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.     

Omeprazole, bismuth and clarithromycin in the sequential treatment of Helicobacter pylori infection

Aims: To assess the therapeutic potential of clarithromycin, a new macrolide with high anti-Helicobacter pylori activity, given with bismuth salts and omeprazole in different regimens aimed at simplifying the treatment of H. piylon-related gastritis. Methods: Eighty-eight patients with proven H. pylori infection and gastritis were treated with one of the following four regimens: omeprazole 40 mg/day for one week (group A. n = 14); omeprazole 40 mg/day for one week followed by clarithromycin 1 g/day for 2 weeks (group B, n = 26); omeprazole 40 mg/day for one week followed by tripotassium dicitrato bismuthate 480 mg/day and clarithromycin 1 g/day, both for two weeks (group C, n = 26); and tripotassium dicitrato bismuthate 480 mg/day and clarithromycin 1 g/day for two weeks (group D, n = 22). Presence of H. pylori, histology and electron microscopy were assessed at entry and four weeks after the end of each treatment. Results: Omeprazole alone had no effect on H. pylori status. The highest eradication rate was obtained in group C patients (81%), a proportion significantly greater than that observed in group B (50%, P < 0.03) or group D patients (55%, P < 0.05). Conclusion: Sequential treatment may be a useful option in the treatment of H. pylori-related gastritis.     

Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or without clarithromycin

Background: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking. Methods: Patients with active duodenal ulcer and H. pylori were enrolled in a double-blind, randomized, placebo-controlled multi-centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured. Results: One-hundred and fifty-four patients were recruited and randomized to omeprazole plus clarithromycin (n= 74) or to omeprazole plus placebo (n= 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72–91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0–7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71–91%) and at 4 weeks in 100% (95% CI: 95–100%), compared with 77% (95% CI: 66–86%) and 97% (95% CI: 91–100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1–16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63–86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side-effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P= 0.304). Ninety per cent of patients took at least 90% of their prescribed medication. Conclusions: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12-month recurrence from 76% to 6%.     

Influence of clarithromycin dosage on pantoprazole combined triple therapy for eradication of Helicobacter pylori

Background:

Low-dose clarithromycin (250 mg b.d.) in combination with omeprazole and metronidazole has been recommended for the eradication of Helicobacter pylori. Whether the substitution of omeprazole by pantoprazole requires adjustment of the clarithromycin dose is not known.

Aim:

To directly compare the efficacy and tolerability of two different dosages of clarithromycin in combination with pantoprazole and metronidazole.

Methods:

One hundred and sixty-three patients with endoscopically confirmed gastritis, gastric or duodenal ulcers and positive H. pylori findings in the rapid urease test were randomized and treated for 7 days with pantoprazole (40 mg b.d.), metronidazole (500 mg b.d.) and clarithromycin using either a regimen of 500 mg b.d. (group PMC 500) or 250 mg b.d. (group PMC 250). Eradication success was determined no less than 4 weeks after concluding therapy using the ¹³C-urea breath test.

Results:

One-hundred and thirty-nine patients completed the study. Based on a per protocol analysis, successful eradication was documented in 63/70 patients (90.0%) in group PMC 500 and in 62/69 patients (89.9%) in group PMC 250. Based on the intention-to-treat analysis, eradication rates were 78.8% (group PMC 500) and 75.6% (group PMC 250). The incidence of adverse effects was significantly higher in patients receiving PMC 500 (50.0%) than in those receiving PMC 250 (25.4%).

Conclusions:

Triple therapy with pantoprazole, metronidazole and clarithromycin provides an efficient eradication regimen for H. pylori infection. A low dose of clarithromycin is equal to a higher dose in therapeutic efficacy and it offers the advantage of improved tolerance and lower cost.

     

Addition of metronidazole to omeprazole/amoxycillin dual therapy increases the rate of Helicobacter pylori eradication: a double-blind, randomized trial

Aims: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen. Methods: In this double-blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 60). H. pylori status was assessed by ¹³C-urea breath test at entry and at 4 weeks post-treatment. Results: H. pylori infection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P < 0.0001, 95% CI for the difference: + 30 to + 62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side-effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P < 0.05). Conclusions: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higher H. pylori eradication rate than omeprazole and amoxycillin alone, with acceptable tolerability.     

