Effects of in vitro antibiotic resistance on treatment: bismuth-containing regimens.

Bismuth compounds remain useful for Helicobacter pylori eradication therapy. These include colloidal bismuth subcitrate (CBS), bismuth subsalicylate (BSS) and, most recently, ranitidine bismuth citrate (RBC). CBS appears to prevent the development of imidazole resistance when coadministered with nitroimidazoles. Traditional triple therapy with bismuth, metronidazole and tetracycline or amoxicillin (BMT/A) only partially overcomes metronidazole resistance. However, the addition of a PPI to bismuth triple therapy largely overcomes established metronidazole resistance if treatment is given for at least one week or more. When RBC rather than PPI is used with clarithromycin, this dual regimen appears to be more effective in preventing the development of secondary clarithromycin resistance. The triple combination of RBC, metronidazole and clarithromycin appears to be effective against metronidazole resistant strains of H pylori. Thus, overall, there is some evidence that bismuth compounds may prevent the development of antibiotic resistance and that existing antibiotic resistance may at least be partially overcome in vitro and in vivo. With the growing emergence of H pylori resistance to metronidazole and clarithromycin, further research to clarify the role of bismuth compounds is required.     

How to proceed in Helicobacter pylori-positive chronic gastritis refractory to first- and second-line eradication therapy

Helicobacter pylori is a widespread disease causing most of the peptic ulcer diseases and low-grade mucosa-associated lymphoreticular tissue (MALT) lymphoma. Moreover, H. pylori is a proven environmental risk factor for gastric carcinoma and it has been recognized as a type 1 carcinogen factor. A combination of drugs has been proposed, using a proton pump inhibitor (PPI), amoxicillin, clarithromycin, metronidazole and tetracycline to treat the infection. Since 1996, according to the European guidelines, the first-line approach using PPI, amoxicillin and clarithromycin or metronidazole has been suggested. Seven days of quadruple therapy with PPI (or ranitidine), tetracycline, bismuth salts and metronidazole has been reserved as second-line treatment. To improve the eradication rate of the triple therapy, a different combination of the available antibiotics has been proposed, consisting of a 10-day sequential regimen. A second-line levofloxacin-amoxicillin-based triple therapy given for 10 days has been proposed, obtaining a high eradication rate, suggesting this regimen to be a suitable retreatment option in eradication failure. A third-line treatment with rifabutin-based regimen has been proposed.     

Attitude facing a patient suffering from Helicobacter pylori infection resistant to a triple therapy.

Even with the current most effective treatment regimens, about 10-20% of patients will fail to eradicate H. pylori infection. Therefore, in designing a treatment strategy we should not focus on the results of primary therapy alone, but also on the final (over-all) eradication rate. The choice of a second-line treatment depends on which treatment was used initially, as retreatment with the same regimen is not recommended. In this respect, the first therapy should not be a regimen that combines clarithromycin and metronidazole in the same regimen, because of the problem of resistance against both antibiotics. Therefore, it seems that performing culture after a first eradication failure is not necessary and assessing H. pylori sensitivity to antibiotics only after failure of the second treatment may be suggested in clinical practice. Different possibilities of empirical treatment are suggested. After failure of proton pump inhibitor (PPI)-amoxicillin-clarithromycin, quadruple therapy has been generally used. More recently, replacing the PPI and the bismuth compound by ranitidine bismuth citrate (RBC) has also achieved good results. After PPI-amoxicillin-nitroimidazole failure, retreatment with PPI-amoxicillin-clarithromycin has proved to be effective. Finally, rifabutin-based rescue therapies have shown to constitute an encouraging strategy for eradication failures, as they are effective for H. pylori strains resistant to antibiotics.     

