An Alternative Non-Macrolide, Non-Imidazole Treatment Regimen for Curing Helicobacter pylori and Duodenal Ulcers: Ranitidine Bismuth Citrate Plus Amoxicillin

Background. Because patients who fail to be cured of H. pylori infection following macrolide or imidazole therapy are difficult to treat, there is a clear need for a reasonably effective and simple second-line treatment regimen. The purpose of these two studies was to evaluate the efficacy of ranitidine bismuth citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for healing duodenal ulcers and preventing ulcer relapse.
Materials and Methods. Two identically designed randomized, double-blind, double-dummy studies were conducted in patients with an H. pylori -associated duodenal ulcer. Patients were treated with either RBC 400 mg bid for 4 weeks plus amoxicillin 500 mg qid for 2 weeks, RBC 400 mg bid for 4 weeks and placebo qid for 2 weeks, placebo bid for 4 weeks and amoxicillin 500 mg qid for 2 weeks, or placebo bid for 4 weeks and placebo qid for 2 weeks. Patients with healed ulcers after 4 weeks of treatment were eligible for entry into a 24-week observation phase for the assessment of H. pylori status (culture, histology, and CLOtest^TM) and ulcer relapse.
Results. A total of 229 patients with confirmed H. pylori infection at baseline were evaluated. Of these, 132 whose ulcers had healed entered the 24-week posttreatment observation phase. The combination of RBC plus amoxicillin resulted in higher H. pylori cure rates (55%) and higher duodenal ulcer healing (74%) than did either treatment alone. All treatments were well tolerated.
Conclusions. The combination of ranitidine bismuth citrate plus amoxicillin cures H. pylori infection in more than half of the patients treated. This treatment regimen shows promise as the basis for future non-macrolide, non-imidazole triple therapy regimens for curing H. pylori infection. Such regimens may be appropriate second-line treatment for patients who are resistant to or who are unable to tolerate macrolide- or imidazole-containing therapies.     

Effect of Helicobacter pylori eradication on peptic ulcer disease complicated with outlet obstruction

Background. 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.
Patients and Methods. 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.
Results. 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.
Conclusion. We suggest that H. pylori eradication may improve the resolution in obstructive ulcer cases with colonization.     

Comparative Treatment of Helicobacter pylori–Positive Duodenal Ulcer Using Pantoprazole at Low and High Doses Versus Omeprazole in Triple Therapy

Background. Helicobacter pylori eradication has become the standard treatment for peptic ulcer disease. H. pylori –eradicating triple therapy with omeprazole plus two antibiotics has been used until recently; however, the efficacy of pantoprazole and antibiotics for H. pylori eradication has not been researched thoroughly until now. The aim of this randomized clinical trial was to verify the efficacy of triple oral therapy comparing the effects of pantoprazole using two different doses versus omeprazole twice daily in H. pylori eradication, in ulcer healing and relapses, and in gastritis improvement.
Materials and Methods. We enrolled 243 patients with H. pylori– positive duodenal ulcer and randomized them into three treatment groups: 84 patients (group Ome40) were assigned to receive omeprazole, 20 mg twice daily, plus amoxicillin, 1 gm twice daily, and clarithromycin, 500 mg twice daily for 10 days; 79 patients (group Pan40) were treated with pantoprazole, 40 mg daily, plus amoxicillin and clarithromycin at the same doses as those of group Ome40; and 80 patients (group Pan80) were treated with pantoprazole, 40 mg twice daily, plus amoxicillin and clarithromycin at the same doses as those of group Ome40.
Results. Ulcer healing was observed in 81 of 84 patients (96.4%) in group Ome40; in 66 of 79 patients (83.5%) in group Pan40; and in 77 of 80 patients (96.2%) in group Pan80. H. pylori was eradicated in 79 of 84 patients (94%) in group Ome40; in 63 of 79 patients (79.7%) in group Pan40; and in 75 of 80 patients (93.7%) in group Pan80.
Conclusions. We found that 10-day triple therapy with amoxicillin, clarithromycin, and either pantoprazole, 80 mg daily, or omeprazole, 40 mg daily, is highly effective in ulcer healing and is very well tolerated, achieving the 90% cure recommended for an ideal first-line anti– H. pylori positive duodenal ulcer treatment regimen.     

