Treatment of Helicobacter pylori.

Triple therapy, consisting of two antibiotics, clarithomycin and amoxicillin or metronidazole in combination with a proton pump inhibitor (PPI) has become the first-line option for infection with Helicobacter pylori and has been recommended at several consensus conferences. In clinical practice, approximately 20% of patients will fail to obtain H. pylori eradication with the recommended treatment regimens. Major causes of treatment failure are insufficient patient compliance and antibiotic resistance. Because of antibiotic resistance, bismuth-based quadruple therapy has also become a first-line regimen in areas with exceedingly high rates of clarithromycin and metronidazole resistance, and is the preferred second-line option otherwise. Triple therapies based on levofloxacin and/or rifabutin mainly with combination of amoxicillin are options if multiple eradication failure occurs. However, following therapy failure beyond a second treatment attempt requires antibiotic resistance testing. New drugs and adjuvant agents have been reported but their efficacy needs further evaluation.

Diagnostics of Helicobacter pylori infection in patients with peptic ulcer bleeding.

BACKGROUND: In peptic ulcer bleeding, the sensitivity of H. pylori tests, in particular of the rapid urease test (RUT), has been reported to be insufficient. AIM: To validate the RUT, serology and the urea breath test were carried out in patients with bleeding peptic ulcers, and to study the influence of H. pylori suppressive treatment (HpSuT), i. e., antibiotics and proton pump inhibitors. PATIENTS AND METHODS: 123 consecutive patients (mean age 65.5 years) with a relevant bleeding from gastric or duodenal ulcers were prospectively tested for H. pylori infection by directs tests (RUT, histology, culture, urea breath test) and by IgG serology as an indirect test. Positive H. pylori status was defined by positive histology or culture. RESULTS: In patients without HpSuT during the preceding four weeks (N = 83), the sensitivity and specificity of RUT was 94 and 84 %, that of serology 83 and 68 % respectively. The sensitivity of urea breath test decreased from 82 to 60 % after even one day of HpSuT. In the overall group, the duration of HpSuT and preceding hospitalization were independent factors linked with negative results of all direct tests. CONCLUSIONS: In peptic ulcer bleeding, RUT combined with histology is an adequate diagnostic approach. However, false negative results have to be considered following even short-term HpSuT or hospitalization. Non-invasive diagnosis based on serology alone is inaccurate and should be complemented by the urea breath test prior to starting HpSuT.

Helicobacter pylori genotypes and expression of gastritis in erosive gastro-oesophageal reflux disease.

BACKGROUND: Epidemiological studies suggest a negative association between Helicobacter pylori and gastro-oesophageal reflux disease (GORD). Moreover, cagA-positive strains are reported to protect from complications of GORD. The aim of this study was to determine virulence factors (cagA, vacA and iceA) of H. pylori strains and the pattern of gastritis in patients with GORD in comparison with patients with duodenal ulcer (DU) or functional dyspepsia (FD). METHODS: H. pylori strains isolated from gastric biopsies of 105 consecutive patients with mild to moderate erosive GORD (n = 35, LA grade A-B), and from sex- and age-matched patients with DU (n = 35) or FD (n = 35 without reflux symptoms) were investigated. CagA, vacA, and iceA genotypes were determined by PCR analysis of the isolates. Gastritis was classified in accordance with the updated Sydney classification. RESULTS: The prevalence of all three H. pylori virulence factors was higher in patients with GORD (cagA+ 80%, vacA s1 77%, iceA1 71%) and DU (cagA+ 83%, vacA s1 80%, iceA1 74%) than in patients with FD (cagA+ 40%, vacA s1 49%, iceA1 46%). Gastritis activity in the antrum and corpus did not differ between the three groups. However, lymphocytic infiltration of the gastric antral mucosa was more pronounced in DU patients than in those with GORD or FD. CONCLUSIONS: H. pylori strains obtained from patients with mild to moderate erosive GORD show a virulence pattern similar to that found in DU patients. The presence of these virulence factors does not appear to protect against erosive lesions in the oesophagus.

Antigen stool test for assessment of Helicobacter pylori infection in patients with upper gastrointestinal bleeding.

BACKGROUND: Re-bleeding of Helicobacter pylori-associated peptic ulcer disease is reduced by H. pylori eradication. AIM: To validate a non-invasive test, the Premium Platinum HpSA stool test, in patients with upper gastrointestinal bleeding. METHODS: Stool samples of consecutive patients with relevant bleeding from gastric or duodenal ulcers or erosions were collected at initial endoscopy and during the following week. Samples were assessed using the HpSA test. H. pylori status was defined by three biopsy-based reference methods: culture, rapid urease test and histology. It was positive if culture was positive or if rapid urease test and histology were positive. RESULTS: One hundred and fourteen patients (mean age, 66 years) were included. In accordance with the definition, 56 (49%) were H. pylori positive. The sensitivity and specificity of the first stool sample were 84% and 90%, respectively. The respective values for two samples from consecutive days were 91% and 86%. In comparison with a serum immunoglobulin G antibody enzyme-linked immunoabsorbent assay, the HpSA test showed superior specificity. CONCLUSIONS: The diagnostic accuracy, in particular the sensitivity, of the HpSA stool test is reduced by upper gastrointestinal bleeding. The positive predictive value of 89%, however, justifies the initiation of eradication therapy on the basis of a positive stool test. A negative test result should be confirmed by a further diagnostic method.

