Pylori-related Diseases Research Articles

4-day triple therapy with rabeprazole, amoxicillin and clarithromycin in the eradication of Helicobacter pylori in patients with peptic ulcer disease--A pilot study.

It is well established that a 7-day triple therapy achieves eradication rates of Helicobacter pylori between 90% and 95%. Due to a lack of highly effective short-term eradication studies the aim of the present pilot study was to investigate the effect of a 4-day triple therapy with the new proton pump inhibitor rabeprazole (20 mg b. i. d.) in combination with clarithromycin (500 mg b. i. d.) and amoxicillin (1 g b. i. d.) without acid-suppressive pre-treatment in patients with H. pylori-related peptic ulcer disease. 20 patients (11 men, 9 women) with endoscopically diagnosed peptic ulcers (gastric ulcer: n = 5; duodenal ulcer: n = 9; combined gastric and duodenal ulcer: n = 2, gastric or duodenal ulcer scars: n = 4) and H. pylori infection were consecutively recruited. The Helicobacter pylori status was assessed by means of histology, CLO (urea-) test and C13-urea breath test (C13-UBT) at entry. Treatment success was determined by C13-UBT 35-42 days after end of treatment. In 18 out of the 20 patients (90%) [77-100%, 95%-CI] a negative test result was found in C13-UBT 35-42 days after treatment. The 2 patients who remained H. pylori-positive had a duodenal ulcer. A 4-day triple therapy of rabeprazole in combination with clarithromycin and amoxicillin seems to be highly effective in eradicating H. pylori and well tolerated in patients with gastric and duodenal ulcer disease. The achieved eradication rate of 90% is comparable with the established 7-day triple therapy regimens. On the basis of these results and considering costs, side effects and compliance a large number of patients should be enrolled in a confirmatory 4-day eradication trial.

Inducible Nitric Oxide Synthase Expression in Gastroduodenal Diseases Infected with Helicobacter pylori

Nitric oxide (NO) is synthesized enzymatically from L-arginine by NO synthase, which is measured by inducible NO synthase (iNOS). Helicobacter pylori (H. pylori) infection produces a state of chronic immunostimulation in the gastric epithelium. Infection with cagA+ H. pylori has greater degree of gastric inflammation and epithelial cell damage. Therefore, we compared the levels of iNOS in patients with H. pylori infection in relation to cagA status and H. pylori-related disease. One hundred and seven patients, including 51 patients with gastric cancer, 12 patients with gastric ulcer, 18 patients with duodenal ulcer and 26 patients with chronic gastritis, were enrolled in this study. Biopsies from the antrum and body were obtained for histologic examination, culture and reverse transcriptionase-PCR (RT-PCR) for detection of iNOS gene expression. The presence of H. pylori was confirmed by Giemsa staining or culture and the gene expression of cagA in H. pylori isolates was confirmed by PCR. H. pylori infection was detected in 70.1% (75/107) and cagA was detected in 84.8% (28/33). iNOS expression was detected in 49.5% (53/107) and there was no significant difference in iNOS expression according to H. pylori infection nor the cagA status in the gastroduodenal diseases. However, iNOS expression was more frequently detected in gastric cancer than the other H. pylori-related diseases (64.7% vs. 35.7%, p <.05). Although NO was thought be involved in the gastric carcinogenesis, the level of NO production was not related to H. pylori infection or cagA status.

Helicobacter pylori infection in Korea.

