Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice.
(17/1291)
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)
The optimal antibiotic combination in a 5-day Helicobacter pylori eradication regimen.
(18/1291)
BACKGROUND: Current guidelines for Helicobacter pylori eradication recommend 7 days of a proton-pump inhibitor, clarithromycin (C), and either metronidazole (M) or amoxycillin (A). A shorter course would be cheaper and could be as effective. AIM: This study was designed to investigate the efficacy of three 5-day regimens based on lansoprazole (L). METHODS: 168 dyspepsia patients with H. pylori infection were randomized to receive a 5-day course of either LCM, LAC or CALM, and a 13C-urea breath test was performed after 4 weeks to assess eradication. RESULTS: 160 patients completed the study. Intention-to-treat eradication rates were as follows: LCM 81%, LAC 59%, CALM 88%. LCM and CALM gave significantly better eradication rates than LAC. There was no significant difference in adverse events across the three groups. Logistical regression analysis showed that the specific regimen used and the age of the patient were the only factors influencing eradication outcome. CONCLUSIONS: Five days of CALM yields acceptable eradication rates, and is cheaper than conventional 7-day proton pump inhibitor-triple therapy. It appears to offer good results in metronidazole-resistant strains of H. pylori. A randomized trial comparing 5-day CALM with conventional 7-day therapy is needed before this regimen can be recommended for routine use. (+info)
Synergistic in vitro antimalarial activity of omeprazole and quinine.
(19/1291)
Previous studies have shown that the proton pump inhibitor omeprazole has antimalarial activity in vitro. The interactions of omeprazole with commonly used antimalarial drugs were assessed in vitro. Omeprazole and quinine combinations were synergistic; however, chloroquine and omeprazole combinations were antagonistic. Artemisinin drugs had additive antimalarial activities with omeprazole. (+info)
Randomized controlled comparison of nitroimidazoles for the eradication of Helicobacter pylori and relief of ulcer-associated and non-ulcer dyspepsia.
(20/1291)
BACKGROUND: A combination of omeprazole, clarithromycin and either metronidazole or tinidazole is commonly used for Helicobacter pylori eradication. Metronidazole is considerably cheaper than tinidazole but the two have not previously been compared in a randomized trial. METHODS: One hundred and twenty dyspeptic H. pylori-positive patients with endoscopically defined peptic ulcer [DU (n = 65), GU (n = 12)] or non-ulcer dyspepsia (NUD, n = 43) were randomized to receive a 1-week course of twice daily omeprazole 20 mg, clarithromycin 250 mg and either metronidazole 400 mg (OCM) or tinidazole 500 mg (OCT) in a double-blind fashion. Eradication of H. pylori, safety and side-effects of treatment, dyspeptic symptom score and consumption of antisecretory drugs were assessed at 6 weeks and 1 year after treatment. RESULTS: H. pylori eradication was successfully achieved in 57/60 (95%, ITT analysis) of patients receiving OCT and 58/60 (97%, ITT analysis) receiving OCM. Both regimens had similar side-effect profiles, which accounted for only one patient withdrawal. All patients remained uninfected (as assessed by 14C-urea breath test) at 1-year follow-up, but major symptom improvements and decreased antisecretory drug use were only seen in patients with DU (P<0.0001). CONCLUSIONS: Treatment with OCM is as effective as the more expensive OCT at eradicating H. pylori. H. pylori eradication results in long-term relief of dyspeptic symptoms and reduced antisecretory consumption only in patients with DU, and not in those with NUD. (+info)
Head-to-head comparison of 1-week triple regimens combining ranitidine or omeprazole with two antibiotics to eradicate Helicobacter pylori.
(21/1291)
BACKGROUND: Triple therapies containing omeprazole and ranitidine have been shown to be equivalent in eradicating H. pylori infection, but have been assessed either separately or head-to-head, only in small trials. AIM: To carry out a large randomized controlled study comparing omeprazole and ranitidine combined with two antibiotic combinations for 1 week. METHODS: Three hundred and twenty H. pylori-positive patients were randomly subdivided into four equal-sized groups and received one of the following treatments: OAM = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; RAM = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + metronidazole 500 mg b.d.; OAC = omeprazole 20 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s.; RAC = ranitidine 300 mg b.d. + amoxycillin 1 g b.d. + clarithromycin 250 mg t.d.s. The assessment of H. pylori status was performed before and 4 weeks after the end of therapy by means of CLO-test and histology. H. pylori infection was considered to be eradicated when both tests were negative. RESULTS: OAM and RAM eradicated H. pylori in 89% and 85% of cases on per protocol (P = 0.48) and in 77% and 75% of cases on intention-to-treat analyses (P = 0.71). OAC and RAC eradicated H. pylori in 67% and 70% of cases on per protocol (P = 0.68) and in 57% and 64% of cases on intention-to-treat analyses (P = 0.41). In contrast, there was significant difference between OAM and OAC (P<0.01) and between RAM and RAC (P<0.05). Side-effects occurred in 15%, 10%, 17% and 16% of patients with respect to the above four subgroups. CONCLUSIONS: Omeprazole and ranitidine combined with two antibiotics for 1 week are equally effective in the eradication of H. pylori infection, and these results question the role of profound acid suppression in the eradication of the bacterium. (+info)
The effect of antibiotic resistance on the outcome of three 1-week triple therapies against Helicobacter pylori.
