A new quadruple therapy for Helicobacter pylori using tripotassium dicitrato bismuthate, furazolidone, josamycin and famotidine

BACKGROUND: In our previous study, a triple therapy using tripotassium dicitrato bismuthate (TDB), josamycin and furazolidone achieved a suboptimal cure rate of Helicobacter pylori infection. AIM: To investigate whether the addition of an antisecretory agent raises the cure rate using this regimen. METHODS: One hundred and twenty H. pylori positive patients with peptic ulcer disease or functional dyspepsia were randomly assigned to receive 1-week quadruple therapy of TDB 240 mg b.d., furazolidone 100 mg b.d., josamycin 1000 mg b.d. and famotidine 20 mg b.d. (BFJF group), or triple therapy of TDB 240 mg b.d., furazolidone 100 mg b.d. and clarithromycin 250 mg b.d. (BFC group). H. pylori status was assessed by histology and culture of gastric biopsy specimens before and at least 4 weeks after completion of therapy. RESULTS: Seven patients (three in the BFJF group and four in the BFC group) dropped out. Eradication rates (intention-to-treat/per protocol) were 90%/95% in the BFJF group and 82%/88% in the BFC group, respectively (P > 0.05). Duodenal ulcer healing rates were 94% (16/17) in the BFJF group and 80% (20/25) in the BFC group, respectively (P > 0.05). Mild side-effects occurred in 11 (18%) patients in the BFJF group and 10 (17%) in the BFC group (P > 0.05). CONCLUSIONS: One-week quadruple therapy consisting of TDB, furazolidone, josamycin and famotidine achieves a high cure rate of H. pylori infection.     

A seven-day Helicobacter pylori treatment regimen using clarithromycin, omeprazole and tripotassium dicitrato bismuthate.

AIM: To evaluate clarithromycin 500 mg t.d.s., tripotassium dicitrato bismuthate 240 mg b.d. and omeprazole 20 mg b.d. for 7 days as a Helicobacter pylori treatment regimen. METHODS: The H. pylori status of dyspeptic patients undergoing endoscopy was assessed by histology, culture and rapid urease testing of biopsies and by 13C-urea breath test. Fifty patients who were H. pylori-positive were treated with the above treatment regimen for 7 days. Those patients with active duodenal ulcers present at endoscopy were given omeprazole 20 mg nocte for a further 21 days. Not less than 28 days after completing treatment, all tests were repeated to reassess H. pylori status. Bacterial sensitivity of H. pylori cultures was determined and patients recorded any side- effects. RESULTS: On an intention-to-treat basis, H. pylori infection was cured in 90% (95% CI: 78-96%) of patients. Taste disturbance was experienced by 35% patients. Compliance was excellent, with 96% patients taking more than 95% of tablets. Metronidazole resistance was 41% but all cultures were sensitive to clarithromycin. CONCLUSIONS: This 7-day treatment achieved a high level of cure of H. pylori infection with relatively minor side-effects. It may have a role to play, particularly where there is a high level of metronidazole resistance.     

Helicobacter pylori infection treated with a tripotassium dicitrato bismuthate and metronidazole combination

Seventy-two patients with H. pylori infection in their antral mucosa took part in the study. Forty-three received metronidazole 400 mg t.d.s. for two weeks, plus De-Nol tabs 2 b.d. for four weeks, and the remaining 29 patients received metronidazole 400 mg t.d.s. for two weeks plus De-Nol liquid 5 ml q.d.s. for four weeks. Seven of 57 H. pylori isolates were found to have pre-treatment metronidazole resistance. Success, in terms of eradication of H. pylori, was assessed using a one-month post-treatment 14C urea breath test. Successful eradication of H. pylori was achieved in 72% and 79%, respectively, of the metronidazole/De-Nol tablet and metronidazole/De-Nol liquid groups. These figures increased to 87% and 84%, respectively, if the patients whose organisms were known to be metronidazole-sensitive were considered in isolation. H. pylori was successfully eradicated in only one of seven patients with a metronidazole-resistant organism.     

