Susceptibility of multidrug-resistant strains of Mycobacterium tuberculosis to amoxycillin in combination with clavulanic acid and ethambutol. (1/1164)

Thirty clinical isolates of Mycobacterium tuberculosis, 20 of which were multidrug-resistant (MDR), were tested for susceptibility to different combinations of amoxycillin, clavulanic acid and subinhibitory concentrations of ethambutol. beta-Lactamase production was assessed semiquantitatively with the nitrocefin method and susceptibility testing was performed with the BACTEC method. All isolates were beta-lactamase positive and were resistant to 16 mg/L amoxycillin. The MIC of amoxycillin in combination with clavulanic acid was > or =2 mg/L for 27/30 (90%) isolates. Addition of subinhibitory concentrations of ethambutol significantly reduced the MIC of amoxycillin for all tested isolates. Twenty-nine (97%) isolates had an MIC of amoxycillin of < or =0.5 mg/L when subinhibitory concentrations of ethambutol were added; this is well below the concentrations achievable in serum and tissue.  (+info)

Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months' follow up. The Optimal Regimen Cures Helicobacter Induced Dyspepsia (ORCHID) Study Group. (2/1164)

OBJECTIVES: To determine whether eradication of Helicobacter pylori relieves the symptoms of functional dyspepsia. DESIGN: Multicentre randomised double blind placebo controlled trial. SUBJECTS: 278 patients infected with H pylori who had functional dyspepsia. SETTING: Predominantly secondary care centres in Australia, New Zealand, and Europe. INTERVENTION: Patients randomised to receive omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily or placebo for 7 days. Patients were followed up for 12 months. MAIN OUTCOME MEASURES: Symptom status (assessed by diary cards) and presence of H pylori (assessed by gastric biopsies and 13C-urea breath testing using urea labelled with carbon-13). RESULTS: H pylori was eradicated in 113 patients (85%) in the treatment group and 6 patients (4%) in the placebo group. At 12 months follow up there was no significant difference between the proportion of patients treated successfully by intention to treat in the eradication arm (24%, 95% confidence interval 17% to 32%) and the proportion of patients treated successfully by intention to treat in the placebo group (22%, 15% to 30%). Changes in symptom scores and quality of life did not significantly differ between the treatment and placebo groups. When the groups were combined, there was a significant association between treatment success and chronic gastritis score at 12 months; 41/127 (32%) patients with no or mild gastritis were successfully treated compared with 21/123 (17%) patients with persistent gastritis (P=0. 008). CONCLUSION: No convincing evidence was found that eradication of H pylori relieves the symptoms of functional dyspepsia 12 months after treatment.  (+info)

The DU-MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy. (3/1164)

AIM: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6-month treatment-free period in patients with active duodenal ulcer. METHODS: This was a double-blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1-week b. d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C-urea breath test and histology, performed at pre-entry, at 4 weeks after the end of all therapy and at 6 months. RESULTS: The intention-to-treat (intention-to-treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention-to-treat/per protocol): OMC-85% and 92%, OAC-78% and 87% and O-0% (O). Ulcer healing (intention-to-treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high. CONCLUSION: The OMC and OAC 1-week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.  (+info)

The influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate triple therapy regimens for Helicobacter pylori infection. (4/1164)

AIM: To assess the influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate-based triple therapy regimens in two consecutive studies. METHODS: In the first study, patients with a culture-proven Helicobacter pylori infection were treated with ranitidine bismuth citrate 400 mg, metronidazole 500 mg, and clarithromycin 500 mg, all twice daily for 1 week (RMC). In the second study, amoxycillin 1000 mg was substituted for clarithromycin (RMA). Susceptibility testing for metronidazole was performed with the E-test. Follow-up endoscopy was performed after >/= 4 weeks. Antral biopsy samples were taken for histology and urease test, and culture and corpus samples for histology and culture. RESULTS: 112 patients, 53 males, age 55 +/- 14 years (39 duodenal ulcer, 7 gastric ulcer and 66 gastritis) were treated with RMC, and 89 patients, 52 males, age 58 +/- 15 years (23 duodenal ulcer, 7 gastric ulcer and 59 gastritis) were treated with RMA. For RMC, intention-to-treat eradication results were 98% (59/60, 95% CI: 91-100%) and 95% (20/21, 95% CI: 76-100%) for metronidazole susceptible and resistant strains, respectively (P = 0.45). For RMA these figures were 87% (53/61, 95% CI: 76-94%) for metronidazole susceptible strains and 22% (2/9, 95% CI: 3-60%) for resistant strains (P = 0.0001). CONCLUSION: Both regimens are effective in metronidazole susceptible strains. However, in contrast to the amoxycillin-containing regimen, that containing clarithromycin is also effective in resistant strains.  (+info)