Curing Helicobacter pylori infection in patients with duodenal ulcer does not provoke gastroesophageal reflux disease

Background. It has been suggested that the incidence of gastroesophageal reflux disease (GERD) increases after successful eradication of Helicobacter pylori infection. We present data on development of GERD from a controlled study of H. pylori eradication in 165 duodenal ulcer patients.
Methods. Patients (mean age, 55 years; 102 men; current smokers; n = 74) were randomly assigned 2 : 1 to receive omeprazole, 40 mg twice daily, in combination with either amoxicillin, 750 mg twice daily, or placebo. Endoscopy and dyspeptic symptoms, including heartburn, were assessed at inclusion and at 6, 12, and 24 months after treatment. In addition, symptoms were assessed at 18 months. Patients with erosive esophagitis or reflux symptoms requiring treatment at inclusion were not included in the study.
Results. Fifty-one of 145 (35%) evaluable patients developed heartburn, and 13 of 145 (9%) developed esophagitis during follow-up. The life-table analysis of the cumulated risk of developing heartburn showed that patients whose H. pylori infection was eradicated had a significantly lower risk for developing heartburn than those with persistent H. pylori infection. The groups did not show any difference in cumulative risk of developing esophagitis.
Conclusion. Our data show that successful eradication of H. pylori infection does not increase the incidence of GERD in duodenal ulcer patients.     

Decreased Prevalence of Helicobacter pylori Infection in Gastroesophageal Reflux Disease

Background.   An increased incidence of reflux esophagitis has been reported after eradication of H. pylori in patients with duodenal ulcer. To determine if H. pylori is associated with lower rates of esophagitis, we studied the prevalence of H. pylori infection in patients with and without reflux esophagitis and a subgroup of patients with concomitant peptic ulcer disease.
Methods.   Patients who underwent esophagogastroduodenoscopy and had diagnostic testing for H. pylori over a 30-month period were studied. H. pylori infection was determined by rapid urease testing, gastric histopathology, or serology. Reflux esophagitis was determined by endoscopic and/or histologic criteria.
Results.   Of 514 patients, 39.5% had H. pylori infection and 22.2% had reflux esophagitis. The prevalence of H. pylori infection in patients with reflux esophagitis was 30.7%, compared with 42.0% in patients without esophagitis ( p = 0.039). The odds ratio for esophagitis risk with H. pylori infection was 0.61 (95% CI, 0.39–0.95). Neither patient age nor gender affected H. pylori prevalence. In patients with duodenal ulcer, H. pylori was present in 36.4% of patients with esophagitis and in 69.2% of patients without esophagitis ( p = 0.018). The odds ratio for esophagitis with H. pylori infection in these patients was 0.25 (95% CI, 0.09–0.73).
Conclusions.   Our study demonstrates that H. pylori infection is significantly less prevalent in patients with reflux esophagitis and may protect against its development. In duodenal ulcer patients, this effect was more dramatic. Further study is required to confirm these findings and elucidate mechanisms underlying possible beneficial effects of H. pylori.     

Indications for treatment of Helicobacter pylori infection: a systematic overview.