'Rescue' therapies for the management of Helicobacter pylori infection

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcer and gastric cancer and should be considered as a major public health issue. According to several international guidelines, first-line therapy for treating H. pylori infection consists of proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) with any two antibiotics of amoxicillin, clarithromycin or metronidazole given for 7-14 days. However, even with the recommended treatment regimens, approximately 20% of patients will fail to obtain H. pylori eradication. The proportion of patients with first-line H. pylori therapy failure may be higher in clinical practice and it may increase thanks to diffusion of H. pylori treatment. The recommended second-line therapy is the quadruple regimen composed by tetracycline, metronidazole, bismuth salts and a PPI. However, the efficacy of this regimen is limited by poor patient's compliance due to its side effects, number of tablets per day, and long duration. Moreover, bismuth and metronidazole are not available in all countries. Alternatively, a longer-lasting (i.e. 10-14 days) PPI or RBC triple therapy with two antibiotics has generally been used. In an empirical strategy, the choice of second line depends on the treatment initially used. If a clarithromycin-based regimen was administered in first line, a quadruple regimen or PPI (or RBC) triple therapy with metronidazole and amoxicillin (or tetracycline) should be suggested as a second line. In case of second-line treatment failure, the patient should be evaluated by a case-by-case approach. A susceptibility-guided strategy, if available, is recommended in order to choose the best third-line treatment. Culture can reveal the presence of H. pylori-sensitive strains to clarithromycin (the best effective) or other antimicrobials (such as amoxicillin, metronidazole and tetracycline). Conversely, in an empirical strategy, a third-line not yet used therapy, can reach a high success rate. PPI or RBC, amoxicillin and a new antimicrobial (e.g. rifabutin, levofloxacin or furazolidone) could be used. Several studies have obtained relatively good results with triple therapy combining PPI, rifabutin, and amoxicillin, although a reversible myelotoxicity as leukopenia and thrombocytopenia has been described. Preliminary good results were also achieved with triples PPI regimens combining levofloxacin and amoxicillin without important adverse effects. Furazolidone has also shown efficacy for H. pylori eradication, although untoward reactions could limit its use, especially when high doses are employed. Finally, in more than one H. pylori treatment failure, non-antimicrobial add-on medications (such as lactoferrin, probiotics and others) could be used with the aim either to improve the eradication rate or to minimize side effects.     

Duodenal ulcer healing rates in a one-year follow-up study with ranitidine bismuth citrate and antibiotics

BACKGROUND/AIMS: The aim of this study was to determine the one-year outcome of an eradication therapy with ranitidine bismuth citrate and antibiotics in Helicobacter pylori-positive duodenal ulcer patients in respect to ulcer and Helicobacter pylori relapse rates. METHODOLOGY: This multicenter, randomized, double-blind study involved 648 duodenal ulcer patients and had been carried out to compare the following regimens: ranitidine bismuth citrate b.i.d. co-prescribed with either clarithromycin 250 mg q.i.d. or clarithromycin 500 mg b.i.d. or clarithromycin 500 mg b.i.d. plus metronidazole 400 mg b.i.d. for 2 weeks, followed by a further 14 days of treatment with ranitidine bismuth citrate 400 mg b.i.d. to facilitate ulcer healing. H. pylori eradication was assessed by 13C-urea breath test and histology at least 4 weeks, 26 weeks and 52 weeks after the end of treatment. Ulcer relapse and H. pylori status were assessed 4 weeks, 26 weeks and 52 weeks post-treatment or if ulcer symptoms recurred. For the remainder of the follow-up period only serious adverse events were collected. RESULTS: At 12 months data of 438 (69%) patients were evaluable. The observed H. pylori eradication rates were 88-91%. H. pylori relapse rates were 2.1% after 26 weeks and 3.9% after 52 weeks. At the week 26 visit 26 patients (5.6%) and at the week 52 visit 25 patients (5.7%) had documented gastroesophageal reflux disease. CONCLUSIONS: Our data confirm the reduction of duodenal ulcer relapses after the cure of Helicobacter pylori infection.     

Third-line rescue therapy for Helicobacter pylori infection

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amo-xicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.     

Comparison of ranitidine bismuth citrate, tetracycline and metronidazole with ranitidine bismuth citrate and azithromycin for the eradication of Helicobacter pylori in patients resistant to PPI based triple therapy.

