Furazolidone combination therapies for Helicobacter pylori infection in the United States

BACKGROUND: Antibiotic resistance has begun to impair the ability to cure Helicobacter pylori infection. AIM: To evaluate furazolidone as a component of combination therapies for treatment of H. pylori infection in the United States. METHODS: Patients with active H. pylori infection received furazolidone combination therapy for 14 days (furazolidone 100 mg and tetracycline 500 mg t.d.s.; omeprazole 20 mg o.d. in the morning and, depending on the pre-treatment antimicrobial susceptibility pattern, 500 mg of metronidazole or clarithromycin t.d.s.). RESULTS: A total of 27 patients received the metronidazole containing combination (cure rate 100%) and seven received the clarithromycin combination (cure rate 86%). Overall the cure rates for intention-to-treat was 97% (95% CI: 85% to 100%). The single failure took the clarithromycin containing combination for only 2 days (per protocol cure rate = 100%). Side-effects were common and led to discontinuation of therapy in 26% of patients. An attempt to eliminate metronidazole and clarithromycin and use furazolidone, tetracycline, and lansoprazole b.d. produced an unsatisfactory cure rate of 72%. CONCLUSION: Furazolidone combination therapy appears to be effective. Additional studies with different antimicrobial combinations and duration of therapy are warranted.     

Furazolidone-containing short-term triple therapies are effective in the treatment of Helicobacter pylori infection

BACKGROUND: A furazolidone-containing therapeutic regimen for Helicobacter pylori infection has attracted special interest in the face of a rising world-wide metronidazole resistant H. pylori, and the expense of currently used antimicrobial regimens. AIM: To evaluate the efficacy of furazolidone-containing regimens in eradicating H. pylori. METHODS: One-hundred and forty H. pylori positive patients with endoscopically confirmed duodenal ulcer or functional dyspepsia received one of four different regimens to eradicate H. pylori. In the first trial, the patients were randomly assigned to receive a 1-week course of furazolidone 100 mg b.d. and clarithromycin 250 mg b.d., with either tripotassium dicitrato bismuthate (TDB) 240 mg b.d. (FCB group) or lansoprazole 30 mg daily (FCL group). In the second trial, the patients were randomly assigned to receive a 1-week course of clarithromycin 250 mg b.d. and omeprazole 20 mg daily, with either furazolidone 100 mg b.d. (FCO group) or metronidazole 400 mg b.d. (MCO group). Endoscopy was repeated 4 weeks following completion of therapy with re-assessment of H. pylori status on gastric biopsies by histology and culture. RESULTS: Four patients (1 in FCB, 1 in FCO and 2 in MCO groups) dropped out because they refused a follow-up endoscopy. Eradication rates of H. pylori on an intention-to-treat basis in the FCB, FCL, FCO and MCO groups were 91% (32/35, 95% CI: 82-99%), 91% (32/35, CI: 82-99%), 86% (30/35, CI: 74-97%) and 74% (26/35, CI: 60-89%) (all P > 0.05), respectively. Mild side-effects occurred in 15% of the 140 patients. In MCO group, the eradication rate in the patients infected with metronidazole-sensitive isolates of H. pylori was 86%, but dropped to 67% in those with metronidazole-resistance strains (P = 0.198). CONCLUSION: One-week regimens containing furazolidone and clarithromycin in combination with TDB or a proton pump inhibitor fulfil the criteria for successful H. pylori therapy.     

One-week triple therapy with omeprazole, amoxycillin and either clarithromycin or metronidazole for cure of Helicobacter pylori infection