Ampicillin-sulbactam and amoxicillin-clavulanate susceptibility testing of Escherichia coli isolates with different beta-lactam resistance phenotypes. (5/1164)

The activities of ampicillin-sulbactam and amoxicillin-clavulanate were studied with 100 selected clinical Escherichia coli isolates with different beta-lactam susceptibility phenotypes by standard agar dilution and disk diffusion techniques and with a commercial microdilution system (PASCO). A fixed ratio (2:1) and a fixed concentration (clavulanate, 2 and 4 micrograms/ml; sulbactam, 8 micrograms/ml) were used in the agar dilution technique. The resistance frequencies for amoxicillin-clavulanate with different techniques were as follows: fixed ratio agar dilution, 12%; fixed concentration 4-micrograms/ml agar dilution, 17%; fixed ratio microdilution, 9%; and disk diffusion, 9%. Marked discrepancies were found when these results were compared with those obtained with ampicillin-sulbactam (26 to 52% resistance), showing that susceptibility to amoxicillin-clavulanic acid cannot be predicted by testing the isolate against ampicillin-sulbactam. Interestingly, the discrimination between susceptible and intermediate isolates was better achieved with 4 micrograms of clavulanate per ml than with the fixed ratio. In contrast, amoxicillin susceptibility was not sufficiently restored when 2 micrograms of clavulanate per ml was used, particularly in moderate (mean beta-lactamase activity, 50.8 mU/mg of protein) and high-level (215 mU/mg) TEM-1 beta-lactamase producer isolates. Four micrograms of clavulanate per milliliter could be a reasonable alternative to the 2:1 fixed ratio, because most high-level beta-lactamase-hyperproducing isolates would be categorized as nonsusceptible, and low- and moderate-level beta-lactamase-producing isolates would be categorized as nonresistant. This approach cannot be applied to sulbactam, either with the fixed 2:1 ratio or with the 8-micrograms/ml fixed concentration, because many low-level beta-lactamase-producing isolates would be classified in the resistant category. These findings call for a review of breakpoints for beta-lactam-beta-lactamase inhibitors combinations.  (+info)

Effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease. (6/1164)

BACKGROUND: Duodenal ulcer disease is strongly associated with Helicobacter pylori infection of the gastric mucosa. Eradication of H pylori from the gastric mucosa in adults is associated with long term healing of ulcers. AIMS: To follow a cohort of children with duodenal ulcer disease for a minimum of two years after the eradication of H pylori. PATIENTS AND METHODS: Over a three year period, all children diagnosed with duodenal ulcer disease had their symptoms documented and their H pylori status evaluated. The histories of these children were carefully screened to determine previous symptoms and to document previous treatment regimens. RESULTS: Sixteen children were diagnosed with ulcers and 15 were available for treatment and long term follow up. The median age at which symptoms first occurred was 10.5 years (range, 6-14) and the median duration of symptoms was 24 months (range, 2-60). Ten of the children had been treated with H2 receptor antagonists for a median of 3.5 months (range, 1-60). Duodenal ulcers healed in all children after eradication of H pylori and all children have remained asymptomatic for a median of 37 months (range, 26-62). No child has required subsequent admission to hospital. CONCLUSION: Eradication of H pylori is very effective in the long term healing of duodenal ulcer disease. H pylori eradication should be the standard treatment for all infected children who present with duodenal ulcer disease.  (+info)

Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxycillin and clarithromycin increases the cure rate of Helicobacter pylori infection. (7/1164)

AIM: To evaluate the efficacy of polaprezinc, a mucosal protective agent, in combination with a 7-day triple therapy containing lansoprazole, amoxycillin and clarithromycin, as a treatment for Helicobacter pylori. METHODS: Sixty-six consecutive patients suffering from dyspeptic symptoms with H. pylori infection were randomly allocated to one of two regimens: one group (LAC; n = 31) received lansoprazole 30 mg b.d., amoxycillin 500 mg b.d. and clarithromycin 400 mg b.d. for 7 days. The other group (LACP; n = 35) received the LAC regimen plus polaprezinc 150 mg b.d. for 7 days. H. pylori status was evaluated by rapid urease test, histology and culture at entry and 4 weeks after treatment. RESULTS: Five patients did not complete the treatment: no follow-up endoscopy was performed on two patients in the LAC group; one patient in the LAC group and two in the LACP group had their treatment stopped due to severe diarrhoea. By per protocol analysis, H. pylori eradication was achieved in 24 of the 28 evaluable patients (86%; 95% CI: 72-100%) after LAC therapy, and in 33 of the 33 evaluable patients (100%) after LACP therapy (P < 0.05). On intention-to-treat analysis, the rates of eradication were 24 of 31 patients (77%; 95% CI: 62-93%) in the LAC group, and 33 of 35 patients (94%; 95% CI: 86-100%) in the LACP group (P < 0.05). CONCLUSION: A 7-day triple therapy with lansoprazole, amoxycillin and clarithromycin is effective in H. pylori eradication, but this regimen is significantly improved by the addition of polaprezinc.  (+info)

Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice. (8/1164)

BACKGROUND: The effectiveness of Helicobacter pylori eradication regimens has not been extensively investigated in the clinical practice setting. The optimal treatment choice after an initial failed eradication attempt has not been determined. AIMS: To evaluate proton pump inhibitor-based triple therapies as first-line eradication regimens in clinical practice, and to establish the efficacy of second-line regimens in the context of an initial failed eradication attempt. METHODS: Three hundred and eight patients with dyspepsia and evidence of H. pylori at endoscopy were recruited. As first-line therapy, 116 patients received omeprazole 20 mg b.d. in combination with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) while 192 patients received omeprazole 20 mg b.d. in combination with metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC). H. pylori status was reassessed at least 4 weeks after therapy (25 patients failed to attend for further testing). Of 52 patients with an initial failed eradication attempt, 20 patients received a 1 week quadruple therapy regimen incorporating omeprazole 20 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s., 20 patients received a 2-week proton pump inhibitor-based triple therapy regimen as described, and 12 patients received a further 1-week proton pump inhibitor-based triple therapy regimen. RESULTS: Including 308 patients, the intention-to-treat (ITT) eradication rates for OAC and OMC as first-line regimens were 72% (95% CI: 63-80%) and 73% (95% CI: 67-79%) respectively. A per protocol (PP) analysis on the 283 patients who completed follow-up gives an initial eradication rate of 78% (95% CI: 69-86%) for OAC and 79% (95% CI: 73-85%) for OMC. There were 60 patients (21%; 95% CI: 17-26%) in whom the initial eradication attempt was unsuccessful. With second-line therapy, H. pylori was successfully eradicated in a further 35/52 (67%; 95% CI: 58-73%) patients. The eradication rates with the quadruple regimen and 2-week triple therapy regimens were 75% (95% CI: 56-94%) and 80% (95% CI: 63-98%) respectively (P = 0. 71). The eradication rate with a repeat 1-week regimen was 33% (95% CI: 7-60%). CONCLUSIONS: The eradication rates achieved in this 'in practice' study with recommended first-line 1-week proton pump inhibitor-based triple therapy regimens were lower than the rates achieved with similar regimens in the clinical trial setting. A repeat 1-week proton pump inhibitor-based triple therapy regimen was not successful as a salvage therapy. Both the 2-week proton pump inhibitor-based triple therapy regimen and the 1-week quadruple therapy regimen were successful second-line treatments in >/=75% of patients.  (+info)

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