OBJECTIVE: To determine (a) the advantages and disadvantages of treatment options for the eradication of Helicobacter pylori and (b) whether eradication of H. pylori is indicated in patients with duodenal ulcer, nonucler dyspepsia and gastric cancer. DATA SOURCES: A MEDLINE search for articles published in English between January 1983 and December 1992 with the use of MeSH terms Helicobacter pylori (called Campylobacter pylori before 1990) and duodenal ulcer, gastric cancer, dyspepsia and clinical trial. Six journals and Current Contents were searched manually for pertinent articles published in that time frame. STUDY SELECTION: For duodenal ulcer the search was limited to studies involving adults, studies of H. pylori eradication and randomized clinical trials comparing anti-H. pylori therapy with conventional ulcer treatment. For nonulcer dyspepsia with H. pylori infection the search was limited to placebo-controlled randomized clinical trials. DATA EXTRACTION: The quality of each study was rated independently on a four-point scale by each author. For the studies of duodenal ulcer the outcome measures assessed were acute ulcer healing and time required for healing, H. pylori eradication and ulcer relapse. For the studies of nonulcer dyspepsia with H. pylori infection the authors assessed H. pylori eradication, the symptoms used as outcome measures and whether validated outcome measures had been used. DATA SYNTHESIS: Eight trials involving duodenal ulcer met our inclusion criteria: five were considered high quality, two were of reasonable quality, and one was weak. Six trials involving nonulcer dyspepsia met the criteria, but all were rated as weak. Among treatment options triple therapy with a bismuth compound, metronidazole and either amoxicillin or tetracycline achieved the highest eradication rates (73% to 94%). Results concerning treatment indications for duodenal ulcer were consistent among all of the studies: when anti-H. pylori therapy was added to conventional ulcer treatment acute ulcers healed more rapidly. Ulcer relapse rates were dramatically reduced after H. pylori eradication. All of the studies involving nonulcer dyspepsia assessed clearance rather than eradication of H. pylori. No study used validated outcome measures. A consistent decrease in symptom severity was no more prevalent in patients in whom the organism had been cleared than in those taking a placebo. Of the studies concerning gastric cancer none investigated the effect of eradication of H. pylori on subsequent risk of gastric cancer. CONCLUSIONS: There is sufficient evidence to support the use of anti-H. pylori therapy in patients with duodenal ulcers who have H. pylori infection, triple therapy achieving the best results. There is no current evidence to support such therapy for nonulcer dyspepsia in patients with H. pylori infection. Much more attention must be paid to the design of nonulcer dyspepsia studies. Also, studies are needed to determine whether H. pylori eradication in patients with gastritis will prevent gastric cancer.     

Helicobacter pylori and peptic ulcer disease.

Medical therapy for duodenal or gastric ulcer disease has traditionally involved gastric acid antisecretory therapy for 4 to 8 weeks to promote initial healing and indefinitely to prevent recurrences of ulcer. The discovery of Helicobacter pylori in most patients with peptic ulcer disease has led to a change in this approach. Therapy designed to eradicate H pylori may facilitate ulcer healing with acid antisecretory agents and, more important, may greatly reduce the incidence of ulcer recurrence, obviating the need for maintenance antisecretory therapy. Regimens designed to eradicate H pylori are difficult to comply with, however, and are associated with adverse effects in some patients. In this article we review the diagnosis and treatment of H pylori infection in patients with peptic ulcer disease and make recommendations regarding the use of conventional ulcer therapies and therapies designed to eradicate H pylori.     

Helicobacter pylori and Peptic Ulcer Disease Therapies: A Survey of Gastroenterologists in Israel

Background. Eradication of Helicobacter pylori has become a therapeutic option in the treatment of patients with peptic ulcer disease. The aim of this study was to evaluate the current management strategies of Israeli gastroenterologists in the diagnosis and treatment of H. pylori- related peptic ulcer disease, 14 years after the discovery of H. pylori.
Materials and Methods. A questionnaire was mailed to all specialists in gastroenterology, members of the Israel Gastroenterological Association (IGA). Replies were received from 60% of Israel Board-certified gastroenterology specialists.
Results. Over 89% of the gastroenterologists (89.1%) noted that they recommend anti- H. pylori treatment. 94.5% said that they treat duodenal ulcer in the first presentation with anti- H. pylori medication and 75% said that they do so in cases of recurrent duodenal ulcer. According to the replies received, there is a strong consensus towards triple treatment as the favored anti -H. pylori treatment; no one noted the use of dual treatment. Seven-day triple treatment was prescribed by 83.6% of the gastroenterologists who responded. Of these, the great majority, 89.1%, stated that they use proton pump inhibitors (PPI) in combination with any two of the following antibiotics: metronidazole (47.3%), tinidazole (29.1%), clarithromycin (61.8%), and amoxicillin (40%).
Conclusion. At the time of the survey, most Israel Board-certified gastroenterology specialists prescribed triple anti- H. pylori treatment of one-week's duration.     