Aim: The present study was designed to evaluate the efficacy and tolerability of 1-week triple therapy regimens for Helicobacter pylori .
Methods: In two consecutive series, 120 patients with proven H. pylori infection and peptic ulcer disease or functional dyspepsia were treated with either omeprazole 20 mg b.d., amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. (OAC; n=60) or with omeprazole 20 mg b.d., amoxycillin 1 g b.d. and metronidazole 400 mg b.d. over 1 week (OAM; n=60). H. pylori infection was assessed by rapid urease test, culture and histology before and 4 weeks after cessation of the eradication therapy.
Results: H. pylori eradication succeeded in 53 out of 60 patients by omeprazole–amoxycillin–clarithromycin (OAC) (88%; 95% CI 77–95%) and in 47 out of 60 patients by omeprazole–amoxycillin–metronidazole (OAM) (78%; 95% CI 66–88%) (P=0.22). Nine patients of each group available for follow-up reported adverse events (15.0 and 15.5%, respectively) without necessity of discontinuation of the study medications. Serious adverse events were not observed.
Conclusions: Simple and convenient 1-week triple therapies consisting of omeprazole, amoxycillin and either clarithromycin or metronidazole are sufficiently effective in eradicating H. pylori infection.     

Comparison of two 3-day Helicobacter pylori eradication regimens with a standard 1-week regimen

BACKGROUND: The duration of Helicobacter pylori eradication regimens has decreased to 1 week with cure rates of over 90%. This can be attributed to the use of triple drug regimens including potent inhibitors of gastric acid secretion and clarithromycin. There is no theoretical reason why shorter regimens should not be possible. AIM: To compare two 3-day, low-dose, twice daily regimens with 1 week of omeprazole 20 mg b.d., clarithromycin 250 mg b.d., and metronidazole 400 mg b.d. (OCM) METHODS: Outpatients referred for gastroscopy were screened by biopsy urease test. H. pylori-positive patients were randomized to receive either lansoprazole 30 mg b.d., tri-potassium dicitrato bismuthate one tablet b.d., clarithromycin 250 mg b.d., and amoxycillin 1 g b.d. for 3 days (LTdbCA), or ranitidine bismuth citrate 400 mg b.d., clarithromycin 250 mg b.d. and amoxycillin 1 g b.d. for 3 days (RbcCA) or omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. for 1 week (OCM). They were not pre-treated with a gastric acid inhibitor. After 8 weeks, H. pylori status was assessed by 13C urea breath test. RESULTS: 974 out of 1114 patients referred for gastroscopy were screened by biopsy urease test. 140 patients were not screened either because they were anticoagulated or for technical reasons. 334 patients were H. pylori-positive: 154 were excluded mostly because of allergy to penicillin and personal reasons but 180 were randomized to treatment All regimens were well tolerated. For LTdbCA (n=60), RbcCA (n=59), and OCM (n=61) the H. pylori cure rates (95% CI) were 23% (12-34), 14% (5-23) and 87% (79-95), respectively, using intention-to-treat analysis and 25% (14-36), 15% (6-24) and 88% (80-96), respectively, if analysed per protocol. OCM was significantly superior to LTdbCA and RbcCA (P < 0.001) but there was no significant difference between regimens LTdbCA and RbcCA. CONCLUSIONS: OCM is an extremely effective H. pylori eradication regimen. The 3-day regimens tested both have poor cure rates. Pre-treatment with a proton pump inhibitor, higher doses or more frequent dosing may be necessary to increase the cure rate of short duration regimens. However, this could make them less acceptable than the H. pylori eradication regimens currently available.     

One-week triple vs. quadruple therapy for Helicobacter pylori infection - a randomized trial

BACKGROUND: Seven-day triple therapy including omeprazole, clarithromycin and amoxicillin has become the treatment of choice for Helicobacter pylori infection. However, 7 days of classical quadruple therapy combining omeprazole, tetracycline, metronidazole and bismuth may be an alternative to triple therapy. AIM: To compare triple vs. quadruple therapy for H.pylori eradication. METHODS: Three hundred and thirty-nine patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomized to receive omeprazole, 20 mg, amoxicillin, 1 g, and clarithromycin, 500 mg, all b.d., or omeprazole, 20 mg b.d., tetracycline chloride, 500 mg, metronidazole, 500 mg, and bismuth subcitrate, 120 mg, all t.d.s. Cure was defined as a negative urea breath test at least 2 months after treatment. RESULTS: Per protocol and intention-to-treat cure rates were 86%[95% confidence interval (CI), 80-91%] and 77% (95% CI, 70-83%) for triple therapy, and 89% (95% CI, 82-93%) and 83% (95% CI, 76-88%) for quadruple therapy. No significant differences between the groups were found in the cure rates, compliance or side-effects. CONCLUSION: One-week triple and quadruple therapy show similar results when used as first-line eradication treatment.     