Helicobacter pylori: treatment with combinations of pivampicillin and tripotassium dicitrato bismuthate

Fifty Helicobacter pylori- (H. pylori) positive patients entered an open study and were assigned to one of four treatment regimens comprising: pivampicillin (500 mg b.d.) for 2 weeks +/- tripotassium dicitrato bismuthate (tablet or liquid form) for one month. The 14C-urea breath test was used to evaluate clearance (negative at the end of treatment) and eradication (negative at 1 month post-treatment) of H. pylori. Clearance rates were 20% (2/10) after pivampicillin alone, 86% (12/14) after tripotassium dicitrato bismuthate tablets (240 mg b.d.) plus pivampicillin, 67% (6/9) after tripotassium dicitrato bismuthate tablets (120 mg q.d.s.) plus pivampicillin, and 100% (13/13) after tripotassium dicitrato bismuthate liquid (120 mg in 5 ml q.d.s) plus pivampicillin. The eradication rates were 0% (0/10), 13% (2/15), 0% (0/11) and 54% (7/13), respectively. Combination of the results from the 2 tripotassium dicitrato bismuthate tablet/pivampicillin groups gave an eradication rate of 7.7% (2/26) which was significantly lower than the 53.9% (7/13) obtained with tripotassium dicitrato bismuthate liquid/pivampicillin (P less than 0.02). In conclusion, a liquid tripotassium dicitrato bismuthate pivampicillin combination may be of special use in the treatment of H. pylori-positive patients when triple therapy is contraindicated (e.g. patient sensitivity/allergy to metronidazole) or when the H. pylori isolate is resistant to metronidazole.     

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.     

Ranitidine bismuth citrate, tetracycline, clarithromycin twice-a-day triple therapy for clarithromycin susceptible Helicobacter pylori infection

BACKGROUND: Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success. AIM: To investigate the role of the new soluble form of bismuth, ranitidine bismuth citrate, in twice-a-day therapy for Helicobacter pylori infection. METHODS: Patients with histologically and culture proven H. pylori infection received ranitidine bismuth citrate 400 mg, tetracycline HCl 500 mg, and clarithromycin 500 mg, each b.d. for 14 days, followed by 300 mg ranitidine once a day for 4 additional weeks. Outcome was assessed 4 or more weeks after the end of antimicrobial therapy by repeat endoscopy with histology and culture (49 patients) or urea breath testing (14 patients). RESULTS: Sixty-three patients completed the therapy, 59 men and four women (average age 56.7 years; range 31-75 years). All patients had clarithromycin-susceptible strains prior to therapy. H. pylori infection was cured in 94% (95% CI: 85-98%). There was a therapy failure in one patient who took the medicine for only 1 day and stopped because of side-effects. Three of the isolates from treatment failures were available post-failure; two were clarithromycin-resistant and one was susceptible. Side-effects were severe in two patients (3%) and moderate in three (primarily diarrhoea). CONCLUSIONS: Twice-a-day ranitidine bismuth citrate, tetracycline, clarithromycin triple therapy was well tolerated and effective for the treatment of H. pylori infection in patients with clarithromycin-susceptible H. pylori.     

Does a previous course of tripotassium dicitrato bismuthate afect the subsequent chances of successful Helicobacter pylori eradication?

We have performed a retrospective study of 103 patients with either peptic ulcer or non-ulcer dyspepsia, infected with metronidazole-sensitive strains of Helicobacter pylori (H. pylori), who were treated with a combination of tripotassium dicitrato bismuthate and metronidazole for a period of at least two weeks. Dual therapy with tripotassium dicitrato bismuthate plus metronidazole showed similarly high eradication rates (greater than or equal to 80%) of H. pylori from patients irrespective of age, gender or clinical diagnosis. Most importantly, dual therapy achieved a similar eradication rate of H. pylori infection in 41 patients who had previously been treated with tripotassium dicitrato bismuthate alone or in combination with an antibiotic other than metronidazole. It therefore appears that H. pylori does not become resistant to treatment with tripotassium dicitrato bismuthate.     