Pharmacoeconomic comparison of Helicobacter pylori eradication regimens

Background Helicobacter pylori is the most important etiologic agent for development of peptic ulcer, chronic gastritis and gastric carcinomas. It is now well established that H. pylori eradication treatment is more cost-effective than acid suppressing therapies alone for the treatment of peptic ulcer disease. However, the comparative cost-effectiveness of various H. pylori eradication regimens is still not clear.Objective This study was designed to make a pharmacoeconomic comparison of different H. pylori eradication regimens in patients with peptic ulcer disease or chronic gastritis, using real-world cost and effectiveness data.Setting Istanbul University Hospital and Marmara University Hospital.Method A total of 75 patients diagnosed as H. pylori (+) by endoscopy were randomized to receive one of the seven H. pylori treatment protocols. These protocols were as follows: (LAC) = ‘lansoprazole 30 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid’ for 7 days and (OCM) = ‘omeprazole 20 mg bid + clarithromycin 250 mg bid + metronidazole 500 mg bid’; (OAM) = ‘omeprazole 40 mg qd + amoxicillin 500 mg tid + metronidazole 500 mg tid’; (MARB) = ‘metronidazole 250 mg tid + amoxicillin 500 mg qid + ranitidine 300 mg hs + bismuth 300 mg qid’; (OAC) = omeprazole 20 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid’; (OCA) = omeprazole 40 mg bid + clarithromycin 500 mg bid + amoxicillin 1 g bid’; (OAB) = ‘omeprazole 20 mg bid + amoxicillin 500 mg tid + bismuth 300 mg qid’ each for 14 days. Only direct costs were included in the analysis. Effectiveness was measured in terms of “successful eradication”. The cost-effectiveness ratios of the regimens were calculated using these effectiveness and cost data. The perspective of the study was assumed as the Government’s perspective.Main outcome measure Cost-effectiveness ratios of eradication regimens.Results MARB and OCA regimens were found to be more cost-effective than the other treatment regimens. The eradication rates and cost-effectiveness ratios calculated for these protocols were 90% (€158.7) for MARB and 90% (€195.8) for OCA regimen.Conclusion This study confirms the importance of using local pharmacoeconomic data. Analyses such as this give decision-makers the tools to choose a better treatment option which is both highly effective yet and has a low cost.     

Rapid eradication of Helicobacter pylori infection

Background/aims: Current Helicobacter pylori eradication therapy for peptic ulcer disease usually involves a 2-week course of either a bismuth preparation or omeprazole in combination with antibiotics. We have studied a shorter, 7-day course of treatment to assess efficacy and tolerability. Methods: Four hundred and thirty-six patients, in three non-randomized groups, received omeprazole (40 mg mane), amoxycillin (500 mg t.d.s.) and metronidazole (400 mg t.d.s.): 308 patients received the triple combination for 14 days; 80 patients were treated for 7 days; and 48 patients received omeprazole and amoxycillin for 7 days but metronidazole for only 5 days. Results: Helicobacter pylori was eradicated in 89.5%, 91.1% and 87.5%, respectively (98.3%, 92.9% and 100% of metronidazole-sensitive isolates and 75.6% and 88.2% of metronidazole-resistant isolates in the first two groups). Side effects were significantly more frequent in patients who received 14 days (49%) compared with 7 days of treatment (33%); only 8/308 and 1/128 patients, respectively, failed to complete the course. Conclusions: On the basis of efficacy, tolerability and cost, we conclude that a 7-day course of the omeprazole (40 mg mane), amoxycillin (500 mg t.d.s.) plus metronidazole (400 mg t.d.s.) combination is effective therapy for the eradication of H. pylori.     

Omeprazole, azithromycin and either amoxycillin or metronidazole in eradication of Helicobacter pylori in duodenal ulcer patients

Background

Azithromycin is a new generation, acid stable, macrolide antibiotic that achieves remarkably high concentrations in gastric tissue (above the minimal inhibitory concentration for Helicobacter pylori) after oral administration.