High cure rate of Helicobacter pylori infection using tripotassium dicitrato bismuthate, furazolidone and clarithromycin triple therapy for 1 week

BACKGROUND: When metronidazole is used in bismuth-based or proton pump inhibitor-based triple therapy, the cure rate of Helicobacter pylori is usually high. However, metronidazole-resistant H. pylori strains, which are increasing in frequency, are a major cause of failed H. pylori eradication. AIM: To evaluate the efficacy of non-metronidazole containing bismuth-based triple therapy for H. pylori infection. METHODS: One-hundred and eighty H. pylori-positive patients with endoscopically documented peptic ulcer disease or functional dyspepsia were randomly assigned to one of three 1-week regimens containing tripotassium dicitrato bismuthate (also called colloidal bismuth subcitrate) 240 mg b.d. and two antibiotics: furazolidone 100 mg b.d. plus clarithromycin 250 mg b.d. (Group A); or clarithromycin 250 mg b.d. plus amoxycillin 1000 mg b.d. (Group B); or furazolidone 100 mg b.d. plus josamycin 1000 mg b.d. (Group C). H. pylori status was assessed by rapid urease test, histology and culture of gastric biopsy specimens taken from both the antrum and corpus, both before and at least 4 weeks after completion of therapy. RESULTS: Thirteen patients dropped out (3 in group A, 5 in group B and 5 in group C). Based on an intention-to-treat analysis, the eradication rates achieved in groups A, B and C were 88% (53/60), 58% (35/60) and 77% (46/60), respectively. These differences were significant between groups A and B (P < 0.001), as well as between groups B and C (P < 0.05). Side-effects occurred in 7 (12%) patients in group A, 3 (5%) in group B and 8 (13%) in group C, and were mild, with the exception of vomiting in one patient (group C) that resulted in withdrawal from the study. CONCLUSION: One-week triple therapy, consisting of tripotassium dicitrato bismuthate, low-dose furazolidone and low-dose clarithromycin, achieves a high cure rate of H. pylori.     

Low-dose lansoprazole and clarithromycin plus metronidazole vs. full-dose lansoprazole and clarithromycin plus amoxicillin for eradication of Helicobacter pylori infection

AIM: To compare, in a randomized controlled trial, the efficacy and tolerability of two 1-week triple therapies for Helicobacter pylori eradication. METHODS: One hundred and thirty-four consecutive patients with non-ulcer dyspepsia and H. pylori infection were randomized to receive lansoprazole 30 mg once daily, clarithromycin 250 mg twice daily, and metronidazole 500 mg twice daily (LCM group), or lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily (LCA group). H. pylori status was assessed by rapid urease test, histology and 13C-urea breath test before and after therapy. RESULTS: At 3 months, H. pylori eradication (intention- to-treat/per protocol analysis) was 92.4%/93.8% in the LCM group and 83.1%/85.7% in the LCA group (P=N.S.). Side-effects were more frequently reported in the LCA group (37.9%) than in the LCM group (19.7%) (P < 0.05). CONCLUSIONS: In this open, randomized controlled trial, eradication of H. pylori by low-dose lansoprazole and clarithromycin plus metronidazole was higher with significantly less side-effects than by full-dose lansoprazole and clarithromycin plus amoxicillin. This finding may be related to the stronger synergism of clarithromycin plus metronidazole, even at lower doses, than of clarithromycin plus amoxicillin. Considering the lower cost as well, LCM should be preferred to LCA in the eradication of H. pylori.     