Helicobacter pylori is a gram-negative bacterium that was first isolated in 1982. Since then, H. pylori infection in humans has been shown to be associated with gastritis, peptic ulcer disease, gastric carcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma as well. The epidemiology, transmission, and pathogenicity of H. pylori has been a subject of intensive study. Successful treatment improves the cure rate of peptic ulcerations and treatment with antimicrobials also decreases the recurrence rate of these diseases. Better regimens having less toxicity and a good eradication rate have also been developed. A better understanding of the pathophysiologic mechanisms relating to H. pylori induced mucosal damages would result in more options for the prevention of peptic ulcers and carcinogenesis. Korea has a relatively high incidence of H. pylori infection and gastric cancer. Growing interest has developed in view of its importance in being associated with various gastroduodenal diseases. Furthermore, along with a high incidence of H. pylori-related disease in Korea, because the interaction between H. pylori, host factors and environmental factors is important in disease pathogenesis, we need to have precise data on the characteristics of H. pylori-related diseases that occur in Korea. In the present report we review the epidemiology, transmission route, diagnosis, pathogenesis, treatment methods and relationship with gastroduodenal diseases with in special references to basic and clinical data that have been published.

Testing for Helicobacter pylori in the clinical setting.

There are a variety of tests available to identify Helicobacter pylori infection. These tests can be divided into those that do not require and those that do require endoscopy. This review provides a detailed discussion of the available diagnostic tests for H. pylori infection. Special attention is paid to the role of diagnostic testing in the management of patients with H. pylori-related disease. The potential advantages and disadvantages of various tests and the role of testing to confirm eradication after treatment for H. pylori is also discussed.

Helicobacter pylori-related extradigestive diseases and effects of eradication therapy

Helicobacter pylori-related extradigestive diseases and effects of eradication therapy

Expression and Binding Analysis of GST-VacA Fusions Reveals That the C-Terminal ∼100-Residue Segment of Exotoxin Is Crucial for Binding in HeLa Cells

The Helicobacter pylori toxin VacA induces intracellular vacuolation and plays an essential role in H. pylori-related diseases. The mature exotoxin is divided into two domains, P37 and P58. A soluble form of VacA fused with GST was expressed in Escherichia coli. Although the soluble fusion lacked vacuolating activity after cleavage by thrombin, it had a binding affinity similar to that of the native VacA. Moreover, it blocked the vacuolating activity induced by the native toxin. Different C-terminal truncated fusions were generated (GST-P72, GST-P53, and GST-P37) and were also produced in a soluble form. A significantly reduced binding activity was seen for GST-P72 and nearly no specific association was detected for GST-P37. Our results suggested that the whole P58 fragment contributed to the cell binding activity in HeLa cells, particularly in the C-terminal ∼100-residue region.

VIRULENCE AND PATHOGENICITY OF HELICOBACTER PYLORI

Bacterial and host response factors play significant roles in the pathogenicity of H. pylori-related disease manifestations. The complete DNA sequences for two H. pylori strain genomes have been published. The differences in the sequences between these two unrelated strains may enable clinicians to identify rapidly other conserved and potentially virulent genes and products. Whether these two DNA sequences are sufficient representation of the H. pylori genetic heterogeneity is unknown. The host immune response and the cascade of events that occurs with H. pylori infection are being clarified rapidly. Understanding the role of this gastric bacterium in apoptosis and cellular proliferation would enable clinicians to understand its relationship to ulcerogenesis and gastric malignancy. Piecing together many observations related to H. pylori would result in understanding the interaction of H. pylori factors and host responses that lead to the variety of disease manifestations associated with this chronic infection. The development of animal models with H. pylori and other Helicobacter species has set the stage in which in vitro observations can be tested in the in vivo model.

Heliobacter Pylori and Non-ulcer Dyspepsia.

There is no definitive therapy for this disorder. Heliobacter pylori eradication therapy is only useful in areas with a high prevalence of H. pylori-related ulcer disease Proton pump inhibitors are effective in short-term treatment for dyspepsia with a predominant symptom of epigastric pain Prokinetic agents may be useful in some patients, particularly those with dysmotility-like dyspepsia, but serious side effects limit their usefulness.

Helicobacter pylori vacA genotypes and cagA gene in a series of 383 H. pylori-positive patients.