Aim

To establish whether azithromycin plus omeprazole in association with either amoxycillin or metronidazole are useful in curing H. pylori infection in patients with a duodenal ulcer.

Methods

One hundred patients with active duodenal ulcers and H. pylori infection were treated with omeprazole (days 1–10, 40 mg b.d.; days 11–24, 40 mg o.m.; days 25–42, 20 mg o.m.) plus azithromycin 500 mg o.m. for the first 6 days. Patients were randomly assigned to receive either amoxycillin 1 g b.d. (OAzA group; n = 50) or metronidazole 400 mg t.d.s. (OAzM group; n = 50) during the first 10 days of treatment. H. pylori status was determined by urease test and histology before the treatment and 6 weeks after completion of therapy.

Results

Ninety-seven patients completed the study. H. pylori infection was eradicated in 85% (41/48) of patients in the OAzA group (intention-to-treat analysis 82%) vs. 74% (36/49) of patients in the OAzM group (intention-to-treat analysis: 72%) (N.S.). All ulcers had healed after 6 weeks of omeprazole treatment. Side-effects, usually minor, were recorded in 13% (OAzA group) and 47% (OAzM group) of patients (P < 0.001), but therapy was discontinued for only one patient in the OAzA group (N.S.).

Conclusion

Ten days of treatment with omeprazole plus (for the first 6 days) azithromycin and either amoxycillin or metronidazole provides effective regimens to cure H. pylori infection in patients with duodenal ulcer disease.

     

Metronidazole, ranitidine and clarithromycin combination for treatment of Helicobacter pylori infection (modified Bazzoli's triple therapy)

Background: Multi-drug regimens are generally required to reliably cure Helicobarter pylori infection. Metronidazole, clarithromycin and omeprazole has proven to be an effective combination therapy with a cure rate of 90% or greater. Methods: We evaluated a 14-day combination regimen for H. pylori infection consisting of metronidazole 500 mg b.d., clarithromycin 250 mg b.d. and ranitidine 300 mg b.d. (MRC) instead of omeprazole. Ranitidine alone was continued for an additional 4 weeks. H. pylori status was determined by rapid urease testing. histopathology using the Genta stain, and by culture at entry and 4 weeks after completing antimicrobial therapy. Results: Twenty-seven patients with documented peptic ulcer disease and H. pylori infection were treated. Five had previously failed macrolide-based antimicrobial therapy: none had received metronidazole. All ulcers were healed at week 6 except one patient taking naproxen; his H. pylori infection was cured. Overall, H. pylori infection was cured in 78% (95% CI = 58–91%). In patients with clarithromycin-sensitive isolates, the cure rate was 20 of 23 (87%, 95% C.I. = 66–97%); only one of four patients (25%) with clarithromycin-resistant isolates was cured. In contrast, four of five patients with metronidazole-resistant isolates were cured (80%). In patients with isolates sensitive to both antibiotics, the cure rate was 16 of 18 (89% 95% C.I. = 65–99%). Mild side effects were reported by 27%, including diarrhoea and altered taste. Compliance averaged 98%. Conclusion: These results suggest that the combination of metronidazole, ranitidine and clarithromycin results in high cure rates in patients with clarithromycin-sensitive isolates. Omeprazole may not be required for Bazzoli's triple therapy; and large multicentre comparative trials are indicated.     