BACKGROUND/AIMS: Helicobacter pylori is the most common infectious disease all over the world. Ten to twenty percent of the patients remain infected despite treatment with proton pump inhibitors (PPIs), amoxicillin and clarithromycin. We compared PPI, bismuth, tetracycline and metronidazole with ranitidine bismuth citrate, tetracycline and metronidazole in cases resistant to PPIs-based triple therapies. METHODS: The study included 52 patients who underwent a triple therapy with PPI, clarithromycin and amoxicillin for 14 days between September 2001 and December 2002, and were found to be resistant to the therapy. They were randomized to take ranitidine bismuth citrate (Rb) 400 mg twice a day, tetracycline (T) 1 g twice a day and metronidazole (M) 500 mg three times a day for 14 days (RbTM), or ranitidine bismuth citrate (Rb) 400 mg twice a day for 14 days and azithromycin (A) 500 mg once a day for 7 days (RbA). Four weeks after the treatment, endoscopies were repeated, and patients were assessed with respect to changes in symptoms. When H. pylori was negative on histological analysis and urease test, eradication was achieved. RESULTS: A total of 52 patients, 32 females and 20 males with a mean age of 49+/-12 years, were included in the study. Eradication was achieved in 15 (28%) out of 52 patients in total. There was a significant difference between RbA and RbTM groups (p=0.01). In fact, H. pylori was eradicated in 3 (12%) out of 25 patients in the RbA group, whereas it was eradicated in 12 (44.4%) out of 27 patients in the RbTM group. Symptom scores significantly improved in both groups after the treatment, though there was not a significant difference between the groups (p=0.705). CONCLUSIONS: Triple therapy including azithromycin does not seem to be a good choice in cases resistant to the first line therapies; however, a similarly lower rate of eradication was achieved with the quadruple therapy proposed. Therefore, different treatment schemes should be applied in resistant patients, and further studies are needed as well.     

Helicobacter pylori eradication therapy is more effective in peptic ulcer than in non-ulcer dyspepsia.

AIM: To evaluate whether eradication therapy is more effective in peptic ulcer disease (PUD) than in non-ulcer dyspepsia (NUD). METHODS: We retrospectively studied 481 patients with NUD (183 patients) or PUD (298 patients) infected with Helicobacter pylori included in several prospective clinical trials. Three eradication regimens were given: (1) proton pump inhibitor (PPI) plus clarithromycin, plus either amoxycillin or metronidazole for 7 days (297 patients); (2) ranitidine bismuth citrate (RBC) plus clarithromycin plus amoxycillin for 7 days (79 patients); and (3) RBC plus clarithromycin plus amoxycillin plus metronidazole for 5 days (105 patients). H. pylori eradication was defined as a negative 13C-urea breath test 4 weeks after completing treatment. RESULTS: H. pylori eradication rates were 82% (95% CI 78-87%) with PPI plus two antibiotics for 7 days, 85% (95% CI 75-91%) with RBC plus two antibiotics for 7 days, and 91% (95% CI 86-97%) with RBC plus three antibiotics for 5 days (P < 0.05 compared with the first regimen). Overall, the H. pylori eradication rate in patients with NUD was 78% (95% CI 71-84%), while in patients with PUD it was 89% (95% CI 86-93%) (P < 0.001). Both the combination of PPI plus two antibiotics for 7 days and the combination of RBC plus three antibiotics for 5 days were more effective in PUD than in NUD patients. However, RBC plus clarithromycin plus amoxycillin for 7 days was equally effective in both diseases. RBC plus two antibiotics for 7 days achieved better results than the same therapy with PPI only in NUD patients (84% v. 59%, P < 0.01), but both regimens were similar when prescribed in PUD patients (86% v. 88%). In the multivariate analysis, the type of therapy, the diagnosis (NUD v. PUD), and the product variable of therapy (with RBC plus 2 antibiotics for 7 days) and diagnosis (interaction variable) were the only variables that influenced H. pylori eradication. The odds ratio (OR) for the effect of RBC versus PPI plus two antibiotics for 7 days in patients with NUD was 4 (95% CI 1.7-9.7; P < 0.01), whereas in patients with PUD no statistical significance was achieved (OR 0.79; 95% CI 0.2-3.9). CONCLUSION: Overall, H. pylori eradication therapy is more effective in PUD than in NUD patients. This advantage of eradication therapies in PUD patients seems to be observed with 7-day PPI-based triple regimens, and with 5-day RBC-based quadruple therapy, while the 7-day RBC-based triple regimen seems to be equally effective in both diseases.     