Only 10-15% of all patients infected with Helicobacter pylori develop peptic ulcer disease (PUD) or gastric cancer. Apart from immunological factors in the host, virulence determinants of H. pylori such as the vacuolating cytotoxin (VacA) or the cytotoxin-associated protein A (CagA) might represent a predisposition for the development of PUD. We studied antral biopsies of 383 H. pylori-positive patients with peptic ulcer disease (PUD) or other H. pylori-related diseases for H. pylori vacA genotypes and the presence of the cagA gene by PCR. VacA genotypes and cagA status could be completely determined in 357 (93.2%) of the patients. In 91 (93.8%) of 97 patients with PUD, the vacA s1 genotype (s1m1, 45; s1m2, 46 patients) was present. The vacA s2m2 genotype was found in only 6 (6.2%) of 97 patients with PUD. In contrast, 180 (75.3%) of 239 patients (s1m1, 89; s1m2, 91 patients) without PUD and without gastric malignancies harbored strains with the vacA s1 genotype. The vacA genotype s2m2 was found in 59 (24.7%) of these patients. The presence of the cagA gene was closely associated with the vacA genotype s1 and found in 124 (88.6%) and in 113 (80.7%) of patients with the s1m1 or s1m2 genotypes, respectively, whereas strains with the genotype s2m2 were almost exclusively cagA negative. Most H. pylori strains found in patients with PUD possess the vacA s1 genotype and the cagA gene. Patients with this type of H. pylori strain but without PUD might be at higher risk of developing PUD. In contrast, the risk for PUD might be significantly decreased in those patients who are infected by H. pylori strains with the vacA s2 genotype lacking the cagA gene.

Risk factors for presentation with bleeding in patients with Helicobacter pylori-related peptic ulcer diseases.

At present, there is no study that simultaneously addresses the apparent differences between bacterial and host factors in patients with bleeding and nonbleeding Helicobacter pylori-related ulcer diseases. Therefore, we designed this prospective study to evaluate whether there are identifiable differences between the two groups of patients whose H. pylori-related peptic ulcer diseases present with bleeding or dyspepsia. From July 1996 to November 1996, consecutive patients presenting with upper gastrointestinal bleeding or dyspepsia were enrolled if H. pylori-related ulcer diseases were confirmed. Fifteen clinical, endoscopic, histologic, and serologic factors were tested for association with ulcer bleeding by a logistic regression analysis. In the study period, bleeding occurred in 39 out of 119 patients with H. pylori-related peptic ulcer diseases. Multivariate analysis showed that ingestion of nonsteroidal antiinflammatory drugs (NSAIDs; p = 0.0156; odds ratio = 5:4), ulcer size > or = 1 cm (p = 0.0033; odds ratio = 4:2), and low bacterial density (p = 0.0030; odds ratio = 4:1) were independent factors associated with the risk of bleeding. There were no associations between ulcer bleeding and age, sex, smoking, alcohol consumption, the histologic grade of gastritis, location and number of ulcers, and the cytotoxin-associated gene (CagA) status of H. pylori strain. Therefore, we concluded that H. pylori-related ulcer patients who use NSAIDs or have large ulcers are more likely to present with upper gastrointestinal bleeding; that the CagA-bearing strains are not associated with the development of bleeding complication in patients with peptic ulcer diseases; and that the exact reason concerning the association between low bacterial density and ulcer bleeding merits further investigation.

Helicobacter pylori-related disease: guidelines for testing and treatment.

To develop practical guidelines for the treatment of patients with suspected and documented Helicobacter pylori-related gastroduodenal diseases. A panel of physicians with expertise in H. pylori reviewed, critically appraised, and synthesized the literature on assigned topics and presented their overviews to the panel. Consensus was obtained in controversial areas through discussion. The panel recommended testing for H. pylori in patients with active ulcers, a history of ulcers, or gastric mucosa-associated lymphoid tissue lymphomas. Young, otherwise healthy patients with ulcerlike dyspepsia and those with a family history or fear of gastric cancer may also undergo H pylori testing. Non-endoscopic methods are preferred for H. pylori diagnosis. Dual medication regimens should not be used for therapy; twice-daily triple therapy with a proton pump inhibitor or ranitidine bismuth citrate, clarithromycin, and amoxicillin for 10 to 14 days is an appropriate therapy. Posttreatment assessment of H. pylori status using urea breath testing should be considered in patients with a documented history of ulcer disease or with persistent symptoms.