A new 1-week therapy for Helicobacter pylori eradication: rani- tidine bismuth citrate plus two antibiotics

Background: One-week triple regimens are currently the most recommended therapy for the eradication of Helicobacter pylori. No previous study has evaluated the efficacy of a short-term regimen combining ranitidine bismuth citrate with two antibiotics. Methods: Seventy-two consecutive H. pylori-positive dyspeptic patients were recruited for this randomized, three-centre, open, parallel-group study. They were subdivided into two groups receiving either ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (group A) or ranitidine bismuth citrate 400 mg b.d. + clarithromycin 250 mg b.d. and metronidazole 250 mg q.d.s (group B) for 1 week. H. pylori infection was assessed by CLO-test and histology on both antral and corpus biopsies before and at least 4 weeks after the end of therapy. The bacterium was considered eradicated when both tests were negative. Eradication rates and the number of side-effects were evaluated in each group. The Chi-squared test was used for statistical analysis. Results: One patient with only CLO-test positivity was erroneously randomized to group B and four patients dropped out of the study (two in group A and two in group B), mainly because they refused the second endoscopy. In group A, H. pylori was eradicated in 31 of 36 patients intention-to-treat = 86%; 95% CI = 71–95% and (per protocol 31/34 = 91%; 95% CI = 76–98%). Side-effects occurred in 10 patients (27%) and they were generally mild. In group B, H. pylori was eradicated in 29 of 35 patients (intention-to-treat = 83%; 95% CI = 66–93%; and per protocol 29/33 = 88%; 95% CI = 72–97%). Seven patients (20%) complained of modest side-effects. There was no significant difference between the two treatment arms (P = N.S.); no severe adverse events occurred and none of the patients was withdrawn from the study because of them. Conclusions: The co-administration of ranitidine bismuth citrate plus clarithromycin at low dosage and metronidazole in twice daily doses for 1 week is a short, effective and well-tolerated regimen for the eradication of H. pylori. These findings should provide the impetus for large-scale investigations.     

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. Methods: 36 patients with a H. pylori infection, proven by culture, were treated with tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 250 mg q.d.s. and clarithromycin 250 mg q.d.s. for 10 days. Eradication was defined as a negative culture and histological examination of antral biopsy specimens, taken at least 6 weeks after completion of the treatment. Results: Eradication was achieved in 26 patients (72%). The treatment was well tolerated with only 4 (11 %) of the patients having significant side-effects. Conclusion: Triple therapy with clarithromycin seems to be less effective than standard triple treatment when the prevalence of metronidazole resistance is low. It is suggested, however, that this combination could be a valuable alternative in areas with a high prevalence of metronidazole resistance.     

Ranitidine bismuth citrate versus omeprazole triple therapy for the eradication of Helicobacter pylori and healing of duodenal ulcer

Aim:

To compare the efficacy and safety of triple therapy with omeprazole plus amoxycillin and clarithromycin vs. ranitidine bismuth citrate plus amoxycillin and clarithromycin in the treatment of Helicobacter pylori-associated duodenal ulcers.

Methods:

Eighty-one patients with duodenal ulcers were randomized to the following treatments: 39 cases with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week plus omeprazole 20 mg b.d. for 2 weeks (omeprazole + amoxycillin + clarithromycin (OAC)), and 42 cases to the same regimen of amoxycillin and clarithromycin for 7 days plus ranitidine bismuth citrate 400 mg b.d. for 2 weeks (ranitidine bismuth citrate + amoxycillin + clarithromycin (RbAC)). Upper gastrointestinal endoscopy was performed together with a rapid urease test and histological examination of antral and corpus biopsy samples prior to treatment and 4 weeks after the end of therapy.

Results:

Thirty-four patients in the OAC group and 38 in the RbAC group completed the treatment and 4-week follow-up. H. pylori was eradicated in 30 of 34 patients (88%) in the OAC group and in 32 of 38 patients (84%) in the RbAC group according to a per-protocol analysis (P = N.S.). Thirty-three (97%) patients treated with OAC and 36 (95%) treated with RbAC presented healed duodenal ulcers at 4 weeks (P = N.S.). On an intention-to-treat basis there was no difference in H. pylori eradication between the OAC (77%) and RbAC groups (76%); duodenal ulcer healing was achieved in 85 and 86% of patients in the OAC and RbAC groups, re- spectively (P = N.S.).

Conclusion:

The OAC and RbAC triple therapy regimens proved equally effective in both H. pylori eradication and in duodenal ulcer healing.