One-week regimens containing ranitidine bismuth citrate, furazolidone and either amoxicillin or tetracycline effectively eradicate Helicobacter pylori: a multicentre, randomized, double-blind study

BACKGROUND: The metronidazole resistance of Helicobacter pylori strains has increased rapidly. AIM: To evaluate the efficacy and safety of new 1-week regimens containing ranitidine bismuth citrate, furazolidone and either amoxicillin or tetracycline. METHODS: One hundred and twenty patients with H. pylori-positive inactive duodenal ulcer or non-ulcer dyspepsia diagnosed by endoscopy were recruited randomly to receive one of two regimens for 7 days: ranitidine bismuth citrate, 350 mg b.d., furazolidone, 100 mg b.d., and either amoxicillin, 1000 mg b.d. (n=60), or tetracycline, 500 mg b.d. (n=60). H. pylori infection was identified by rapid urease testing and histology. 13C-Urea breath test was performed to evaluate the cure of H. pylori infection at least 4 weeks after completion of triple therapy. RESULTS: The eradication rates of H. pylori by ranitidine bismuth citrate-furazolidone-amoxicillin and ranitidine bismuth citrate-furazolidone-tetracycline regimens were 82% and 85% (P > 0.05), respectively, by intention-to-treat analysis, and 85% and 91% (P > 0.05), respectively, by per protocol analysis. Adverse effects were mild in both ranitidine bismuth citrate-furazolidone-amoxicillin and ranitidine bismuth citrate-furazolidone-tetracycline groups. CONCLUSIONS: One-week regimens containing ranitidine bismuth citrate, furazolidone and amoxicillin or tetracycline are well tolerated and effective for the eradication of H. pylori.     

Lansoprazole, clarithromycin and metronidazole for seven days in Helicobacter pylori infection

Background : This study determines the efficacy and safety of a 1-week triple therapy regimen of lansoprazole, clarithromycin and metronidazole in an area with a high prevalence of pre-treatment metronidazole-resistant strains of Helicobacter pylori .
Methods : Seventy-five H. pylori positive patients with gastritis or duodenal ulcer were entered into an open study of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. H. pylori status was determined by CLOtest, histology, culture and by ¹³C-urea breath test (repeated 28 days after treatment).
Results : Seventy-one patients completed the treatment and returned for follow-up. H. pylori was eradicated in 61 of 71 (86%) patients by per-protocol analysis, and in 61 of 75 (81%) patients by intention-to-treat analysis. H. pylori was eradicated in 12 of 16 (75%) patients with metronidazole-resistant strains compared with 22 of 24 (92%) in patients with metronidazole-sensitive strains of H. pylori ( P = 0.14). Forty-five patients reported at least one adverse event, and three patients stopped treatment due to them (two with headaches and one with diarrhoea).
Conclusions : A 1-week course of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. eradicates H. pylori in up to 86% of patients. It is of proven benefit in patients with pre-treatment metronidazole-resistant strains of H. pylori .     

Lansoprazole, levofloxacin and amoxicillin triple therapy vs. quadruple therapy as second-line treatment of resistant Helicobacter pylori infection

AIM: To test the efficacy of levofloxacin-based second-line therapy for resistant Helicobacter pylori infection. METHODS: One hundred and six patients who failed H. pylori eradication were randomized to receive (i) lansoprazole 30 mg, amoxicillin 1 g, levofloxacin 500 mg, all given twice daily for 7 days (LAL); or (ii) lansoprazole 30 mg twice daily, metronidazole 400 mg thrice daily, bismuth subcitrate 120 mg and tetracycline 500 mg four times daily for 7 days (quadruple). Post-treatment H. pylori status was determined by (13)C-urea breath test. RESULTS: Intention-to-treat and per-protocol H. pylori eradication rates were 57/60% for the LAL group and 71/76% for the quadruple group respectively. Metronidazole, clarithromycin, amoxicillin and levofloxacin resistance were found in 76%, 71%, 0% and 18% of patients, respectively. Levofloxacin resistance led to treatment failure in the LAL group. For patients with dual resistance to metronidazole and clarithromycin, the eradication rates were 79% in the LAL group (levofloxacin-sensitive) and 65% in the quadruple group (P=0.34). CONCLUSION: Lansoprazole, amoxicillin plus levofloxacin second-line therapy is comparable with quadruple therapy in efficacy. Subjects, especially those with dual resistance to metronidazole and clarithromycin, may consider levofloxacin-based therapy for levofloxacin-sensitive strains.     