(22/1291)
BACKGROUND: Resistance of Helicobacter pylori to antibiotics may be a major reason for treatment failure. AIM: To evaluate the effect of primary H. pylori resistance to antibiotics on the cure rates of three anti-H. pylori 1-week triple therapies. METHODS: One hundred and sixteen consecutive patients diagnosed H. pylori-positive by gastric histology, rapid urease test and culture were enrolled. Activity of tested antibiotics was determined by means of the E-test. Patients were treated for 7 days with: (i) pantoprazole 40 mg o.d. plus amoxycillin 1 g b.d. and metronidazole 250 mg q.d.s. (PAM); (ii) pantoprazole 40 mg o.d. plus clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s. (PCM); or (iii) pantoprazole 40 mg o.d. plus amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (PAC). Two months after completion of therapy, endoscopy and gastric biopsies were repeated. RESULTS: Primary resistance rates to metronidazole, clarithromycin and amoxycillin were 17.2, 6.9 and 0%, respectively. Overall H. pylori cure rates expressed as intention-to-treat and per protocol analyses were, respectively, 79% and 86% with PAM, 82% and 89% with PCM, and 85% and 85% with PAC. Significantly lower cure rates were observed in metronidazole-resistant patients treated with PAM (56% vs. 96%, P = 0.01) or PCM (50% vs. 97%, P = 0.01). A trend towards lower H. pylori cure rates was observed in clarithromycin-resistant patients treated with PCM (67% vs. 91%, P = 0.74) or PAC (50% vs. 87%, P = 0.68). CONCLUSION: Primary resistance to metronidazole influences the H. pylori cure rate of anti-H. pylori proton pump inhibitor-based triple therapies which include this antibiotic. A similar trend exists for primary clarithromycin resistance. (+info)
Bedtime ranitidine does not eliminate the need for a second daily dose of omeprazole to suppress nocturnal gastric pH.
(23/1291)
BACKGROUND: We have previously shown that 70% of patients experience nocturnal gastric acid breakthrough (defined as pH<4 for more than 60 min between 22.00 and 06.00 hours) on twice a day (b.d.) proton pump inhibitor. Adding 150 or 300 mg of ranitidine at bedtime is more effective than additional omeprazole at bedtime in control of night-time acid breakthrough. AIM: To assess whether omeprazole 20 mg AM plus ranitidine 150 mg HS would be as effective as omeprazole 20 mg before breakfast and dinner (b.d. AC) in intragastric pH control, particularly during the overnight period. METHODS: Twenty healthy volunteers (11 males, 9 females, mean age 32.7 years) were treated with omeprazole (OME) 20 mg b.d. AC and placebo HS or omeprazole 20 mg AM and placebo before dinner plus ranitidine (RAN) 150 mg HS for 7 days, in a randomized, double-blind, crossover design, with a 1 week washout between study periods. On day 8 subjects were monitored for 24 h with a single channel pH probe placed in the stomach 10 cm below the proximal border of the LES. Percentage time pH<4 for total, upright and recumbent positions were compared between the two regimens using Wilcoxon matched pairs testing. RESULTS: Expressed in median values of percentage time pH<4: upright time intragastric pH<4 on OME 20 mg b.d. AC was 18.9 compared to 29.7 on OME AM + RAN HS (P = 0.003). Recumbent time pH<4 on OME 20 mg b.d. AC was 23.45 compared to 44.75 on OME AM + RAN HS (P = 0.02). CONCLUSION: Bedtime ranitidine does not eliminate the need for an evening dose of omeprazole to control intragastric pH in patients requiring more than a single daily dose of omeprazole. (+info)
Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism.
(24/1291)
AIMS: To examine the effect of ticlopidine administration on the activities CYP2C19 and CYP3 A in vivo using omeprazole as a model substrate. METHODS: A single dose of 40 mg omeprazole was administered orally with or without ticlopidine (300 mg daily for 6 days) to six Japanese extensive metabolisers with respect to CYP2C19. Blood samples were taken for the measurement of plasma concentrations of omeprazole, 5-hydroxyomeprazole and omeprazole sulphone. RESULTS: Ticlopidine administration increased omeprazole Cmax (1978+/-859/ 3442+/-569 (control phase/ticlopidine phase, nm )) and decreased the oral clearance of omeprazole (CL/F; 25.70+/-16. 17/10.76+/-1.16 (control phase/ticlopidine phase, l h-1 )) significantly. The 5-hydroxyomeprazole to omeprazole AUC ratio (0. 817+/-0.448/0.236+/-0.053 (control phase/ticlopidine phase)) and the 5-hydroxyomeprazole to omeprazole sulphone AUC ratio (1.114+/-0. 782/0.256+/-0.051 (control phase/ticlopidine phase)) were decreased significantly after ticlopidine administration. The decrease in omeprazole CL/F and the 5-hydroxyomeprazole to omeprazole AUC ratio correlated significantly with their respective absolute values when the drug was given alone. The decrease in CL/F following ticlopidine administration correlated with that in the 5-hydroxyomeprazole to omeprazole AUC ratio. CONCLUSIONS: These findings suggest that ticlopidine inhibited the in vivo activity of CYP2C19, but not, or to a lesser extent CYP3 A4, and that the magnitude of inhibition by ticlopidine is related to the in vivo activity of CYP2C19 before inhibition. (+info)