One-week triple therapy with omeprazole, amoxycillin and clarithromycin for treatment of Helicobacter pylori infection

Background : Multi-drug regimens are generally required to reliably cure H. pylori infection. We previously demonstrated that a 2-week three-times-a-day regimen of amoxycillin and clarithromycin was effective against H. pylori infection.
Objectives : To evaluate the efficacy and side-effects of a 1-week twice-daily dosing schedule for the treatment of H. pylori infection.
Methods : We studied the efficacy of 1-week of therapy with 20 mg of omeprazole, 1 g of amoxycillin and 250 mg of clarithromycin, all twice daily H. pylori status was determined at entry and 4 or more weeks after completing antimicrobial therapy using histology (Genta stain) and culture.
Results : Thirty-one patients with documented peptic ulcer disease and H. pylori infection were treated. The H. pylori infection was cured in 24 (77%, 95% CI= 58–90%) (intention-to-treat). In a per protocol analysis the cure rate was 23 of 29 patients (79%, 95% CI= 60–92%). One patient took only 43% of the study drugs and another withdrew following development of an anaphylactic reaction to study medication. Mild side-effects were reported by 16% including diarrhoea, headache and altered taste. Compliance averaged 95%. Pretreatment clarithromycin resistance averaged 5% and had not been acquired by any strains post-therapy.
Conclusion : This combination of omeprazole, amoxycillin and low-dose clarithromycin resulted in a relatively low cure rate even in patients with clarithromycin-sensitive isolates. Large comparative studies will be needed to define the optimal duration, dose and dosing interval if this combination of drugs is to become competitive.     

Efficacy of low-dose clarithromycin triple therapy and tinidazole-containing triple therapy for Helicobacter pylori eradication

BACKGROUND: Proton pump inhibitor-based triple therapies are recommended as the first-line treatment for Helicobacter pylori eradication. AIM: To evaluate the efficacies of low-dose clarithromycin triple therapy and tinidazole-containing triple therapy in a metronidazole resistance prevalent area and to compare the efficacies with standard triple therapy. METHODS: In a randomized, multicentre, prospective study, a total of 352 patients with duodenal ulcer or non-ulcer dyspepsia were randomly divided into three groups according to the administered regimen: OAC250 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 250 mg), OAC500 group (omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg) and OTC group (omeprazole, 20 mg, tinidazole, 500 mg, and clarithromycin, 500 mg). The three groups received each regimen twice daily for 7 days. Upper gastrointestinal endoscopy was performed before and 4 weeks after treatment. H. pylori status was determined by rapid urease test and 13C urea breath test. RESULTS: The eradication rates in the OAC250, OAC500 and OTC groups were 76.2%, 65.7% and 64.8% (95% confidence interval: 67.9-84.4%, 56.7-74.8% and 55.7-73.9%), respectively, by intention-to-treat analysis (P=0.149) and 92.8%, 87.2% and 84.1% (95% confidence interval: 84.4-97.3%, 77.9-93.8% and 73.9-91.2%), respectively, by per protocol analysis (P=0.088). All regimens were well tolerated and compliance was excellent. CONCLUSIONS: Both low-dose clarithromycin triple therapy and tinidazole-containing triple therapy are effective and safe regimens for H. pylori eradication.     

One-week clarithromycin triple therapy regimens for eradication of Helicobacter pylori

Background:

One-week triple therapies have been endorsed as the treatment regimens of choice for eradication of Helicobacter pylori infection. Those that include clarithromycin appear to be the most effective.

Aim:

To review reports of triple therapies that include clarithromycin.

Methods:

Reports were identified from the literature to May 1998. The variation between study designs prevents a formal meta-analysis. A measure of the relative efficacies of regimens has, however, been gained by comparison and by pooling of intention-to-treat eradication rates.

Results:

One hundred and ninety-two studies were identified which included 264 treatment arms of a 1-week triple therapy composed of clarithromycin with amoxycillin or a nitroimidazole (metronidazole or tinidazole), and either ranitidine bismuth citrate or a proton pump inhibitor (omeprazole, lansoprazole or pantoprazole). From reports of these studies, an intention-to-treat H. pylori eradication rate could be determined from 210 treatment arms of 151 studies.