Failure of a 1-day high-dose quadruple therapy for cure of Helicobacter pylori infection

BACKGROUND: The optimal duration of treatment for eradication of Helicobacter pylori has still to be defined. A 1-day high-dose quadruple therapy with a combination of amoxycillin (or tetracycline), metronidazole, a bismuth salt and a proton pump inhibitor has led to eradication rates of 57-77%. In view of the high frequency of metronidazole-resistant strains of H. pylori in Europe, we hypothesized that by using clarithromycin in place of metronidazole and by increasing the dose of proton pump inhibitor, the efficacy of a 1-day high-dose quadruple therapy could be improved. METHODS: Patients were randomized to receive either amoxycillin 1000 mg b.d., clarithromycin 500 mg b.d. and lansoprazole 30 mg b.d. for 7 days, or amoxycillin 2000 mg q.d.s., clarithromycin 500 mg q.d.s., lansoprazole 30 mg t.d.s. and bismuth subcitrate 240 mg q.d.s. for 1 day. RESULTS: It was originally intended to include 100 patients. The first planned interim analysis performed after follow-up was completed for 30 patients revealed H. pylori eradication rates of 80% (12/15) in the 7-day triple therapy group and 20% (3/15) in the 1-day quadruple therapy group, the difference being highly significant (P = 0.003). Because the efficacy of the 1-day treatment was so low, the study was stopped for ethical reasons. Eleven patients who failed with the 1-day treatment were re-treated with the 7-day triple therapy: the eradication rate was 91% (10/11). CONCLUSIONS: One-day high-dose quadruple therapy with amoxycillin, clarithromycin, lansoprazole and bismuth subcitrate is dramatically less effective than the classic 7-day triple therapy with the same antibiotics.     

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori—a randomized, controlled trial

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.     

Prospective evaluation of the macrolide antibiotic dirithromycin for the treatment of Helicobacter pylori.

BACKGROUND: Macrolide antibiotics are active in vitro and in vivo against Helicobacter pylori. We assessed a newer macrolide, dirithromycin, for the treatment of H. pylori in two separate studies. METHODS: Volunteers with H. pylori infection (by 13C-urea breath test) were randomly assigned to 2-week treatment regimens. Study 1: dirithromycin 500 mg q.d.s., dirithromycin 500 mg q.d.s. plus omeprazole 40 mg q.d.s., or dirithromycin 500 mg q.d.s. plus metronidazole 500 mg t.d.s. Study 2: dirithromycin 500 mg q.d.s. plus omeprazole 20 mg b.d., dirithromycin 1000 mg q.d.s. plus omeprazole 20 mg b.d., or amoxycillin 500 mg q.d.s. plus omepirazole 20 mg b.d. Four weeks after the completion of therapy a repeat 13C-urea breath test was done to assess for cure. RESULTS: No patient taking dirithromycin alone (n = 6) or in combination with omeprazole (n = 26) achieved cure of their infection. Eradication of H. pylori was seen in one of seven patients taking dirithromycin plus metronidazole. Five of 10 patients taking omeprazole-amoxycillin dual therapy had their H. pylori infection cured (P = 0.0007 vs. patients taking dirithromycin plus omeprazole). Eleven (47%) of 32 patients taking dirithromycin alone or combined with omeprazole reported side-effects, but only two (6%) stopped therapy prematurely as a result of side-effects. CONCLUSION: No subject taking dirithromycin alone or in combination with omeprazole had their H. pylori infection cured. Dirithromycin, in the regimen used, shows little promise in the treatment of patients with H. pylori infection.     

Metronidazole, omeprazole and clarithromycin: an effective combination therapy for Helicobacter pylori infection