     

Eradication of Helicobacter pylori with lansoprazole and clarithromycin

Background: Helicobacter pylori eradication with omeprazole and clarithromycin varies between 40 and 80%. The dose, frequency and duration of treatment may account for these differences. Lansoprazole, a recently introduced proton pump inhibitor, is a more potent H. pylori bacteriostat in vitro than omeprazole. The aim of this open, comparative, randomized study was to investigate the efficacy and safety of lansoprazole 30 mg once or twice a day (and for 2 vs. 4 weeks) plus clarithromycin 500 mg t.d.s. for 2 weeks, in the eradication of H. pylori. Methods: Sixty-six patients with H. pylori infection received clarithromycin 500 mg t.d.s. for 2 weeks and one of four lansoprazole regimens: 30 mg once a day for 2 (Group 1, n= 16) or 4 (Group 2, n= 16) weeks, or 30 mg b.d. for 2 (Group 3, n= 18) or 4 (Group 4, n= 16) weeks. H. pylori eradication was determined by the ¹³C-urea breath test 4 weeks after finishing treatment. Results: Per protocol analysis (53 patients) shows that H. pylori was eradicated in 6/13 (46%) in Group 1, 7/13 (54%) in Group 2, 9/14 (64%) in Group 3 and 9/13 (69%) in Group 4. Thirty-one of 68 patients experienced side effects. Analysis on an intention-totreat basis gave similar results. Conclusion: The dose of lansoprazole appears to be more important than the duration of therapy. Dual therapy with lansoprazole and clarithromycin should be investigated further as a possible treatment regimen for H. pylori infection.     

A randomized prospective comparison of clarithromycin versus amoxycillin in combination with omeprazole for eradication of Helicobacter pylori

Aim: To compare H. pylori eradication rates using omeprazole in conjunction with either amoxycillin or clarithromycin. Background: Omeprazole with amoxycillin is the most widely used dual therapy regimen for eradication of H. pylori. A recent open study suggested a high eradication rate combining omeprazole with the newer macrolide, clarithromycin. Methods: A randomized prospective trial in 54 patients was conducted to compare 2 weeks of treatment with omeprazole 40 mg once daily and either amoxycillin 500 mg three times daily or clarithromycin 500 mg three times daily. H. pylori eradication was assessed using the ¹³C urea breath test. Results: Eradication was achieved in 18/26 (69.2%) of subjects treated with omeprazole and amoxycillin and 18/25 (72.0%) of those treated with omeprazole and clarithromycin (P= N.S.). Minor side effects, most commonly altered taste, were reported by 16% of patients and were more frequent in those randomized to clarithromycin (P= 0.01). Conclusions: These regimens are similarly effective. However, clarithromycin is more expensive, associated with a greater frequency of side effects and, unlike amoxycillin, resistance by H. pylori has been reported. This suggests that clarithromycin may be a useful alternative when there is penicillin allergy or previous treatment failure, but it should not replace amoxycillin as first choice in omeprazole-based dual therapy.     

Eradication of Helicobacter pylori with lansoprazole, roxithromycin and metronidazole—an open pilot study

Background:

The most extensively studied Helicobacter pylori eradication regimen comprises omeprazole, clarithromycin and metronidazole. Macrolide antibiotics other than clarithromycin should achieve similar efficacy, but they have not yet been thoroughly tested.

Aim:

To determine the efficacy and safety of a triple therapy regimen using lansoprazole, roxithromycin, and metronidazole on the basis of multicentre out-patient care in an open pilot study.

Methods:

163 patients with duodenal ulcer and proven H. pylori infection received lansoprazole 30 mg b.d., roxithromycin 300 mg b.d. and metronidazole 500 mg b.d. for 7 days followed by another 7 days of lansoprazole 30 mg once daily. H. pylori status was determined by urease quick test, histology, microbiology and ¹³C-urea breath test before starting and at least 4 weeks after completing treatment.