One-week ranitidine bismuth citrate versus colloidal bismuth subcitrate-based anti-Helicobacter triple therapy: a prospective randomized controlled trial

OBJECTIVE: The efficacy of 1 wk bismuth triple therapy is adversely influenced by the presence of metronidazole resistance. In vitro studies suggest that ranitidine bismuth citrate (RBC) plus metronidazole exhibit synergistic activity against metronidazole resistant strains of Helicobacter pylori (H. pylori). Whether this confers a superior clinical efficacy remains unproven. This study compared the efficacy of RBC-based triple therapy with bismuth triple therapy in eradication of H. pylori. METHODS: Patients with H. pylori-related ulcer disease or gastritis were randomized to receive either 400/mg of RBC twice daily plus 400/mg of metronidazole and 500/mg of tetracycline four times daily for 1 wk (RMT) or 120/mg of colloidal bismuth subcitrate, 400/mg of metronidazole, and 500/mg of tetracycline, all given four times daily for 1 wk (BMT). Metronidazole susceptibility was determined by the E-test and pretreatment resistance was defined as minimum inhibitory concentration > or = 32/mg/L. RESULTS: Of 100 consecutive patients randomized, two patients were lost to follow-up in each group. Forty-three of 85 (51%) H. pylori isolates were metronidazole resistant. Per-protocol cure rate for RMT and BMT was 40 of 41 (98%) and 37 of 44 (84%), respectively (p = 0.058). Intent-to-treat cure rate for RMT and BMT was 46 of 50 and 41 of 50, respectively (92% vs 82%, p = 0.23). A significantly higher eradication of metronidazole resistant H. pylori was observed in the RMT group (25 of 25, 100%) than in the BMT group (12 of 16, 75%), (p = 0.018). Side effects observed in the two treatment groups were comparable. CONCLUSIONS: One week of RBC triple therapy with metronidazole and tetracycline is an effective anti-Helicobacter therapy. This regimen is more appropriate in areas of high prevalence of metronidazole resistance.     

Update on therapeutic options for <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-related diseases

Triple therapy including clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) has been recommended as the treatment of choice for Helicobacter pylori eradication. This regimen is now challenged by an increasing level of clarithromycin resistance that jeopardizes the treatment success. When clarithromycin resistance has been detected, or when its rate is known to be high in the geographic area, this drug cannot be used. It can be replaced by metronidazole, the resistance of which has a limited clinical relevance. Another option is to prescribe tetracycline and metronidazole with a PPI or ranitidine bismuth citrate. New antibiotics such as levofloxacin or rifabutin can also be used in combination with amoxicillin and a PPI. Probiotics can be added to all of these regimens to improve compliance by decreasing adverse events. But some authors advocate a quadruple therapy as a first-line treatment. Solutions to improve the limitations of this last regimen are now being proposed. Clarification of the controversial treatment indications such as gastroesophageal reflux disease or prevention of nonsteroidal anti-inflammatory drug gastroduodenal symptoms has been made. The question of prevention of gastric carcinoma by H. pylori eradication remains unanswered.     

Treatment of <Emphasis Type="Italic">helicobacter pylori</Emphasis> eradication failures

Opinion statement Even with the current most effective treatment regimens, about 10% to 20% of patients will fail to eradicate Helicobacter pylori infection. Therefore, in designing a treatment strategy, we should not focus on the results of primary therapy alone but also on the final (overall) eradication rate. The choice of a second-line treatment depends on which treatment was used initially, because retreatment with the same regimen is not recommended. Therefore, it seems that performing culture after a first eradication failure is not necessary and assessing H. pylori sensitivity to antibiotics only after failure of the second treatment is suggested in clinical practice. Different possibilities of empirical treatment are suggested. After failure of proton pump inhibitor (PPI)-amoxicillin-clarithromycin, quadruple therapy has been generally used. More recently, replacing the PPI and the bismuth compound by ranitidine bismuth citrate has also achieved good results. After PPI-amoxicillin-nitroimidazole failure, retreatment with PPI-amoxicillin-clarithromycin has proved to be effective. Finally, the first therapy should not combine clarithromycin and metronidazole in the same regimen because of the problem of resistance against both antibiotics. Recently, rifabutin-based rescue therapies have been shown to constitute an encouraging strategy for eradication failures because they are effective for H. pylori strains resistant to antibiotics.     