Conclusions:

There is little to choose between the efficacies of 1-week clarithromycin-based triple therapy eradication regimens. However, those comprising clarithromycin, a nitroimidazole and either ranitidine bismuth citrate or a high dose of omeprazole are, in general, the most effective. Against antibiotic-resistant strains of H. pylori, regimens including ranitidine bismuth citrate may be more effective than those including a proton pump inhibitor.

     

Rabeprazole, amoxycillin and low- or high-dose clarithromycin for cure of Helicobacter pylori infection

BACKGROUND: Rabeprazole sodium is a proton pump inhibitor. AIM: To evaluate the efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori. METHODS: A total of 100 subjects with H. pylori were randomly divided into two groups of 1-week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment. RESULTS: There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention-to-treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95% CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin-resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group. CONCLUSION: One-week triple therapy with rabeprazole, amoxycillin and low-dose clarithromycin is effective for the eradication of H. pylori infection.     

One-week triple therapy with esomeprazole,clarithromycin and metronidazole provides effective eradication of Helicobacter pylori infection

AIM: To compare the eradication rates of treatment with esomeprazole, metronidazole and clarithromycin (EMC) vs. omeprazole, metronidazole and clarithromycin (OMC), given for 7 days. OMC treatment was followed by 3 weeks of treatment with 20 mg omeprazole alone; the EMC group received placebo. METHODS: A randomized, double-blind, controlled study was conducted in 36 Canadian centres. Patients had a minimum 3-month history of dyspepsia, with or without a previous history of peptic ulcer disease, and were Helicobacter pylori positive by urea breath test. The eradication of H. pylori was determined by two negative breath tests performed at least 4 and 8 weeks following the completion of treatment. RESULTS: The intention-to-treat and per protocol populations consisted of 379 and 339 patients, respectively. The success rates of EMC/placebo were 76% (144/190) by intention-to-treat and 80% (138/172) by per protocol analysis; for OMC/omeprazole, the rates were 72% (137/189) and 75% (125/167), respectively. The difference between the two treatment groups was not significant. Treatment was well tolerated. CONCLUSIONS: A 7-day regimen of esomeprazole, metronidazole and clarithromycin is effective and well tolerated for the eradication of H. pylori infection.     

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.     

Short-term low-dose pantoprazole-based triple therapy for cure of Helicobacter pylori infection in duodenal ulcer patients

Background:

The eradication of Helicobacter pylori infection has been achieved using various therapy regimens, but the efficacy of the proton-pump inhibitor pantoprazole as part of these regimens has not yet been widely tested.

Aim:

To evaluate the efficacy and tolerability of a 1-week low-dose pantoprazole-based triple therapy in patients with H. pylori-positive duodenal ulcer.

Methods:

In an open single-centre prospective study, 71 patients with endoscopically proven active duodenal ulcer and H. pylori infection received pantoprazole 40 mg o.m. for 4 weeks, and during the first week a combination antimicrobial treatment comprising tinidazole 500 mg b.d. plus clarithomycin 250 mg b.d. H.?pylori eradication was defined as concordant negative histology and rapid urease test performed at endoscopy 4–6 weeks after the end of treatment, confirmed 4 weeks later by ¹³C-urea breath test.

Results:

Sixty-six patients (93%) completed the trial and five patients were lost to follow-up. H. pylori infection was cured in 61 out of the 66 patients who completed the trial (per-protocol analysis: 92.4%, 95% CI: 83.2–97.5%; intention-to-treat analysis: 85.9%, 95% CI: 75.7–93.0%). At final endoscopy, 65 out of 66 patients had healed ulcer (98.5%). Mild adverse events occurred in six patients (9.1%).

Conclusions:

One-week low-dose pantoprazole-based triple therapy is a simple, effective and well-tolerated regimen for ulcer healing and H. pylori eradication in patients with duodenal ulcer.