Helicobacter pylori recurrence in patients with duodenal ulcer: Clinical, endoscopic, histologic, and genotypic aspects. A 10-year Brazilian series

BACKGROUND: Recurrence infection following successful eradication of Helicobacter pylori is usually low, except for countries with high prevalence of H. pylori. The aim of this study was to verify H. pylori recurrence rate in patients with duodenal ulcer after eradication and the possible relationship with environmental factors, histologic pattern of the mucosa and bacterial genotype. MATERIALS AND METHODS: One-hundred and ninety-four patients with an active duodenal ulcer and who were successfully treated for H. pylori infection from 1990 to 1999 were studied. A questionnaire was answered about their living conditions, and a 14C-urea breath test was performed. Patients with a positive breath test underwent an upper endoscopy to investigate for possible ulcer recurrence; gastric biopsy samples were than collected for rapid urease test and for histologic assessment. H. pylori vacA and cagA genotype was determined by polymerase chain reaction in those samples with positive urease test. RESULTS: H. pylori infection was detected in 11 patients (recurrence rate of 5.7%) that were not associated with the type of bacterial virulence. In 10 patients the ulcer was healed and all of them were clinically asymptomatic. In eight, histology showed an intensification of gastritis. All 11 patients had adequate housing and sanitary conditions and no other risk for H. pylori recurrence was identified. CONCLUSIONS: The recurrence rate of H. pylori in Brazil was higher than that reported in developed countries, but lower than usually reported in developing ones. Ulcer relapse rarely occurs even in long-term follow up.     

Controlled trial of the effect of cinnamon extract on Helicobacter pylori

Background. Helicobacter pylori has been associated with the pathogenesis of antral gastritis, duodenal ulcer, and gastric lymphoma. Eradication of H. pylori has been shown to reverse or prevent relapse of these diseases. Antimicrobials employed in the eradication of H. pylori are not without adverse effects. Newer treatment modalities, therefore, are required. In vitro studies have shown the effectiveness of cinnamon extract against H. pylori and its urease. In this pilot study, we tested the activity of an alcoholic extract of cinnamon in a group of patients infected with H. pylori.
Materials and Methods. Fifteen patients (11 women, 4 men) aged 16 to 79 years were given 40 mg of an alcoholic cinnamon extract twice daily for 4 weeks; eight patients aged 35 to 79 (7 women, 1 man) received placebo. The amount of H. pylori colonization was measured by the ¹³C urea breath test before and after therapy.
Results. The mean urea breath test counts in the study and control groups before and after therapy were 22.1 and 23.9 versus 24.4 and 25.9, respectively. The cinnamon extract was well tolerated, and side effects were minimal.
Conclusions. We concluded that cinnamon extract, at a concentration of 80 mg /day as a single agent, is ineffective in eradicating H. pylori. Combination of cinnamon with other antimicrobials, or cinnamon extract at a higher concentration, however, may prove useful.     

Pantoprazole suppresses Helicobacter pylori without affecting cure

Background. Short-term, low-dose triple regimens composed of proton-pump inhibitors (PPI) and two antibiotics are the current gold standard therapy for cure of Helicobacter pylori infection. To date, the effect of PPI pretreatment on eradication outcome is not known. The aim of this study was to evaluate the influence of pretreatment with pantoprazole on the efficacy of an ensuing triple therapy.
Methods. In this open, randomized, monocenter, parallel group comparison, 107 patients with duodenal ulcer or functional dyspepsia were assigned to receive one of the following treatment regimens: a 7-day triple therapy with pantoprazole, 40 mg bid; clarithromycin, 250 mg bid; and metronidazole, 400 mg bid, which was either preceded or followed by a 7-day therapy with pantoprazole, 40 mg (P-PCM or PCM-P). Assessment of H. pylori status was performed by a biopsy urease test and ¹³C urea breath test at the initial visit and ¹³C urea breath test at all follow-up visits.
Results. The 7-day pantoprazole pretreatment resulted in a significant decline of the δ values of the ¹³C urea breath test. H. pylori infection was cured in 47 of 52 intention-to-treat patients of the P-PCM group (90%; 95% confidence interval, 79–97%) and in 46 of 53 of the PCM-P group (87%; 95% confidence interval, 75–95%).
Conclusions. Pretreatment with pantoprazole suppresses H. pylori but does not impair the efficacy of a consecutive short-term, low-dose triple therapy.     