No association between HLA-DRB1 and helicobacter pylori related diseases found

No association between HLA-DRB1 and helicobacter pylori related diseases found

Disease-specific Helicobacter pylori virulence factors: the unfulfilled promise.

A number of putative virulence factors for Helicobacter pylori have been identified including cagA, vacA and iceA. The criteria for a true virulence factor includes meeting the tests of biologically plausibility with the associations being both experimentally and epidemiologically consistent. Although disease-specific associations have been hypothesized/claimed, there are now sufficient data to conclusively state that none of these putative virulence factors have disease specificity. CagA has been claimed to be associated with increased mucosal IL-8 and inflammation, increased density of H. pylori in the antrum, duodenal ulcer (DU), gastric cancer, and protection against Barrett's cancer. Only the increase in IL-8/inflammation is direct and substantiated. Different H. pylori strains with functional cag pathogenicity islands do not vary in virulance as it has been shown that mucosal IL-8 levels are proportional to the number of cagA + H. pylori independent of the disease from which the H. pylori were obtained. It is now known that the density of either cagA + and cagA-H. pylori in the antrum of patients with H. pylori gastritis is the same. In contrast, the mean density of H. pylori in the antrum in DU is greater than in the antrum of patients with H. pylori gastritis. Of interest, the density of H. pylori is higher in the corpus of patients with H. pylori gastritis than those with DU, suggesting that acid secretion plays a critical role in these phenomena. The presence of a functional cag pathogenicity island increases inflammation and it is likely that any factor that results in an increase in inflammation also increases the risk of a symptomatic outcome. Nevertheless, the presence of a functional cag pathogenicity island has no predictive value for the presence, or the future development of a clinically significant outcome. The hypothesis that iceA has disease specificity has not been confirmed and there is currently no known biological or epidemiological evidence for a role for iceA as a virulence factor in H. pylori-related disease. The claim that vacA genotyping might prove clinically useful, e.g. to predict presentation such as duodenal ulcer, has been proven wrong. Analysis of the worldwide data show that vacA genotype s1 is actually a surrogate for the cag pathogenicity island. There is now evidence to suggest that virulence is a host-dependent factor. The pattern of gastritis has withstood the test of time for its relation to different H. pylori-related diseases (e.g. antral predominant gastritis with duodenal ulcer disease). The primary factors responsible for the different patterns of gastritis in response to an H. pylori infection are environmental (e.g. diet), with the H. pylori strain playing a lesser role. Future studies should work to eliminate potential bias before claiming disease associations. Controls must exclude regional or geographic associations related to the common strain circulation and not to the outcome. The authors must also control for both the presence of the factor and for the disease association. The study should be sufficiently large and employ different diseases and ethnic groups for the results to be robust. The findings in the initial sample (data derived hypothesis) should be tested in a new group (hypothesis testing), preferably from another area, before making claims. Finally, it is important to ask whether the results are actually a surrogate for another marker (e.g. vacA s1 for cagA) masquerading for a new finding. Only the cag pathogenicity island has passed the tests of biological plausibility (increased inflammation) and experimental and epidemiological consistency.