     

Efficacy and tolerability of a one-week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin for cure of Helicobacter pylori infection in patients with duodenal ulcer

Background : Previous studies have shown that one-week triple therapy consisting of omeprazole, clarithromycin and amoxycillin may cure Helicobacter pylori infection in the vast majority of patients. The present study was designed to test the hypothesis that a triple therapy with pantoprazole, clarithromycin and amoxycillin cures the infection in 80% of duodenal ulcer patients infected with H. pylori .
Methods : In an open two-centre study, 60 duodenal ulcer patients were treated with pantoprazole 40 mg b.d., clarithromycin 500 mg b.d. and amoxycillin 1 g b.d. for 1 week. During the second week patients received pantoprazole 40 mg once in the morning. We assessed H. pylori infection before treatment and 4 weeks after cessation of the study medication by a rapid urease test, histology after Warthin–Starry stain and a ¹³C-urea breath test.
Results : Sixty patients (42 males, mean age 47.4 years) entered the trial. All patients were infected with H. pylori . One patient was withdrawn from the study because of allergy to penicillin and six patients were protocol violators. H. pylori infection was cured in 47 out of 53 patients who completed the trial according to the protocol (89%; 95% CI: 80–97%) and in 49 of 60 patients included in the trial (82%; 95% CI: 72–92%). Four weeks after the last administration of study drugs, 55 out of 60 ulcers had healed (92%). Twenty-nine patients reported 51 adverse events that were mostly mild to moderate.
Conclusions : One-week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin is a simple and effective approach to the cure of H. pylori infection in patients with duodenal ulcer. In those patients who took the drugs as prescribed the H. pylori cure rate was 89%, with the lower 95% confidence limit being 80%.     

One week triple therapy with omeprazole, clarithromycin and tinidazole for Helicobacter pylori: differing efficacy in previously treated and untreated patients

Background : Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) has been found to be highly effective against Helicobacter pylori infection. However, its efficacy as a second line regimen for patients who failed metronidazole-based triple therapy has not been evaluated.
Aim : The aim of this study was to evaluate the efficacy of low-dose, short-term OCT therapy in an Israeli population, and to compare results obtained in previously treated and untreated patients.
Methods : Patients with duodenal or gastric ulcers and chronic antral gastritis with H. pylori infection as assessed by rapid urease test and/or ¹⁴C urea breath test (¹⁴C-UBT), were studied. All patients received omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. for 7 days. Eradication was assessed by ¹⁴C-UBT 4 weeks after treatment.
Results : One hundred and fourty-four patients (M/F=81/63) were enrolled (mean age 48.1 years, range 12–78). Eradication of H. pylori was significantly different between patients who were initially treated with this regimen (90/94, 96%) and patients who had previously failed to eradicate H. pylori with standard triple therapy (27/50, 54%). Moreover, the eradication rate was significantly decreased in patients with more than one previous failure (9/22, 41%) compared to that in patients with only one failure (18/29, 62%). No other differences such as age, gastric pathology, ethnic origin, smoking habits, or pre-treatment urease activity were found to influence the eradication rate.
Conclusions : One-week low-dose triple therapy with OCT is highly effective as an initial therapy in eradicating H. pylori infection. The efficacy is significantly lower when given as a second line treatment in patients who have previously failed to eradicate H. pylori with bismuth-based standard triple therapy.     

埃索美拉唑为基础的三联一线治疗幽门螺杆菌的疗效

目的 观察埃索美拉哗联合左氧氟沙星和阿莫西林一线治疗幽门螺杆菌的疗效.方法 163例幽门螺杆菌阳性患者,随机分为3组,分别应用埃索美拉唑20mg每13 2次(A组),埃索美拉唑40 mg每13 2次(B组),埃索美拉唑40 mg每日1次(C组),3组均加用左氧氟沙星500 mg每日1次和阿莫西林1000 mg每日2次,疗程7 d.并且对幽门螺杆菌根除率分别按意愿治疗(ITT)分析和方案(PP)分析进行评估.结果 A、B、C组各治疗方案的根除率:ITT法为82.98%、87.10%、70.37%;PP法为86.67%、88.52%,73.08%.B组明显高于C组(P<0.05).结论 埃索美拉唑联合左氧氟沙星和阿莫西林一线治疗能显著提高幽门螺杆菌根除率.