Jc Thijs

The influence of in vitro, nitroimidazole resistance on the efficacy of nitroimidazole-containing anti-Helicobacter pylori regimens : A meta-analysis

OBJECTIVES:The aim of this study was to determine the influence of nitroimidazole resistance (NIR) on the efficacy of treatment for Helicobacter pylori (H. pylori) infections by meta-analysis of the world literature.METHODS:A MEDLINE search, a manual search of all major gastroenterological journals from 1993 to 1997, and abstracts of gastroenterological and H. pylori meetings from 1993 to 1997 were performed. All treatment studies using a nitroimidazole and providing data about the medication used, dose frequency, total daily dose, duration of treatment, and eradication results in relation to NIR were included. Eradication had to be assessed by two biopsy-based tests or a urea breath test ≥4 wk after treatment. Individual studies were pooled into groups according to the medication used and the duration of treatment. The pooled estimate of the odds ratio (OR) of NIR for treatment failure and its 95% confidence interval (95% CI) were calculated for each group using the logit method. To detect any possible bias, funnel plots (plots of effect estimates against sample size) were constructed.RESULTS:A total of 91 treatment arms, including a total of 4823 patients, were evaluated. The pooled ORs of NIR for treatment failure (95% CI) of protonpump inhibitors, bismuth, and quadruple regimens were 5.2 (3.8–7.1), 5.9 (4.1–8.3), and 7.0 (3.1–16.0), respectively. Eradication rates were 90% in susceptible strains but <75% in resistant strains. In susceptible strains, neither treatment duration nor the choice of the second antibiotic influenced efficacy. In resistant strains, tetracycline was more effective than amoxicillin (bismuth regimens), and the longer the duration of regimens (bismuth-amoxicillin regimens) the more effective they were. Only quadruple regimens given for ≥1 wk were effective in resistant strains.CONCLUSIONS:NIR decreases treatment efficacy. Treatment duration and choice of other drugs influence the impact of NIR on treatment efficacy. If NIR is present, a nitroimidazole-containing regimen should be avoided or a quadruple regimen should be given for >1 wk.

Effect of Helicobacter pylori eradication on chronic gastritis during omeprazole therapy.

BACKGROUND We have previously observed that profound acid suppressive therapy inHelicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis. AIM To investigate ifH pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes. PATIENTS/METHODS In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months. RESULTS In the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in theH pylori positive group that becameH pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p⩽0.0001). The decrease in active and chronic inflammation in the corpus differed significantly compared with the persistentlyH pylori positive group (both p=0.001). For atrophy scores, no significant differences were observed betweenH pylori eradicated and persistentlyH pylori positive patients within one year of follow up. No changes were observed in the H pylori negative control group (n=26). CONCLUSIONS H pylori eradication prevents the increase in corpus gastritis associated with profound acid suppressive therapy. Longer follow up is needed to determine if H pylori eradication prevents the development of atrophic gastritis.

Efficacy and Side Effects of a Triple Drug Regimen for the Eradication of Helicobacter pylori

One hundred consecutive patients with Helicobacter pylori infection, as proven by culture, were treated with 120 mg colloidal bismuth subcitrate (CBS) four times daily, 250 mg tetracycline four times daily, and 250 mg metronidazole four times daily during 15 days. The patients were amply instructed in how to take the medicine and strongly urged to complete the prescribed course. In 66 of the 100 patients pretreatment metronidazole susceptibility was determined. Endoscopy was performed 3 months after cessation of treatment to check for H. pylori eradication by culture, urease testing, and histology. Side effects of the treatment were registered and classified into five groups on the basis of severity. Eradication was achieved in 93 of 100 patients (93%), in 61 of 62 patients with a metronidazole-sensitive strain (98.4%), and in 2 of 4 patients with a metronidazole-resistant strain (50%). Eighty-two per cent of the patients experienced no or just minor side effects; 15% had moderate side effects, and just 3% had severe side effects. Non-ulcer dyspepsia patients reported significantly more side effects than patients with peptic ulcer disease. With proper patient instruction, this treatment regimen is well tolerated and very effective for the eradication of metronidazole-sensitive H. pylori strains.

Prevalence of primaryHelicobacter pylori resistance to metronidazole and clarithromycin in The Netherlands

The minimum inhibitory concentrations of metronidazole and clarithromycin were determined for 780Helicobacter pylori strains collected in 1994 and 1995 from three different regions in The Netherlands. The overall prevalence of primary metronidazole resistance was 17%, with resistance found more frequently in women (24%) than in men (13%). There was no significant difference between the levels of resistance in the three regions. Primary clarithromycin resistance was rare (1%) and relatively infrequent as compared to that found in other countries. Four of the six strains resistant to clarithromycin were also resistant to metronidazole.

The influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate triple therapy regimens for Helicobacter pylori infection

: To assess the influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate‐based triple therapy regimens in two consecutive studies.

In vitro studies on stability and development of metronidazole resistance in Helicobacter pylori.

Seventy isolates of Helicobacter pylori from antral biopsy samples were tested for their susceptibilities to metronidazole by agar dilution. Seven (10%) of these clinical isolates appeared to be resistant to metronidazole. Sixty-three strains were susceptible. In 42 (67%) of the 63 susceptible isolates, resistant isolates were obtained by serial passage on plates containing subinhibitory concentrations of metronidazole. In 10 of these 42 strains, the acquired resistance appeared to be unstable. The difference between the stability of resistance that occurred after one or two passages and the stability of resistance that occurred after three passages was statistically significant (P < 0.006). Primary resistance in clinical isolates was a stable phenomenon. Whether the resistance that emerges during therapy in patients is stable or unstable needs to be established.

One-week triple therapy with omeprazole, amoxycillin and tinidazole for Helicobacter pylori infection: the significance of imidazole resistance

Background: Triple therapy involving a proton pump inhibitor and two antibiotics has been suggested as an effective treatment for Helicobacter pylori infection. The impact of imidazole resistance on the efficacy of such regimens is largely unknown.

Low cure rate of Helicobacter pylori infection with omeprazole and furazolidone dual therapy for one week

Furazolidone is an inexpensive antibiotic that has considerable anti‐Helicobacter pylori activity in vitro.

Short report: clarithromycin, an alternative to metronidazole in the triple therapy of Helicobacter pylori infection

Background: Triple therapy for Helicobacter pylori using metronidazole is less effective in patients with a metronidazole resistant strain. Moreover, metronidazole is responsible for many side‐effects. This open study examined the efficacy and side‐effects of a triple treatment regimen substituting clarithromycin for metronidazole.

The accuracy of the Helicobacter pylori stool antigen test in diagnosing H-pylori in treated and untreated patients

Objective and design To evaluate the performance of the Helicobacter pylori stool antigen test (HpSA test) in detecting H. pylori infection and monitoring the effect of treatment. This was done in two separate studies using either a biopsy or the 13C-urea breath test based ‘gold standard’ (in untreated and treated patients, respectively). Setting Endoscopy units of two general hospitals. Patients One hundred and twenty-eight dyspeptic patients undergoing endoscopy in the first study. Sixty-five patients receiving anti-H. pylori treatment in the second study. Results Sensitivity and specificity in untreated patients were 96.3% and 81.8%, respectively. Seven days after treatment, these figures were 20% and 95%, and 4 weeks after treatment they were 40% and 95%. Conclusion The HpSA test is accurate in untreated patients but fails in monitoring treatment success.