H. pylori in the pathogenesis of duodenal ulcer: interaction between duodenal acid load, bile, and H. pylori

OBJECTIVE: Helicobacter pylori (H. pylori) growth is inhibited by bile yet it can grow in the duodenal bulb and cause ulcer disease. The aim of this study was to test the effect of bile on H. pylori viability and growth and to determine whether acidification of bile reduces its inhibitory activity. METHODS: Fresh human bile was collected at laparotomy and tested for inhibitory activity of H. pylori using broth dilution assays. Six clinical isolates of H. pylori obtained from patients with duodenal ulcer were used for each experiment. The bile was diluted from 1:3 to 1:192; its inhibitory effect on H. pylori was tested before and after acidification, treatment with cholestyramine, or chloroform. Bile was acidified to a pH of 2–6, centrifuged at 8000 rpm for 20 min to remove precipitated bile acids, and the supernatant pH readjusted. Controls included BHI broth without bile (positive control) and bile that was acidified to pH 2 and neutralized without centrifugation. RESULTS: Human bile inhibited H. pylori growth in a dose dependent manner. Growth of all strains was supported for all strains only at a dilution of 1:192. In contrast, after acidification to pH ≤5 and centrifugation to remove precipitated bile acids, all strains grew at a bile dilution of 1:12. Neither chloroform extraction of lipids, nor acidification without centrifugation removed the inhibitory action of bile. In contrast, cholestyramine sequestration of bile acids completely removed all inhibitory activity. CONCLUSIONS: The duodenal acid load may be the critical factor to explain the ability of H. pylori to colonize the duodenal bulb by precipitating glycine-conjugated bile salts. The combination of a high duodenal acid load and H. pylori infection is likely the critical event in the pathogenesis of H. pylori-related duodenal ulcer disease.

H. pylori in the pathogenesis of duodenal ulcer: interaction between duodenal acid load, bile, and H. pylori.

Helicobacter pylori (H. pylori) growth is inhibited by bile yet it can grow in the duodenal bulb and cause ulcer disease. The aim of this study was to test the effect of bile on H. pylori viability and growth and to determine whether acidification of bile reduces its inhibitory activity. Fresh human bile was collected at laparotomy and tested for inhibitory activity of H. pylori using broth dilution assays. Six clinical isolates of H. pylori obtained from patients with duodenal ulcer were used for each experiment. The bile was diluted from 1:3 to 1:192; its inhibitory effect on H. pylori was tested before and after acidification, treatment with cholestyramine, or chloroform. Bile was acidified to a pH of 2-6, centrifuged at 8000 rpm for 20 min to remove precipitated bile acids, and the supernatant pH readjusted. Controls included BHI broth without bile (positive control) and bile that was acidified to pH 2 and neutralized without centrifugation. Human bile inhibited H. pylori growth in a dose dependent manner. Growth of all strains was supported for all strains only at a dilution of 1:192. In contrast, after acidification to pH < or =5 and centrifugation to remove precipitated bile acids, all strains grew at a bile dilution of 1:12. Neither chloroform extraction of lipids, nor acidification without centrifugation removed the inhibitory action of bile. In contrast, cholestyramine sequestration of bile acids completely removed all inhibitory activity. The duodenal acid load may be the critical factor to explain the ability of H. pylori to colonize the duodenal bulb by precipitating glycine-conjugated bile salts. The combination of a high duodenal acid load and H. pylori infection is likely the critical event in the pathogenesis of H. pylori-related duodenal ulcer disease.