The Ideal Therapy Must Be Def ined in Each Geographical Area: Experience with a Quadruple Therapy in Spain

Background. Multiple therapeutic combinations have been tested to determine the optimal regimen(s) for Helicobacter pylori eradication, leading to very different results depending on the geographical area. Our goal was to evaluate the efficacy of a "quadruple" therapy with omeprazole, tetracycline, bismuth and metronidazole in our area.
Materials and Methods. We investigate 106 consecutive patients with active peptic ulcer disease (duodenal, gastric or both) and Helicobacter pylori infection. One-week therapy with omeprazole 20 mg b.i.d., tetracycline hydrochloride 500 mg q.i.d., colloidal bismuth subcitrate 120 mg q.i.d., and metronidazole 250 mg t.i.d was prescribed. Between the days 30 and 40 after treatment ended follow-up endoscopy was performed. Eradication was defined as both negative urease test and histology. Between days 90 and 360 a ¹³C urea breath test was performed in 100 patients.
Results. Of the 106 patients in the study, 91 had duodenal ulcer, 12 had gastric ulcer, and 3 had both. Side effects were observed in 25% of the cases. Eradication was achieved in 87.7% (93/106; CI 79.9–93.3). Healing was obtained in 95.2% (100/105; CI 89.2–98.4); 97.8% (CI 92.4–99.7) in those eradicated and 75% (CI 42.8–94.5) in non-eradicated ( p < .01).
Conclusions. Quadruple therapy with omeprazole, tetracycline, bismuth subcitrate and metronidazole achieves healing rates up to 95–100%. The 87.7% eradication rate obtained suggests that the regimen we used is a reasonable therapeutic alternative in our area.     

Double-blind, Multicenter, Placebo-Controlled Evaluation Of Clarithromycin And Omeprazole For Helicobacter Pylori-Associated Duodenal Ulcer

Background. Eradication of Helicobacter pylori leads to faster ulcer healing and a significant decrease in ulcer recurrence. Clarithromycin is the most effective monotherapy for eradicating H. pylori from the gastric mucosa, and omeprazole frequently is used for the treatment of duodenal ulcer disease, prompting the interest to investigate rigorously the combination of clarithromycin and omeprazole for eradicating H. pylori. Materials and Methods. The aim of this double-blind, randomized, multicenter (n=30), multinational (n=10) study was to compare clarithromycin and omeprazole with omeprazole monotherapy for the eradication of H. pylori from the gastric mucosa, endoscopic healing, and reduction of symptoms and ulcer recurrence in patients with active duodenal ulcer. Patients with active duodenal ulcer associated with H. pylori infection were randomized to receive omeprazole, 40 mg every morning for 14 days, with either clarithromycin, 500 mg, or placebo three times daily, which was followed by omeprazole, 20 mg every morning for 14 days. Patients underwent endoscopy before enrolling in the study, immediately after finishing treatment, and at 4- to 6-week and 6-month follow-up evaluations or at the recurrence of symptoms. Results. Two hundred and eight patients with active duodenal ulcer associated with confirmed H. pylori infection were randomized to treatment with either clarithromycin and omeprazole (n=102) or omeprazole and placebo (n=106). Four to six weeks after treatment was completed, H. pylori was eradicated in 74% (95% confidence interval, 63.0%–82.4%) of patients receiving clarithromycin and omeprazole, compared with 1% (0.0%–6.2%) of patients receiving omeprazole monotherapy (p < .001). Clarithromycin resistance developed in eight patients treated with clarithromycin and omeprazole and in none given omeprazole and placebo. Ulcers, which were healed following treatment in more than 95% of study patients, recurred by the 6-month follow-up visit in 10% (5%–19%) of dual therapy recipients, compared with 50% (39%–61%) of those who took omeprazole alone (p <.001). Conclusion. Clarithromycin and omeprazole dual therapy is simple and well-tolerated and leads to consistently high eradication rates for patients with duodenal ulcer associated with H. pylori infection.     