Background: Successful treatment of Helicobacter pylori infection results in cure of peptic ulcer disease. Multidrug regimens are needed to cure this infection. We studied the effectiveness and side effect profile of two antibiotics active against Helicobacter pylori, metronidazole and clarithromycin, combined with omeprazole. Methods: We evaluated a combination therapy for H. pylori infection consisting of metronidazole (500 mg b.d.), omeprazole (20 mg b.d.), and clarithromycin (250 mg b.d.) for 2 weeks, followed by ranitidine 300 mg daily for 4 weeks. Results: Thirty-three patients with documented H. pylori infection were studied. Twenty had previously failed antimicrobial therapy, including one with metronidazole-based triple therapy and eight with macrolide-based therapy (five with clarithromycinbased therapy), and 11 with amoxycillin, tetracycline, and bismuth. H. pylori status was determined by histopathology using the Genta stain and by culture. H. pylori status was determined at entry and 4 weeks after completing antimicrobial therapy. The H. pylori infection was cured in 88% (95% CI = 72%–96%) including 90% of those who had failed previous anti-H. pylori therapies. Mild side effects were reported by 18%. Conclusion: We conclude that the combination of metronidazole, omeprazole and clarithromycin is an effective treatment for H. pylori infection.     

One-week low-dose triple therapy for Helicobacter pylori is sufficient for relief from symptoms and healing of duodenal ulcers

Aim : To test the hypothesis that 1-week low-dose triple therapy for H. pylori is sufficient for relief from dyspeptic symptoms and healing of duodenal ulcers.
Methods : Fifty-nine out-patients with duodenal ulcers and positive rapid urease test participated in this randomized, double-blind, two-centre study. All patients were treated for 1 week with omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. In a double-blind fashion, patients were then randomly treated for another 3 weeks with either omeprazole 20 mg once daily or an identical-looking placebo. Patients were investigated endoscopically before treatment for H. pylori , after 2 weeks and after 4 weeks. H. pylori infection was assessed by a ¹³C-urea breath test at the time of enrolment and 4 weeks after cessation of any study medication.
Results : Fifty-two patients were included in the 'all patients treated' analysis of efficacy. The overall H. pylori cure rate was 96% (95% CI=87–100%), with no difference between the treatment groups. After 2 weeks duodenal ulcer healing was confirmed in 91% (95% CI=80–100%) of patients treated with omeprazole and in 76% (95% CI=60–91%) in the placebo group ( P =0.14). After 4 weeks all ulcers had healed. Relief from dyspeptic symptoms and adverse events (13.8 and 16.7%) did not differ between the treatment groups.
Conclusions : One-week low-dose triple therapy consisting of omeprazole, clarithromycin and metronidazole is a highly effective and well-tolerated approach to the cure of H. pylori infection in patients with a duodenal ulcer. Our data suggest that continuation of antisecretory drug therapy beyond anti- H. pylori therapy is actually excessive regarding relief from dyspeptic symptoms and healing of duodenal ulcers.     

Effect of ornidazole and clarithromycin resistance on eradication of Helicobacter pylori in peptic ulcer disease

BACKGROUND: Clarithromycin and nitroimidazoles such as metronidazole and ornidazole are among the most frequently used antibiotics for curing Helicobacter pylori infection. However, controversial data exist on whether their in vitro resistance has a negative impact on treatment outcome. METHODS: Patients with H. pylori positive active peptic ulcer disease were randomly assigned to receive lansoprazole 30 mg o.d., amoxycillin 1 g b.d. and ornidazole 500 mg b.d. (LAO) or lansoprazole 30 mg o.d., amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC) for 2 weeks. Pre-treatment resistance to ornidazole and clarithromycin was assessed by Epsilometer (E-) test. Four weeks after completion of treatment, patients underwent a 13C urea breath test to assess H. pylori status. RESULTS: Data from 80 patients with active peptic ulcer disease and positive H. pylori status were analysed. The prevalence of primary drug resistance was 25% for metronidazole and 7.5% for clarithromycin. In patients treated with LAO, effective treatment was achieved in 87% of metronidazole-susceptible, but only 30% of metronidazole-resistant strains (P < 0.01). In the LAC group, therapy was successful in 81% of clarithromycin-susceptible strains, whereas treatment failed in all patients with primary clarithromycin resistance (n = 3). CONCLUSION: Resistance against nitroimidazoles significantly affects treatment outcome in H. pylori eradication therapy.     