Results:

150 patients were available for evaluation; H. pylori was successfully eradicated in 84.7% (127/150) as determined by urease quick test, 78.0% (117/150) by histology, 81.3% (109/134) by ¹³C-urea breath test; and in 75.3% (113/150), at least two tests were negative. Side-effects were reported in 34 patients (most commonly diarrhoea and changes in liver function tests), in two cases the study medication was interrupted. Prior to treatment, 23% of the H. pylori isolates were resistant against metronidazole and 3.4% against roxithromycin. After unsuccessful treatment, 84% of the isolates were resistant against metronidazole and 21% against roxithromycin. Primary resistance to metronidazole increased the chance of treatment failure approximately sevenfold (7% vs. 53%).

Conclusions:

For H. pylori eradication, the combination of lansoprazole, roxithromycin and metronidazole proved to be as safe as other current triple therapy regimens, while a comparison of efficacy rates yet remains to be assessed in prospective controlled trials. The metronidazole-resistant H. pylori is not rare in Germany and, in the present study, has strongly influenced treatment success.

     

Comparison of omeprazole and lansoprazole in short-term triple therapy for Helicobacter pylori infection

Background:

Effective anti-Helicobacter pylori therapies with few side-effects are needed.

Aim:

To study the effectiveness of short-term triple therapy with amoxycillin, clarithromycin and either omeprazole or lansoprazole for eradication and healing of peptic ulcers.

Methods:

Patients with gastric or duodenal ulcers received amoxycillin (1 g b.d.), clarithromycin (500 mg b.d.) and lansoprazole (30 mg b.d.) (LAC) or omeprazole (20 mg b.d.) (OAC) for 7 days. Endoscopic examinations were performed before treatment and at least 4 weeks after completion of therapy. H. pylori status was confirmed by rapid urease test and histological examination (Giemsa stain) from gastric biopsies taken from both the antrum and the body.

Results:

A total of 356 patients were randomized in this single-blind study. On a per protocol basis, H. pylori was eradicated in 134 of 170 patients (79%) in the lansoprazole group and in 105 of 146 (72%) in the omeprazole group (P = 0.189); and in intention-to-treat analysis 72% and 62%, respectively (P = 0.043). Healing of the ulcers was obtained in 166 of 186 (98%), and in 139 of 146 patients (95%), respectively (P = 0.357). Side-effects occurred in two patients in the LAC group and in six in the OAC group B (four stopped therapy).

Conclusions:

This study has shown that the two regimens are highly effective in healing duodenal ulcers and are well tolerated. Neither treatment achieves the ideal cure rate for H. pylori. Lansoprazole does not appear to have a significant advantage over omeprazole either in ulcer healing or in H. pylori eradication.

     

Evaluation of short-term low-dose triple therapy for the eradication of Helicobacter pylori by factorial design in a randomized, double-blind, controlled study

Background

Studies demonstrating the efficacy of short-term low-dose triple therapies including omeprazole (O), clarithromycin (C) and a nitroimidazole (tinidazole, T) for Helicobacter pylori eradication have largely been open and uncontrolled, and have not assessed antibiotic sensitivity. Simpler regimens using the component drugs have not been evaluated.

Aim

To evaluate the OCT regimen in a randomized, controlled trial, testing for pre- and post-treatment antibiotic resistance and comparing, in a factorial design, the OCT regimen with simpler combinations of its components.

Methods

One hundred and twenty-eight patients (68 males, 60 females, age 22–80 years, mean 53 years) with H. pylori gastritis were randomly assigned to one of the following four treatment groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. + clari-thromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidazole 500 mg b.d.; (OCT) omeprazole 20 mg q.d.s. + clarithromycin 250 mg b.d. + tinidazole 500 mg b.d. The drugs were administered for 1 week. Medical interview, upper gastrointestinal endoscopy (with four antral and four corpus biopsies) and the ¹³C-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy specimens were used for the urease test, histology, and culture and sensitivities.

Results

All but one patient completed treatment. Side-effects were rare and mild in all groups. The eradication rate was 93.8% in group OCT, 59.4% in group CT, 31.3% in group OC and 6.3% in group C. Pre-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% and, to both antibiotics, 2.1%. In patients with pre-treatment metronidazole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Post-treatment resistance to clarithromycin was induced in 28.5% of the failures in group C, but in none of group OC. Resistance to both antibiotics occurred in 22.2% of the failures in group CT and in none of group OCT.