Double-Blind, Multicenter Evaluation of Lansoprazole and Amoxicillin Dual Therapy for the Cure of Helicobacter pylori Infection

Background Treatment with amoxicillin plus omeprazole results in disappointing cure rates of Helicobacter pylori infection. The minimal inhibitory concentration of lansoprazole for H. pylori in vitro is lower than that for omeprazole, prompting interest in treatment with amoxicillin plus lansoprazole.
Materials and Methods. H. pylori -infected patients with endoscopically documented duodenal ulcer either currently or within the past year were randomized to 14 days of (1) lansoprazole, 30 mg bid, plus amoxicillin, 1 gm tid; (2) lansoprazole, 30 mg tid, plus amoxicillin, 1 gm tid; (3) lansoprazole, 30 mg tid alone; or (4) amoxicillin, 1 gm tid alone. Endoscopy was done at enrollment and at 4 to 6 weeks after completion of treatment or for recurrent symptoms. H. pylori status was assessed by culture and histology. Ulcer prevalence was evaluated at follow-up endoscopy.
Results. Two hundred sixty-two patients met enrollment criteria and were treated. By per-protocol analysis, H. pylori infection was cured in 57% of those treated with lansoprazole twice daily plus amoxicillin and in 67% of those treated with lansoprazole three times daily plus amoxicillin, compared with 0% treated with lansoprazole alone or amoxicillin alone ( p < .001 for dual therapy versus either monotherapy). Amoxicillin resistance was not observed. At follow-up endoscopy, ulcer prevalence was 17% in patients treated with lansoprazole twice daily plus amoxicillin, 23% in those treated with lansoprazole three times daily plus amoxicillin, 33% in those treated with lansoprazole alone, and 35% in those treated with amoxicillin alone ( p = .024; lansoprazole twice daily plus amoxicillin versus amoxicillin alone).
Conclusions. Treatment with amoxicillin plus lansoprazole, 30 mg tid, led to cure of H. pylori infection in 67% of patients with active or recently healed duodenal ulcer.     

Helicobacter pylori. One bacterium and a broad spectrum of human disease! An overview.

Since the historical rediscovery of gastric spiral Helicobacter pylori in the gastric mucosa of patients with chronic gastritis by Warren and Marshall in 1983, peptic ulcer disease has been largely viewed as being of infectious aetiology. Indeed, there is a strong association between the presence of H. pylori and chronic active gastritis in histology. The bacterium can be isolated in not less than 70% of gastric and in over 90% of duodenal ulcer patients. Eradication of the organism has been associated with histologic improvement of gastritis, lower relapse rate and less risk of bleeding from duodenal ulcer. The bacterium possesses several virulence factors enabling it to survive the strong acid milieu inside the stomach and possibly damaging host tissues. The sequence of events by which the bacterium might cause gastric or duodenal ulcer is still not fully elucidated and Koch's postulates have never been fulfilled. In the majority of individuals, H. pylori infection is largely or entirely asymptomatic and there is no convincing data to suggest an increase in the prevalence of peptic ulcer disease among these subjects. An increasingly growing body of literature suggests an association between colonization by H. pylori in the stomach and a risk for developing gastric mucosa-associated lymphoid tissue (MALT), MALT lymphoma, gastric adenocarcinoma and even pancreatic adenocarcinoma. The bacterium has been implicated also in a number of extra-gastrointestinal disorders such as ischaemic heart disease, ischaemic cerebrovascular disease, atherosclerosis, and skin diseases such as rosacea, but a causal role for the bacterium is missing. Eradication of H. pylori thus seems to be a beneficial impact on human health. Various drug regimens are in use to eradicate H. pylori involving the administration of three or four drugs including bismuth compounds, metronidazole, clarithromycin, tetracyclines, amoxycillin, ranitidine, omeprazole for 1-2 weeks. The financial burden, side effects and emergence of drug resistant strains due to an increase in the use in antibiotics for H. pylori eradication therapy need further reconsideration.     

