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Notes: Aim : To compare the efficacy of different regimens in patients in whom previous Helicobacter pylori eradication therapy has failed.Methods : In this study named StratHegy patients (n = 287) were randomized to receive one of three empirical triple therapy regimens or a strategy based on antibiotic susceptibility. The empirical regimens were omeprazole, 20 mg b.d., plus amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d., for 7 days (OAC7), clarithromycin, 500 mg b.d., for 14 days (OAC14) or metronidazole, 500 mg b.d., for 14 days (OAM14). In the susceptibility-based strategy, patients with clarithromycin-susceptible strains received OAC14, whilst the others received OAM14. The 13C-urea breath test was performed before randomization and 4–5 weeks after eradication therapy.Results : In the intention-to-treat analysis, the eradication rates for empirical therapies were as follows: OAC7, 47.4% (27/57); OAC14, 34.5% (20/58); OAM14, 63.2% (36/57); it was 74.3% (84/113) for the susceptibility-based treatment (P 〈 0.01 when compared with OAC7 and OAC14). In patients receiving clarithromycin, the eradication rates were 80% for clarithromycin-susceptible strains and 16% for clarithromycin-resistant strains; in patients receiving OAM14, the eradication rates were 81% for metronidazole-susceptible strains and 59% for metronidazole-resistant strains.Conclusions : Eradication rates of approximately 75% can be achieved with second-line triple therapy based on antibiotic susceptibility testing. If susceptibility testing is not available, OAM14 is an appropriate alternative.

Notes: Aim : To study risk factors for failure of Helicobacter pylori eradication treatment.Methods : Individual data from 2751 patients included in 11 multicentre clinical trials carried out in France and using a triple therapy, were gathered in a unique database. The 27 treatment regimens were regrouped into four categories.Results : The global failure rate was 25.8%[95% CI: 24–27]. There was a difference in failure rate between duodenal ulcer patients and non-ulcer dyspeptic patients, 21.9% and 33.7%, respectively (P 〈 10−6). In a random-effect model, the risk factors identified for eradication failure in duodenal ulcer patients (n = 1400) were: to be a smoker, and to have received the group 4 treatment, while to receive a 10 day treatment vs. 7 days protected from failure. In non-ulcer dyspeptic patients (n = 913), the group 2 treatment was associated with failure. In both groups, age over 60 was associated with successful H. pylori eradication. There were less strains resistant to clarithromycin in duodenal ulcer patients than in non-ulcer dyspeptic patients. Clarithromycin resistance predicted failure almost perfectly.Conclusion : Duodenal ulcer and non-ulcer dyspeptic patients should be managed differently in medical practice and considered independently in eradication trials.

Notes: The occurrence of refractory Helicobacter pylori infection is increasing. When the bacteria are not eradicated it means that the antibiotics have not reached the gastric mucosa at a sufficient concentration and over a sufficient time lapse to kill them. The main reasons for this are poor patient compliance, resistant bacteria, low gastric pH and a high bacterial load. Therefore, when administering a new treatment, it is important to choose antibiotics which do not face resistance problems and which increase the dosage of antisecretory drugs and the duration of treatment and, if possible, to add a topical agent such as bismuth salt.The recommended empirical strategy is to prescribe quadruple therapy or, alternatively, 2-week triple therapy including amoxicillin–metronidazole, tetracycline–metronidazole or amoxicillin–rifabutin. However, when H. pylori is susceptible, clarithromycin can still be used. In the case of a high level of metronidazole resistance, furazolidone can be employed. In each case, it is important to ensure good patient compliance, and counselling is helpful in this regard. However, the best approach remains the prevention of refractory H. pylori infection and, for this purpose, antimicrobial susceptibility testing before first-line therapy is important and should be encouraged.

Notes: Helicobacter pylori eradication rates in France after therapy with omeprazole, amoxicillin and clarithromycin are among the lowest in Europe. This study evaluated alternative eradication regimens.〈section xml:id="abs1-2"〉〈title type="main"〉Methods: Helicobacter pylori-positive patients (n=323) with non-ulcer dyspepsia were randomized to receive one of four 1-week regimens consisting of omeprazole, 20 mg b.d., plus either: amoxicillin, 1000 mg b.d., and clarithromycin, 500 mg b.d. (OAC); bacampicillin, 1200 mg b.d., and clarithromycin, 500 mg b.d. (OBC); clarithromycin, 250 mg b.d., and metronidazole, 500 mg b.d. (OCM); or amoxicillin, 1000 mg b.d, and azithromycin, 500 mg on day 1 and 250 mg on days 2–5 (OAAz). Eradication was confirmed by urea breath test 4–6 weeks after treatment. Susceptibility testing was performed in the case of eradication failure.〈section xml:id="abs1-3"〉〈title type="main"〉Results:The eradication rate with OAAz was 38% (95% CI, 25.6–49.4) on intention-to-treat analysis, which was lower (P 〈 0.05) than with the other regimens [OCM, 61% (50.0–72.8); OBC, 65% (54.0–76.5); OAC, 72% (61.8–81.8)]. Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:OAC remains the reference treatment for H. pylori eradication in France, although bacampicillin offers a useful alternative to amoxicillin. Susceptibility testing should be considered after unsuccessful eradication therapy.