One-week dual therapy with ranitidine bismuth citrate and clarithromycin for the treatment of Helicobacter pylori infection in Brazilian patients with peptic ulcer

AIM: To assess the efficacy and safety of ranitidine bismuth citrate plus clarithromycin given for 1 wk in Brazilian patients with peptic ulcer. METHODS: One hundred and twenty patients with peptic ulcer were randomized in two treatment groups: (1)1-wk regimen consisting of ranitidine bismuth citrate 400 mg b.i.d. with clarithromycin 500 mg b.i.d. or (2) 2-wk regimen of the same treatment. Eradication of the infection was considered when both the histologic examination and the urease test were negative for the infection 3 mo after treatment. RESULTS: By intention to treat analysis, Helicobacter pylori (H pylori) was eradicated in 73% and 76% of patients, respectively treated for 1 or 2 wk (P>0.05). By per protocol analysis, the eradication rates were 80% and 83%, respectively, in patients treated for 1 or 2 wk (P>0.05). Nine patients (8.2%) reported minor side effects. CONCLUSION: One-week therapy with ranitidine bismuth citrate and clarithromycin is safe, well tolerated and effective for treatment of H pylori infection, and appears to be comparable to the 2-wk regimen in terms of efficacy.x     

Ranitidine bismuth citrate.

Recognition of the relationship between Helicobacter pylori infection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications of H pylori infection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC), a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicating H pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole) is advocated as the treatment of choice for H pylori eradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment of H pylori infection. Bismuth levels do not appear to rise to toxic levels.     

Helicobacter Pylori

Opinion Statement All infected patients with a peptic ulcer should be treated for H. pylori. The role of treating H. pylori in patients with undiagnosed dyspepsia or non-ulcer dyspepsia, those taking nonsteroidal anti-inflammatory medications, or with a family history of gastric cancer remains controversial. Triple therapies consisting of a proton pump inhibitor or ranitidine bismuth citrate and two antibiotics are the current standard of therapy for H. pylori. In general, dual therapies should no longer be used to treat H. pylori. Bismuth triple therapy consisting of bismuth, tetracycline, and metronidazole is a less expensive alternative to proton pump inhibitor-or ranitidine bismuth citrate-based triple therapies. However, bismuth triple therapy is hampered by frequent side effects and the need for qid dosing. In Europe, a 7-day course of therapy appears to be adequate. In the United States, 10-14 days of therapy are currently recommended. Metronidazole resistance in H. pylori strains varies geographically, and negatively influences the effectiveness of therapies containing this antibiotic. Clarithromycin resistance is relatively infrequent at the current time but may be rising in countries where this antibiotic is in use. If a patient remains infected after a course of therapy for H. pylori, the second treatment should avoid the antibiotics used initially.     

Various durations of a standard regimen (amoxycillin, metronidazole, colloidal bismuth sub-citrate for 2 weeks or with additional ranitidine for 1 or 2 weeks) on eradication of Helicobacter pylori in Iranian peptic ulcer patients. A randomized controlled trial