Is your stomach bugging you?: The rise and fall of the bacterium H. pylori

The chapter of medicine that describes the bacterium Helicobacter pylori is a tale of a few individuals taking a stand against the medical wisdom of their day. The once-improbable suggestion that a bacterial infection can cause ulcers is now dogma. Yet a maverick is now arguing that H. pylori may have some benefits as well, and so he warns that a wholesale campaign to eradicate the bacterium is premature. Proving that this bacterium is responsible for ulcers was no small task. Until the 1980s, most physicians believed that high acid concentration in the stomach, stress, and spicy foods were the agents behind ulcers. Nevertheless, Barry J. Marshall and Robin Warren, physicians in Perth, Australia, became convinced that bacteria underlie the problem. They isolated what they believed to be the culprit in 1982. Over the next decade, Marshall and a few colleagues convinced gastroenterologists around the world that H. pylori is the leading cause of stomach ulcers. At least a third to half of people worldwide are infected with H. pylori, although most infected people have no symptoms. The frequency of infection varies from country to country. In most developing nations, from 70 to 90 percent of adults harbor the microbe, probably from early childhood. In developed countries, fewer than 10 percent of children become infected, but generally, about 50 percent of 60-year-olds carry the bacterium. For a small fraction of those who are infected, the consequences can be deadly. The microbe has been linked to stomach, or gastric, cancer, a leading killer worldwide. In their lives, I to 3 percent of people infected with H. pylori will develop stomach cancer-a risk up to six times that faced by uninfected people. The bacterium also seems to trigger a much less common malignancy, mucosaassociated lymphoid-tissue lymphoma. This is a cancer of white blood cells found near the stomach lining. In 1994, the World Health Organization classified the bacterium as a carcinogen. In the United States each year, some 7 million people suffer H. pylori-related disease, including ulcers, and thousands die, primarily from gastric cancer. Antibiotics can cure ulcers, and even some cases of the lymphoma. In 1995, the Digestive Health Initiative, organized by the American Gastroenterological Association and other organizations, launched a campaign to convince consumers and physicians that people having ulcer symptoms should be tested for H. pylori. Since then, according to the initiative, the proportion of physicians ready to treat H. pylori has risen dramatically. Just as gastroenterologists are beginning to smell success in their quest to eliminate the ulcer-causing microbe, however, an investigator who has studied H. pylori for many years is trying to convince researchers and physicians that the elimination of the microbe may not be such a good idea. Martin Blaser of Vanderbilt University in Nashville says that the bacterium's presumed long acquaintance with mankind may offer benefits. His preliminary evidence suggests that people who aren't infected with H. pylori are more likely to develop reflux-a painful disease in which acid from the stomach backs through a leaky valve and inflames the esophagus. The bacterium may also reduce the risk of the cancer of the esophagus, he says. In the long run, eliminating H. pylori may trade one cancer risk for another, Blaser contends. Still, other physicians point out that esophageal cancer is rare, whereas stomach cancer is the 14thleading cause of cancer death worldwide.

Contribution of major histocompatibility complex genes to susceptibility and resistance in Helicobacter pylori related diseases.

Although there have been numerous reports concerning the virulence factors of isolates for investigating the pathogenesis of Helicobacter pylori infection, few studies have been carried out regarding the association of HLA class II genes of the host with H. pylori related diseases. Two published studies have only analysed the HLA DQ locus alone. The aim of this study was thus to determine the association of HLA class II genes (DR, DQ and DP) with H. pylori related diseases using the DNA typing method. Fifty-eight patients with H. pylori positive gastric ulcers, 44 patients with H. pylori positive duodenal ulcers, 45 patients with H. pylori positive gastritis and 34 healthy subjects without H. pylori infection were typed for HLA class II genes by means of DNA typing with the polymerase chain reaction-sequence specific oligonucleotide probes method. A negative association with DRB1*1501, DQA1*01021 and DQB1*0602 alleles was noted in all three of the patient groups studied. Compared with the healthy controls, a positive association with DPA1*0201 (P= 0.032) and DPB1*0901 (P=0.005) in gastric ulcers, a positive association with DRB1*0405 (P=0.022) and DQB1*0401 (P=0.044) in duodenal ulcers, and a positive association with DPB1*0901 (P=0.016) in gastritis were observed. A haplotype analysis showed that the association of alleles with H. pylori related disease was with the haplotype rather than with either of the alleles individually. After correction for multiple comparisons, all the significant associations obtained between H. pylori related diseases and HLA class II genes disappeared. The interplay between host immunogenetic factors, bacterial virulence factors and environmental conditions may thus play a more important role in the outcome of H. pylori infection than immunogenetic factors alone.

Sequence anomalies in the Cag7 gene of the Helicobacter pylori pathogenicity island.

