Aa van Zwet

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.

Alterations in Penicillin-Binding Protein 1A Confer Resistance to β-Lactam Antibiotics in Helicobacter pylori

ABSTRACT Most Helicobacter pylori strains are susceptible to amoxicillin, an important component of combination therapies for H. pylori eradication. The isolation and initial characterization of the first reported stable amoxicillin-resistant clinical H. pylori isolate (the Hardenberg strain) have been published previously, but the underlying resistance mechanism was not described. Here we present evidence that the β-lactam resistance of the Hardenberg strain results from a single amino acid substitution in HP0597, a penicillin-binding protein 1A (PBP1A) homolog of Escherichia coli. Replacement of the wild-type HP0597 (pbp1A) gene of the amoxicillin-sensitive (Amxs) H. pylori strain 1061 by the Hardenberg pbp1A gene resulted in a 100-fold increase in the MIC of amoxicillin. Sequence analysis of pbp1A of the Hardenberg strain, the AmxsH. pylori strain 1061, and four amoxicillin-resistant (Amxr) 1061 transformants revealed a few amino acid substitutions, of which only a single Ser414→Arg substitution was involved in amoxicillin resistance. Although we cannot exclude that mutations in other genes are required for high-level amoxicillin resistance of the Hardenberg strain, this amino acid substitution in PBP1A resulted in an increased MIC of amoxicillin that was almost identical to that for the original Hardenberg strain.

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.

Explanations for high rates of eradication with triple therapy using metronidazole in patients harboring metronidazole-resistant Helicobacter pylori strains.

In 4 of 17 Helicobacter pylori strains obtained from antral biopsy samples, the registered primary resistance (MIC, > 32 microgram/ml) appeared to be nonstable after prolonged microaerophilic incubation. In all resistant strains tested, susceptibility could be obtained when culture under normal microaerophilic conditions was preceded by a period of anaerobic incubation. Both of these findings may explain the observed discrepancy between the results of in vitro susceptibility tests and the eradication obtained in vivo.

One-Week Triple Therapy With Ranitidine Bismuth Citrate, Clarithromycin and Metronidazole Versus Two-Week Dual Therapy With Ranitidine Bismuth Citrate and Clarithromycin for Helicobacter pylori Infection: A Randomized, Clinical Trial

Objective:The aim of this study was to compare the efficacy and side effects of 1-wk triple therapy with ranitidine bismuth citrate (RBC) 400 mg b.i.d., clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d., to 2-wk dual therapy with RBC 400 mg b.i.d. and clarithromycin 500 mg b.i.d. for H. pylori infection in a randomized, clinical trial.Methods:Patients (18–80 yr) with a culture proven H. pylori infection were randomized to one of these regimens. Side effects were scored on a semiquantitative scale. Endoscopy was performed ≥4 wk after treatment. Antral biopsy samples were taken for hematoxylin-eosin stain (HE), rapid urease test, and culture and corpus samples for culture and HE. Two weeks after the endoscopy, a 13C-urea breath test was performed. Eradication failure was defined as detection of H. pylori by culture or by at least two other tests.Results:A total of 104 patients, 54 men, age 54 ± 14 yr, (36 duodenal ulcer, 16 gastric ulcer, and 52 functional dyspepsia) were included. Gender, age, and diagnosis were comparable in both groups. Fourteen of 52 patients in both triple and dual therapy, respectively, had significant side effects, but all patients completed the course. Eradication results were 49 of 52 (94%; 95% CI: 84–99%) and 50 of 52 (96%; 95% CI: 87–100%) on intention to treat analysis and 44 of 46 (96%; 95% CI: 85–99%) and 48 of 49 (98%; 95% CI: 89–100%) on per protocol analysis for triple and dual therapy respectively.Conclusion:Both regimens are very effective and well tolerated in the treatment of H. pylori infection. The triple regimen has the advantage of being shorter.

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.

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.