Notes: Whilst the role of Helicobacter pylori eradication in managing duodenal ulcers has been established, consensus regarding the ideal regimen has not been achieved.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Patients with H. pylori-positive active duodenal ulcer were randomly assigned to receive triple therapy with amoxycillin 1000 mg b.d. + clarithromycin 500 mg b.d. + omeprazole 20 mg daily for 10 days (ACT-10) or dual therapy with clarithromycin 500 mg t.d.s. + omeprazole 40 mg daily for 14 days (Dual). No additional acid suppression was provided following eradication therapy. Endoscopy, with biopsy for culture and histology, as well as 13C-urea breath testing (13C-UBT) were performed pre-treatment to assess H. pylori infection. H. pylori eradication was established at 4–6 weeks follow-up with culture (2 antral, 1 corpus biopsies), histology (2 antral biopsies), and 13C-UBT. Ulcer healing by endoscopy and change in clinical symptoms were also assessed at 4–6 weeks.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Two hundred and sixty-seven (267) patients were randomized to ACT-10 (n=137) or Dual therapy (n=130). By per-protocol and intention-to-treat analyses, H. pylori eradication at 4–6 weeks follow-up was 91% (115/127) and 88% (120/136), respectively, for ACT-10 patients and 59% (68/115) and 55% (72/130), respectively, for Dual therapy patients (P〈0.001 for both analyses). Ulcer healing was high in both treatment groups: ACT-10, 93% (118/127) and 90% (122/136), respectively; and Dual therapy, 91% (104/114) and 85% (111/130), respectively. Pre-treatment resistance to clarithromycin was low (4%, 8/214) as compared to metronidazole resistance which was over 40%. Emergence of resistance to clarithromycin was observed in 2% of patients receiving ACT-10 and in 25% of those receiving Dual therapy. ACT-10 and Dual therapy patients experienced similar rates of drug-related adverse events (33% vs. 32%, respectively) and discontinuation from therapy due to an adverse event (1.5% vs. 5%, respectively). More than 90% of patients were compliant with each prescribed medication.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusion:In patients with active duodenal ulcer, a 10-day course of amoxycillin–clarithromycin-based triple therapy without additional acid suppression is highly effective in eradicating H. pylori and healing duodenal ulcer.

Notes: Aim : Non-invasive tests for the assessment of Helicobacter pylori status are now an integral part of the management strategies for patients with dyspepsia. The aim of this study was to evaluate a urine based antibody ELISA and a near patient urine test for the diagnosis of H. pylori infection in a European population.Methods : Urine samples were collected from 449 patients (240 females, 209 males, mean age 54 years), with dyspeptic symptoms but no previous H. pylori eradication therapy, at five centres in four European countries. All patients underwent GI endoscopy and biopsies were taken for H. pylori diagnosis. Urine samples were analysed using an IgG ELISA (URINELISA) and a near patient urine test (RAPIRUN). In addition, a serum IgG ELISA (Pyloriset-EIA-GIII), a whole blood test (Pyloriset-Screen) and a 13C-urea breath test were performed.Results : The sensitivity of the urine based ELISA and the near patient urine test was 90% and 82%, and the specificity 68% and 83%, respectively. The accuracy of the serum ELISA and the whole blood test was comparable with the urine based test.Conclusion : The urine based ELISA and the near patient urine test are just as accurate as the serological tests. This comparable accuracy and complete non-invasiveness of the former gives it an advantage over blood based tests. This limits the application of these tests in general practice.