The severity of Helicobacter pylori-related disease is correlated with a pathogenicity island (the Cag region of about 26 genes) whose presence is associated with the up-regulation of an IL-8 cytokine inflammatory response in gastric epithelial cells. Statistical analysis of the Cag gene sequences calculated from the complete genome of strain 26695 revealed several unusual features. The Cag7 sequence (1,927 aa) has two repeat regions. Repeat region I runs 317 aa in a form of AAA proximal to the protein N terminal; repeat region II extends 907 aa in the middle of the protein sequence consisting of 74 contiguous segments composed from selections among six consensus sequences and includes 58 regularly distributed cysteine residues with consecutive cysteines mostly 12, 18, or 24 aa apart. This "regular" cysteine arrangement may provide a scaffolding of linker elements stabilized by disulfide bridges. When Cag7 homologues from different strains are compared, differences were found almost exclusively in the repeat regions, resulting from deletion and/or insertion of repeating units. These observations suggest that the anomalous repetitive structure of the sequence plays an important role in the conformation of Cag7 gene product and potentially in the function of the pathogenicity island. Other facets of the Cag7 sequence show significant charge clusters, high multiplet count, and extremes of amino acid usage.

Helicobacter pylori Infection in a Large Company

The Authors Reply: We appreciate Dr Ziem's interest in our health initiative to identify and treat Helicobacter pylori-related disease among BASF employees in Ludwigshafen, Germany. Dr Ziem discusses observations from her own clinical experience and proposes assessment of secretory IgA (s-IgA) in individuals with positive and negative IgG serology against H. pylori to improve our understanding of the interaction between chemical exposure and infectious illnesses. The potential role of s-IgA in the immunopathology of H. pylori infection is presently unclear.1,2 Because measurement of specific s-IgA in sputum, serum, or gastric juice samples was not included in the protocol for this health initiative, we cannot provide the assessment requested. Members of our clinic attendee recruitment subgroup are employees with potential for exposure to industrial chemicals. Within this group of employees, we observed an H. pylori infection prevalence (40%), as determined by IgG serology, that was in general agreement with that seen in an unselected German population (39%).3 The prevalence of dyspepsia (13%) also did not differ greatly from dyspepsia prevalence rates in other nonpatient populations, which have ranged from 11% to 46%.4-6 To date, we have not seen evidence of either enhanced rates of infection or an unexpected prevalence of gastrointestinal symptoms in the BASF AG workforce in Ludwigshafen. Our health initiative includes follow-up components that should enable a longitudinal assessment of the relationship between H. pylori infection and various gastrointestinal health end points, as well as an assessment of treatment success. Andreas Zober, MD, PhD Occupational Medical and Health; Protection Department; BASF AG; Ludwigshafen, Germany Dieter Schilling, MD Medical Clinic C of the Municipal; Clinic of Ludwigshafen GmbH; Ludwigshafen, Germany M. Gerald Ott, PhD Corporate Medical Department; BASF Corporation; Mt. Olive, NJ

One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based anti- Helicobacter triple therapy: a prospective randomized controlled trial

OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by the presence of metronidazole resistance. In vitro studies suggest that ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity against metronidazole resistant strains of Helicobacter pylori ( H. pylori). Whether this confers a superior clinical efficacy remains unproven. This study compared the efficacy of RBC-based triple therapy with bismuth triple therapy in eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease or gastritis were randomized to receive either 400/mg of RBC twice daily plus 400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and 500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole susceptibility was determined by the E-test and pretreatment resistance was defined as minimum inhibitory concentration ≥32/mg/L. RESULTS: Of 100 consecutive patients randomized, two patients were lost to follow-up in each group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant. Perprotocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%), respectively ( p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50 and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher eradication of metronidazole resistant H. pylori was observed in the RMT group (25 of 25, 100%) than in the BMT group (12 of 16, 75%), ( p = 0.018). Side effects observed in the two treatment groups were comparable. CONCLUSIONS: One week of RBC triple therapy with metronidazole and tetracycline is an effective anti- Helicobacter therapy. This regimen is more appropriate in areas of high prevalence of metronidazole resistance.