Pretreatment antimicrobial susceptibilities of paired gastric Helicobacter pylori isolates: antrum versus corpus

Background. Antimicrobial susceptibility testing of Helicobacter pylori isolates is the most useful tool for guiding specific therapy, especially when primary resistance is suspected. However, the most informative gastric biopsy site for detection of resistant H. pylori isolates is uncertain. We sought to determine whether susceptibilities to commonly used antimicrobials (amoxicillin, clarithromycin, minocycline, and metronidazole) were related to biopsy site.
Methods. H. pylori isolates were obtained from patients who had duodenal ulcer and had not received any therapy directed against H. pylori. Agar-dilution minimum inhibitory concentrations of each antimicrobial were compared between paired H. pylori isolates from the antrum and the proximal corpus.
Results. Differences in minimum inhibitory concentrations exceeding twofold were observed within the pairs of H. pylori isolates in 5 of the 40 patients tested. In three patients with clarithromycin-resistant isolates and two with metronidazole-resistant isolates, both antral and corporeal specimens revealed resistance. However, no patient had pairs of isolates categorized as resistant at one site and sensitive at the other.
Conclusions. While we found that an individual may have a mixed H. pylori infection with respect to differing antimicrobial susceptibility in different parts of the stomach, a single biopsy specimen from either the antrum or the corpus should provide reliable detection of H. pylori isolates with primary resistance.     

The prevalence of peptic ulcer not related to Helicobacter pylori or non-steroidal anti-inflammatory drug use is negligible in southern Europe

BACKGROUND AND AIM: Helicobacter pylori is the major cause of peptic ulcer disease, but the proportion of H. pylori-negative peptic ulcers seems to be increasing in developed countries. We investigated the frequency of H. pylori-negative peptic ulcer without intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in a Mediterranean European country. MATERIALS AND METHODS: We prospectively collected consecutive patients with an endoscopically verified active peptic ulcer over 6 months from different areas of Spain. Helicobacter pylori infection was assessed by rapid urease test and histologic examination (corpus and antral biopsies). A (13)C-urea breath test was performed if H. pylori was not detected with the invasive test. Patients were considered H. pylori-negative if all three tests were negative. NSAID use was determined by structured data collection. RESULTS: Of 754 consecutive peptic ulcer patients, 16 (2.1%) were H. pylori-negative and had not used NSAIDs before the diagnosis. Of the 472 patients who had duodenal ulcers, 95.7% (n = 452) were H. pylori-positive and only 1.69% (n = 8) were negative for both H. pylori infection and NSAID use; 193 patients had benign gastric ulcers and 87% (n = 168) of them were infected by H. pylori (p <.001 vs. duodenal ulcers). NSAID intake was more frequent in gastric ulcer patients (52.8%) than in duodenal ulcer patients (25.4%; p <.001). Consequently, the frequency of H. pylori-negative gastric ulcer in patients not using NSAID was 4.1% (n = 8). CONCLUSION: Peptic ulcer disease is still highly associated with H. pylori infection in southern Europe, and only 1.6% of all duodenal ulcers and 4.1% of all gastric ulcers were not associated with either H. pylori infection or NSAID use.     