Notes: Besides the well established Helicobacter pylori reservoir, i.e. the human stomach, numerous other sources have been hypothesized. However, none has been definitely proven. In some instances (pig, sheep), Helicobacter species closely related but different from H. pylori were detected but the results were misleading because culture of sufficiently discriminating molecular techniques were not used. In other cases, the strain was really H. pylori (cat) but the case was anecdotal or the animal species (monkey) has so little contact with humans that the possible source has no epidemiological consequence. This is also the case for houseflies which theoretically can be a vehicle, but practically speaking are not because of too few viable bacteria present in faeces. Molecular epidemiology studies demonstrating the route of transmission (faecal–oral, oral–oral or gastro–oral) are still lacking but recent studies have confirmed the presence of viable H. pylori in vomitus and in faeces in the event of diarrhoea.

Notes: Significant progress and new insights have been gained in the 4 years since the first Maastricht Consensus Report, necessitating an update of the original guidelines. To achieve this, the European Helicobacter Pylori Study Group organized a meeting of specialists and experts from around the world, representatives from National Gastroenterology Societies and general practitioners from Europe to establish updated guidelines on the current management of Helicobacter pylori infection. The meeting took place on 21–22 September 2000.A ‘test and treat’ approach is recommended in adult patients under the age of 45 years (the age cut-off may vary locally) presenting in primary care with persistent dyspepsia, having excluded those with predominantly gastro-oesophageal reflux disease symptoms, non-steroidal anti-inflammatory drug users and those with alarm symptoms. Diagnosis of infection should be by urea breath test or stool antigen test.As in the previous guidelines, the eradication of H. pylori is strongly recommended in all patients with peptic ulcer, including those with complications, in those with low-grade gastric mucosa-associated lymphoid tissue lymphoma, in those with atrophic gastritis and following gastric cancer resection. It is also strongly recommended in patients who are first-degree relatives of gastric cancer patients and according to patients’ wishes after full consultation.It is advised that H. pylori eradication is considered to be an appropriate option in infected patients with functional dyspepsia, as it leads to long-term symptom improvement in a subset of patients. There was consensus that the eradication of H. pylori is not associated with the development of gastro-oesophageal reflux disease in most cases, and does not exacerbate existing gastro-oesophageal reflux disease. It was agreed that the eradication of H. pylori prior to the use of non-steroidal anti-inflammatory drugs reduces the incidence of peptic ulcer, but does not enhance the healing of gastric or duodenal ulcer in patients receiving antisecretory therapy who continue to take non-steroidal anti-inflammatory drugs.Treatment should be thought of as a package which considers first- and second-line eradication therapies together. First-line therapy should be with triple therapy using a proton pump inhibitor or ranitidine bismuth citrate, combined with clarithromycin and amoxicillin or metronidazole. Second-line therapy should use quadruple therapy with a proton pump inhibitor, bismuth, metronidazole and tetracycline. Where bismuth is not available, second-line therapy should be with proton pump inhibitor-based triple therapy. If second-line quadruple therapy fails in primary care, patients should be referred to a specialist. Subsequent failures should be handled on a case-by-case basis by the specialist. In patients with uncomplicated duodenal ulcer, eradication therapy does not need to be followed by further antisecretory treatment. Successful eradica- tion should always be confirmed by urea breath test or an endoscopy-based test if endoscopy is clinically indicated. Stool antigen test is the alternative if urea breath test is not available.

Notes: Resistance of Helicobacter pylori to antibiotics included in current regimens used to eradicate H. pylori is a major reason for failure. The definition of resistance is not simple, and the clinical relevance of in vitro results must be considered. The different methods of testing antibiotics cannot apply in all cases.Resistance to clarithromycin has a low prevalence rate (〈10%) and its mechanism is well defined (point mutation on the 23S rRNA genes, and decreased binding of the antibiotics to the ribosome). Its clinical relevance is not questioned and, because of a clear occurrence of a bimodal strain population, the method for detecting resistance is not crucial.Resistance to nitroimidazoles is much more common, probably in the range of 30% or more in Europe. Neither the mechanism of action of metronidazole resistance nor its mechanism of is well known. The redox potential inside the cell which is important in reducing metronidazole to its active metabolite is probably a key element, but the exact metabolites involved are not yet known. Metronidazole resistance was found to be clinically relevant when standard triple therapy was used. The relevance is questioned for triple therapies including a proton pump inhibitor, clarithromycin and metronidazole. More clinical data are needed in this field and the use of agar dilutions is recommended to assess the susceptibility of H. pylori to metronidazole.The mechanism of resistance to quinolones has been described but these compounds are not currently used for H. pylori infection. No resistance has yet been described for amoxycillin but continuous surveillance is needed in order to detect new cases, as was recently the case for tetracycline resistance.