Conclusions

(i) The high efficacy of the OCT regimen is proved and each of the individual components of the regimen is essential to the result, possibly via a synergistic effect. (ii) Pre-treatment metronidazole resistance is scarcely relevant to the outcome. (iii) Acquired resistance is essentially nil if omeprazole is part of the regimen.

     

Equally high efficacy of 4, 7 and 10-day triple therapies to eradicate Helicobacter pylori infection in patients with ulcer disease

BACKGROUND: In patients with ulcer disease the optimal dose and duration of Helicobacter pylori treatment containing omeprazole (O), metronidazole (M) and clarithromycin (C) has yet to be established. The efficacy might be influenced by metronidazole- and clarithromycin-resistance. AIM: To study the effect of duration of OMC treatment on its efficacy and influence of metronidazole-resistance and clarithromycin-resistance on the optimal duration. MATERIALS AND METHODS: Ulcer patients (n=76) were randomized to three double-blind treatments of 10 days: OMC 4 consisted of 4 days b.d. 20 mg omeprazole, 400 mg metronidazole and 250 mg clarithromycin switched over to 6 days b.d. 20 mg omeprazole and placebo antibiotics (n=27); OMC 7 consisted of 7 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg and 3 days b.d. omeprazole 20 mg and placebo antibiotics (n=25); OMC 10 consisted of 10 days b.d. omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (n=24). H. pylori was assessed by biopsies for culture and histology pre- and 4-6 weeks after OMC therapy. Metronidazole-resistance and clarithromycin-resistance were assessed by the E-test. RESULTS: Intention-to-treat-eradication rates were: OMC 4, 96%; OMC 7, 92%; and OMC 10, 96% (N.S.). All of the three per protocol eradication rates were 100% (95% CI: 85.2-100). Of 75 isolates, 16 were metronidazole-resistant and one was clarithromycin-resistant. CONCLUSION: In H. pylori-positive ulcer patients, OMC 4 is highly efficacious and as effective as OMC 7 and OMC 10. No influence of metronidazole-resistance or clarithromycin-resistance was observed.     

Short report: treatment of Helicobacter pylori-associated duodenal ulcer with omeprazole plus antibiotics

Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common. Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse. This study investigates the effect of omeprazole with antibiotics in H. pylori-associated duodenal ulceration. Forty-three patients with endoscopically proven duodenal ulcer and H. pylori entered this study. Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. Four weeks after completing the treatment, 81 % (35143) had a healed duodenal ulcer, and 58% (25/43) had H. pylori eradication. In those who healed, at one year 21 remained H. pylori-negative, 12 had persistent H. pylori infection and 2 had re-infection. The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H. pylori-negative. This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer replase than omeprazole alone.     

Short Report: omeprazole-tetracycline combinations are inadequate as therapy for Helicobacter pylori infection

Background: Current triple antimicrobial therapies cure Helicobacter pylori infection in 60–90% of cases but are cumbersome. Addition of omeprazole to amoxycillin has been shown to enhance effectiveness when compared to amoxycillin alone Method: We studied omeprazole 20 mg t.d.s. plus tetracycline 500 mg q.d.s. for 14 days (OMP/TCN) and omeprazole 40 mg in the morning plus tetracycline 500 mg q.d.s. along with bismuth subsalicylate tablets 2 q.d.s. (OMP/TCN/BSS) for 14 days. Forty-four patients (19 OMP/TCN, 25 OMP/TCN/BSS) with H. pylori peptic ulcer disease were studied. H. pylori status was evaluated at least 4 weeks after ending antimicrobial therapy. Results: In the OMP/TCN group cure of H. pylori infection was achieved in 5/19 (26%). Adding bismuth to the regimen improved the results; 4 weeks after ending therapy cure of H. pylori infection was achieved in 12/25 (48%). Conclusions: Neither regimen can be recommended for routine cure of H. pylori infection. Although one cannot predict which antimicrobial therapies will be enhanced by the addition of omeprazole, these data suggest that future studies should evaluate drugs whose effectiveness is compromised by low pH.