[Epidemiology and pathogenesis of Helicobacter pylori infection]. / Epidemiologie und Pathogenese der Helicobacter pylori-Infektion.

Since Marshall and Warren reported the first isolation of Helicobacter pylori basic and clinical research on pathogenesis and epidemiology of Helicobacter pylori infection have been tremendous. Childhood is clearly established as the period of major risk for Helicobacter pylori acquisition. The transmission pathways may be several including the oral-oral, the gastro-oral or the fecal-oral transmission route. The colonization of Helicobacter pylori occurs exclusively in the gastric mucosa or in areas of gastric metaplasia especially in the duodenum. Helicobacter pylori possesses several factors to adhere to the epithelial cells and to cause mucosal damage. The acquisition of Helicobacter pylori always induces a chronic gastritis. The development to clinical manifestations (peptic ulcer or gastric cancer) are further dependent on specific bacterial strain virulence factors as well as on host and environment factors. The mechanisms involved in the inflammatory process have been elucidated in great detail and will further be focused and related to specific associated disease development.

High rate of post-therapeutic resistance after failure of macrolide-nitroimidazole triple therapy to cure Helicobacter pylori infection: impact of two second-line therapies in a randomized study.

BACKGROUND: The optimal second-line treatment after failed Helicobacter pylori therapy has not been established. AIMS: To ascertain whether quadruple therapy or triple therapy with omeprazole, clarithromycin and amoxicillin is the superior re-treatment after triple therapy containing a macrolide and a nitroimidazole, and to determine the impact of microbial in vitro resistance. METHODS: Patients after failed triple therapy were randomly allocated to one of two 1-week second-line treatments: omeprazole, 40 mg, clarithromycin, 500 mg, and amoxicillin, 1 g, all b.d.; or omeprazole, 20 mg b.d., bismuth subsalicylate, 600 mg q.d.s., metronidazole, 400 mg t.d.s., and tetracycline, 500 mg q.d.s. Post-therapeutic Helicobacter pylori status was assessed by 13C-urea breath test at least 4 weeks after treatment. RESULTS: The study was terminated after including 84 patients. H. pylori cure rates differed significantly: omeprazole-clarithromycin-amoxicillin: intention-to-treat, 43%; per protocol, 50%; omeprazole-bismuth subsalicylate-metronidazole-tetracycline: intention-to-treat, 68%; per protocol, 69%. The frequencies of resistance after first-line therapy were: metronidazole, 90%; clarithromycin, 71%; both combined, 68%. For clarithromycin resistance, H. pylori cure with omeprazole-clarithromycin-amoxicillin was 30% vs. 83% for clarithromycin susceptibility. CONCLUSIONS: Omeprazole-bismuth subsalicylate-metron- idazole-tetracycline was superior to omeprazole-clarithromycin-amoxicillin, but both therapies yielded unsatisfactory results. The high rate of post-therapeutic dual resistance has a negative impact on omepraz- ole-clarithromycin-amoxicillin, and probably also on omeprazole-bismuth subsalicylate-metronidazole-tetracycline, and limits the choice for second-line treatment.

Current standards in the diagnosis of Helicobacter pylori infection.

A large number of diagnostic tests are available for the diagnosis of Helicobacter pylori infection. These diagnostic methods include invasive and noninvasive methods. Culture yields the highest specificity and moreover allows the determination of strain resistance against antibiotics. Histology besides detection of H. pylori allows to assess morphological changes of the gastric mucosa. In clinical practice, the rapid urease test is very convenient and highly accurate. The (13)C-urea breath test and the recently developed stool antigen test are reliable noninvasive tests with a high diagnostic accuracy in pre- and posttreatment conditions. Serological tests have a lower diagnostic accuracy and should only be used for screening of H. pylori infection or after careful local validation.

Prevalence of Helicobacter pylori resistance to several antimicrobial agents in a region of Germany.

To evaluate the prevalence of resistance among Helicobacter pylori in Germany, the minimum inhibitory concentrations of amoxicillin, tetracycline, clarithromycin, and metronidazole were determined by means of the E test, for 271 Helicobacter pylori isolates cultured from biopsies taken during routine endoscopies in 1996 and 1997. The prevalence of metronidazole resistance was 32.1%, with resistance found more frequently in women (38.5%) than in men (24.4%). Clarithromycin resistance was rare (3.3%). Eight of nine strains resistant to clarithromycin were also resistant to metronidazole. Resistance to either metronidazole or clarithromycin was significantly (P=0.022) higher in patients with duodenal ulcer. No strain was found to be resistant to amoxicillin or tetracycline.