Administration Schedule; Drug Therapy, Combination; Duodenal Ulcer; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Prospective Studies; Ranitidine; Salicylates; Tetracycline

To establish the rate of Helicobacter pylori recurrence after a standard triple-therapy regimen (bismuth subsalicylate, tetracycline, metronidazole) and determine which clinical factors affect reinfection, we prospectively followed 118 patients after successful H. pylori eradication. Elimination of H. pylori was confirmed by repeat endoscopy and urea breath test 4 wk after completion of therapy. Serial [13C]urea breath tests were performed at 3-month intervals; antral biopsies were used to verify reinfection. Recurrence of H. pylori infection occurred in 4/118 (3.4%) patients. Three of the four relapses occurred in the 1st yr after treatment. Gender, age, ethnic group, alcohol consumption, cigarette use, and gastrointestinal diagnosis do not predict H. pylori recurrence. We conclude that the rate of recurrence after successful H. pylori eradication is low, and that when reinfection takes place, it occurs most commonly within the 1st yr after treatment.

Topics: Bismuth; Drug Therapy, Combination; Female; Follow-Up Studies; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Recurrence; Salicylates; Tetracycline

Topics: Bismuth; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Organometallic Compounds; Peptic Ulcer; Ranitidine; Recurrence; Salicylates; Tetracycline

Helicobacter pylori infection has been associated with gastritis, duodenal ulcer, gastric ulcer, and the epidemic form of gastric carcinoma. Eradication of H. pylori infection has proven to be difficult. Recently, combinations of antimicrobial drugs have been shown to eradicate greater than 50% of infections; however, the results have proven variable, and the factors influencing effectiveness of therapy are unclear. In the present study, the effectiveness of a triple therapy for eradication of H. pylori infection was evaluated. Triple therapy consisted of 2 g tetracycline, 750 mg metronidazole, and five or eight tablets of bismuth subsalicylate daily in 93 patients (70 with duodenal ulcer, 17 with gastric ulcer, and 6 with simple H. pylori gastritis). Combinations of a sensitive urea breath test, serology, culture, and histology were used to confirm the presence of infection, eradication, or relapse. Eradication was defined as inability to show H. pylori greater than or equal to 1 month after ending therapy. The overall eradication rate was 87%. The factors evaluated for their effect on predicting eradication included age, gender, type of disease, duration of therapy, amount of bismuth subsalicylate [five or eight Pepto-Bismol tablets daily (Procter & Gamble, Cincinnati, OH)], and compliance with the prescribed medications. Stepwise regression showed that compliance was the most important factor predicting success; the success rate was 96% for patients who took greater than 60% of the prescribed medications and 69% for patients who took less. For those taking greater than 60% of the prescribed therapy, the eradication rates were similar (a) for patients receiving therapy for 14 days or when tetracycline and bismuth subsalicylate were taken for an additional 14 days; (b) for patients with duodenal ulcer, gastric ulcer, and simple H. pylori gastritis; and (c) whether five or eight bismuth subsalicylate tablets were taken. It is concluded that triple therapy is effective for eradication of H. pylori and that future studies need to take compliance into account for comparisons between regimens.

Topics: Adult; Aged; Aged, 80 and over; Bismuth; Drug Therapy, Combination; Duodenal Ulcer; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Patient Compliance; Regression Analysis; Salicylates; Stomach Ulcer; Tetracycline

An exaggerated increase in meal-stimulated gastrin is a common finding in patients with duodenal ulcer. Duodenal ulcer patients also exhibit an increase in the number of parietal cells, which results in an increase in maximum acid output. There are also data to suggest that acid hypersecretion may not predate the ulcer disease, but is acquired, possibly due to the trophic effects of the exaggerated gastrin release on parietal cells. We investigated meal-stimulated gastrin release in nine Helicobacter pylori-infected individuals; eight patients with chronic duodenal ulcer and one H. pylori-infected healthy control, both before and after therapy designed to eradicate H. pylori infection. We also simultaneously measured intragastric pH in six duodenal ulcer patients. Eradication of the H. pylori infection reversed the exaggerated meal-stimulated gastrin release (gastrin secretion fell from 141 + 16 pg/ml/h before treatment to 98 +/- 7 pg/ml/h after, p less than 0.01) without affecting intragastric pH. Whereas exaggerated meal-stimulated gastrin release may be an important pathogenetic feature of duodenal ulcer disease, we conclude that it is secondary to the H. pylori infection. This study provides further insight into the role of H. pylori in the pathogenesis of duodenal ulcer disease. We postulate that reversal of the abnormalities in gastrin secretion will be associated with a gradual return of gastric secretion to normal.

Topics: Bismuth; Campylobacter Infections; Drug Therapy, Combination; Duodenal Ulcer; Female; Food; Gastrins; Humans; Male; Metronidazole; Middle Aged; Organometallic Compounds; Salicylates; Tetracycline