The impact of antibiotic resistance on the efficacy of three 7-day regimens against Helicobacter pylori

BACKGROUND: Antibiotic resistance affects the success of anti-Helicobacter pylori therapies and varies greatly from country to country. AIM: To compare the efficacy of three short-term triple regimens in relation to H. pylori primary resistance in our region. METHODS: We enrolled 210 H. pylori-positive dyspeptic patients for this randomized, open, parallel-group study. Three arms of 70 patients each received the following 1-week regimens: (1) ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d. (RCM); (2) bismuth subcitrate 240 mg b.d. + amoxycillin 1000 mg b.d. + metronidazole 500 mg b.d. (BAM); (3) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d. + metronidazole 500 mg b.d. (OCM). H. pylori was assessed by CLO-test and histology before and 4 weeks after therapy. Antibiotic resistance was assessed by E-test. RESULTS: On intention-to-treat analysis RCM was more effective than OCM (84% vs. 69%; P < 0.03) and BAM (84% vs. 63%; P < 0.004). MIC determination was successful in 117 out of 210 patients (55%); metronidazole resistance was present in 52 out of 117 patients (44%) and clarithromycin resistance was present in 17 out of 117 patients (14%). Excellent cure rates were achieved when strains were sensitive to both antibiotics (100% with RCM and BAM and 90% with OCM), whereas RCM was superior to OCM (P=0.009) and BAM (P=0.001) with respect to overall resistant strains (94% vs. 57% and 38%, respectively). CONCLUSIONS: One-week RCM is the best regimen to eradicate H. pylori in our geographical area. This seems to be linked to the better ability of RCM compared to OCM and BAM in overcoming the high prevalence of H. pylori resistance to both metronidazole and clarithromycin in our region.     

First-line eradication therapy for Helicobacter pylori in primary health care based on antibiotic resistance: results of three eradication regimens

AIM: To determine the efficacy of three Helicobacter pylori eradication regimens and factors affecting the eradication results in Finland. METHODS: A total of 342 H. pylori-positive adult patients from primary health care referred for gastroscopy at 23 centres in different parts of Finland were randomized to receive either (i) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and metronidazole 400 mg t.d.s. (LAM), (ii) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC), or (iii) ranitidine bismuth citrate 400 mg b.d., metronidazole 400 mg t.d.s. and tetracycline 500 mg q.d.s. (RMT). A (13)C-urea breath test was performed 4 weeks after therapy. RESULTS: The eradication result could be assessed in 329 cases. Intention-to-treat cure rates of LAM, LAC, and RMT were 78, 91 and 81%. The difference was significant between LAM and LAC (P = 0.01) and between LAC and RMT (P = 0.04). The eradication rates in cases with metronidazole-susceptible vs. -resistant isolates were for LAM 93% vs. 53% (P = 0.00001), for LAC 95% vs. 84%, and for RMT 91% vs. 67% (P = 0.002). Previous antibiotic use, smoking, and coffee drinking reduced the efficacy of therapy. CONCLUSIONS: In unselected patients in primary health care, LAC was the most effective first-line eradication.     

Metronidazole containing quadruple therapy for infection with metronidazole resistant Helicobacter pylori: a prospective study

BACKGROUND: Metronidazole remains a key component of H. pylori infection therapy. It has been suggested that despite resistance, metronidazole may be effective when given at high dose with bismuth, tetracycline, and a proton pump inhibitor (quadruple therapy). AIM: To prospectively evaluate metronidazole quadruple therapy for treatment of metronidazole resistant H. pylori infection in the United States. METHODS: Patients infected with metronidazole resistant H. pylori were prospectively prescribed 14 days of quadruple therapy consisting of metronidazole 500 mg t.d.s., tetracycline 500 mg q.d.s., two bismuth subsalicylate tablets q.d.s., and omeprazole 20 mg o.d. RESULTS: A total of 26 patients were entered into the study; 22 for their first treatment and four as re-treatment for failed therapy. Of the 26 patients, 24 were cured (cure rate 92%; 95% CI: 78-99%). Both treatment failures reported full compliance to 14 days of therapy. Side-effects were common and resulted in premature discontinuation of therapy in 31%. Premature discontinuation did not reduce the cure rate. CONCLUSION: Quadruple metronidazole combination therapy is effective despite the presence of metronidazole resistance and should be considered as either first line therapy or for failures of twice-a-day combination therapies.