Four-day, twice daily, quadruple therapy with amoxicillin, clarithromycin, tinidazole and omeprazole to cure Helicobacter pylori infection: a pilot study

Background. The best regimen for the treatment of Helicobacter pylori infection has yet to be defined. Four-day quadruple therapy with tetracycline, metronidazole, bismuth, and a proton pump inhibitor has been shown to obtain a very high cure rate. However, the fact that it must be taken four times daily may interfere with compliance. The objective of the study was to test the efficacy and tolerability of a new 4-day therapy with 4 drugs taken every 12 hours to cure H. pylori infection.
Patients and Methods. Fifty-six consecutive patients with peptic ulcer disease and H. pylori infection were treated with an oral 4-day course with omeprazole (20 mg/12 hours), clarithromycin (500 mg/12 hours), amoxicillin (1 g/12 hours) and tinidazole (500 mg/12 hours). Efficacy of the treatment was determined at least 2 months after therapy either by biopsy (in the case of gastric ulcer) or by ¹³C-urea breath test. A second breath test was performed at least 6 months after therapy.
Results. Two patients were lost to follow-up. Forty-nine of the remaining 54 patients were cured at the first control [intention-to-treat cure rate: 87.5% (CI 95% 75–94%); per protocol cure rate: 90.7% (CI 95% 81–98%)]. Forty-three of these 49 cured patients returned for a second ¹³C urea breath-test at 6–12 months. Two of them were not cured, giving a long-term cure rate of 85.5% per protocol and 73.2% by intention-to-treat. Compliance was good, although 25 patients had mild side effects.
Conclusion. This particular four-day therapy is well tolerated, easy to follow, and achieves an acceptably high cure rate.     

Immediate endoscopy or initial Helicobacter pylori serological testing for suspected peptic ulcer disease: estimating cost-effectiveness using decision analysis.

OBJECTIVE: To compare the clinical and economic effects of a strategy using immediate endoscopy to a non-invasive strategy utilizing a serologic test for Helicobacter pylori infection for individuals with symptoms suggestive of peptic ulcer disease. DESIGN: Cost-effectiveness analysis evaluating the clinical and economic effects of alternative management strategies of hypothetical patients with suspected peptic ulcer disease in a computer simulation model. INTERVENTION: Two strategies for hypothetical patients with suspected ulcer disease were evaluated: 1) Immediate endoscopy and biopsy for H. pylori, using antisecretory treatment in all patients with documented ulcers and adding antibiotic eradication therapy for those patients with ulcers whose biopsies were positive for H. pylori. 2) Empiric treatment with antisecretory therapy and serologic testing for H. pylori for all patients, using antibiotic eradication therapy only in patients testing positive for H. pylori. MEASUREMENTS: Cost per ulcer cured over a one-year study period. RESULTS: The more cost-effective strategy was the test-and-treat strategy (Strategy 2) with $4481 cost per ulcer cured. The immediate endoscopy strategy resulted in $8045 cost per ulcer cured. The cost-effectiveness advantage of the non-invasive strategy diminished as the cost of endoscopy fell or as the probability of recurrent symptoms rose in patients initially managed without endoscopy. CONCLUSION: Endoscopy, though costly, precisely guided diagnosis and treatment and, thus, potentially reduced the number of patients inappropriately treated. However, cost-effectiveness analysis supports the continued practice of initial non-invasive management of patients with symptoms suggestive of peptic ulcer disease, achieving the benefits of H. pylori eradication through the use of serologic testing to guide antibiotic use.     

Resistance to medical ulcer therapy--possible reasons and management.

In 112 patients with duodenal ulcer (males, mean age 29, range 18-35) with a history of at least 3 years, and never being treated with H2-antagonists, maintenance therapy with Tagamet was started. All of them had ulcer recurrence when entering the study. The first two months a full dose was applied, after this bedtime doses up to 24 months. Endoscopy was performed at the beginning, after the first and second months and then every two-month period. Gastric secretion was measured every 2-3 months. A resistant ulcer was defined as one 1/not healing within the two initial months, 2/recurring on maintenance treatment. RESULTS: in 78% the ulcer was healed within one month, in 96% within two months, in the rest within the following 3-4 weeks. Relapses occurred in 21 patients, altogether 27 times. Factors likely to contribute to recurrence included a large ulcer size, longer duration, an inflamed mucosa and--most frequently--heavy smoking. Patients with relapses had higher initial secretory values and smaller decrease during maintenance treatment. Helicobacter pylori (examined in a subgroup) was not clearly associated with ulcer recurrence.