INTRODUCTION: One of the most economical and effective therapeutic regimens for eradication of Helicobacter pylori is the classic triple therapy with amoxycillin or tetracycline, metronidazole and a bismuth derivative. Addition of H2-receptor antagonists to these drugs may heighten the rate of eradication and shorten the duration. We therefore performed a randomized controlled trial comparing twice daily metronidazole, bismuth derivative and amoxycillin for 2 weeks with additional ranitidine for 1 or 2 weeks. PATIENTS AND METHODS: In total, 240 adult patients with duodenal ulcer and H. pylori infection were randomly assigned to one of the following regimens: (1) amoxycillin 1 g bid, metronidazole 500 mg bid, bismuth sub-citrate 240 mg bid and ranitidine 300 mg bid for 1 week; (2) triple therapy without ranitidine for 2 weeks; or (3) triple therapy plus ranitidine 300 mg bid for 2 weeks. Side-effects of the drugs were evaluated two weeks after starting the treatment. The rapid urease test and histology from antrum and corpus, and/or 14C- urea breath test were used to determine H. pylori eradication six weeks after starting the treatment. RESULTS: In total, 195 patients were followed up for 6 weeks. The most frequent drug side-effects were unpleasant taste (46%), dry mouth (41%) and fatigue (26%), which had an equal distribution in all treatment groups. Endoscopy and 14C- urea breath test were performed for 178 and 123 patients, respectively. Eradication of H. pylori was documented in 19/64 (29.7%), 29/63 (46%) and 50/68 (73.5%) of patients in groups 1, 2 and 3, respectively (P < 0.000001 for group 1 versus group 3; P < 0.0014 for group 2 versus group 3; difference not significant for group 1 versus group 2). An intention-to-treat analysis showed eradication rates of 19/80 (23.75%), 29/80 (36.25%) and 50/80 (62.5%) for groups 1, 2 and 3, respectively. At four weeks post-treatment, the most sensitive test for evaluation of eradication of H. pylori was histology. CONCLUSION: Although combined use of an H2-receptor antagonist and twice daily triple therapy in a two-week regimen is more effective than two-week triple or one-week quadruple therapy in Iranian patients, none of these regimens is ideal in countries with a probable high rate of resistant and strongly toxic strains of H. pylori.     

Evaluation of triple and quadruple Helicobacter pylori eradication therapies in Iranian children: a randomized clinical trial

BACKGROUND: Clinical trials in children concerning Helicobacter pylori eradication treatments are scarce. The purpose of this study was to assess the efficacy of proton pump inhibitor (PPI)-based triple therapy using PPI, amoxicillin and clarithromycin in Iranian children. We also evaluated the efficacy of quadruple therapy with PPI, metronidazole, amoxicilin and bismuth citrate in Iranian children. METHODS: This was a randomized clinical trial performed in Emam Khomeini Hospital between 2003 and 2004. Patients with confirmed H. pylori infection by histology were divided into two groups in a randomized 1:1 scheme: the triple regimen group (omeprazole, clarithromycin and amoxicillin for 10 days) and the quadruple regimen group (omeprazole, amoxicillin, metronidazole and bismuth citrate for 10 days). The eradication was assessed by the C-urea breath test 4 weeks after the end of treatment and analyzed by per-protocol and intention-to-treat approaches. RESULTS: One hundred and twenty-two patients (mean age 12.36+/-3.06 years) were entered into the study. Only 100 patients completed the study (50 patients in each regimen group). The eradication rates by triple therapy were 92% and 75.5% for the "per-protocol" and "intention-to-treat" approaches, respectively. In the quadruple regimen group, the eradication rates were 84% by the per-protocol approach and 68.8% in the intention-to-treat approach. Symptom responses to therapy were reported in all patients with successful eradication (88% of all patients). CONCLUSION: With regard to recent recommendations, we also suggest PPI, amoxicillin and clarithromycin triple therapy as a first-line eradication treatment, and quadruple therapies as a second-line option, in Iranian children.     

Ranitidine bismuth citrate or omeprazole-based triple therapy for Helicobacter pylori eradication in Helicobacter pylori- infected non-ulcer dyspepsia

AIM: To test the eradication rate of Helicobacter pylori by ranitidine bismuth citrate-based triple therapy, and evaluate the symptomatic response of Helicobacter pylori eradication therapy for non-ulcer dyspepsia. METHODS: A total of 59 consecutive Helicobacter pylori infected non-ulcer dyspepsia patients were randomly selected to receive either one of two triple therapy regimens, including metronidazole, amoxycillin plus ranitidine bismuth citrate (RAM group) or omeprazole (OAM group). To determine the success of eradication, patients underwent the 13C-urea breath test, 6 weeks and one year after treatment. The dyspeptic symptom scores were also assessed at the time of enrolment, 6 weeks and one year after treatment. RESULTS: Per-protocol and intention-to-treat eradication rates were 77.7% and 70% in RAM group and 83.8% and 68.9% in OAM group (p = non significant). At both the 6th week and at the first year after treatment, the mean symptom scores were lower than pre-treatment scores in the study population, regardless of whether treatment was successful or not. However, patients, whether eradicated successfully or not-eradicated, presented similar 6-week and 1-year scores. CONCLUSIONS: One-week RAM triple therapy, which is cheaper than the OAM regimen, is a relatively effective alternative regimen for Helicobacter pylori eradication in Taiwanese. Triple therapy for Helicobacter pylori eradication was not the whole management for the relief of dyspeptic symptoms of non-ulcer dyspepsia patients.     

Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study).

BACKGROUND: Short-term therapies for eradicating Helicobacter pylori in selected patients might offer advantages in terms of costs, compliance, and adverse effects in contrast to standard 1-week triple therapy. METHODS: To determine eradication success and influencing factors in a new short-term quadruple therapy, a total of 243 patients positive for H pylori were randomly assigned to 1 of 3 regimens according to age, smoking status, and diagnosis: a 5-day treatment with 3 antibiotics (amoxicillin, 1 g twice daily [bid]; clarithromycin, 250 mg bid; and metronidazole, 400 mg bid) and lansoprazole (30 mg bid [L5; reference treatment]) or ranitidine hydrochloride (300 mg bid [R5]), or the same 3-day antibiotic-lansoprazole combination (L3) with a 2-day pretreatment with lansoprazole. RESULTS: A total of 234 patients completed the study. On an intention-to-treat basis, overall eradication of H pylori was confirmed in 86.4%: 89.2% in the L5 group vs 81.2% in the L3 group vs 88.8% in the R5 group; differences were not significant. Multiple logistic regression analysis showed that younger age (<55 years; P =.03), history of peptic ulcer disease (P =.04), smoking (P =.03), metronidazole resistance (P =.003), low ranitidine trough serum concentrations (P =.005), cytotoxin-associated gene A-negative strains in peptic ulcer disease (P =.04), and outer inflammatory protein A-positive strains (P =.02) were associated with eradication failure. CONCLUSIONS: This new quadruple H pylori eradication regimen is efficacious, safe, well tolerated, and cost saving, and may be a treatment option for patients older than 55 years with no history of peptic ulcer disease. Furthermore, strains that are sensitive to all antibiotics, cytotoxin-associated gene A-positive, and outer inflammatory protein A-negative could be suitable for short-term quadruple therapy. Patients with an unfavorable combination of characteristics should be treated for a minimum of 7 days.     

Helicobacter pylori infection and antimicrobial agents resistance

PURPOSE: Seven days triple therapies combining a proton pump inhibitor (PPI) and 2 antimicrobial agents (clarithromycin [C], amoxicillin [A], metronidazole [M]), are recommended for the treatment of Helicobacter pylori infection. The eradication failures have increased these last years, particularly in France (about 30%). They are essentially related to the development of antimicrobial agents resistance, mainly concerning macrolides and nitro-imidazoles. CURRENT KNOWLEDGE AND KEY POINTS: Primary resistance to clarithromycin is variable, but reaching now about 10% throughout the world and about 20% in France. It reduces the eradication success rate at 25%. The secondary resistance is very high, contra-indicating the use of clarithromycin in second line regimens. Primary resistance to amoxicillin has recently appeared, but remains very low until now, less than 2%, as the tetracyclin (T) resistance. Primary resistance to metronidazole is 3 times higher than macrolides resistance, but its determination is less accurate. Metronidazole resistance reduces eradication rate of about 25%, leading to the use of metronidazole in second line therapy, in increasing the triple therapy duration at 14 days (PPI-A-M), or in combination with quadruple therapy (Bismuth-PPI-T-M). Other rescue-treatments are efficacious, based on ranitidine bismuth citrate combined regimens or on rifabutine (R) based regimens (PPI-A-R). FUTURE PROSPECTS AND PROJECTS: The recent knowledge of the mutations mainly responsible for H. pylori resistance to antimicrobial agents now allows the development of detection methods based on the study of bacterial DNA. These methods have been validated for clarithromycin and should favour in the near future the determination of resistance by the use of biopsy culture or directly on the gastric biopsy.     

Treatment of Helicobacter pylori infection

Helicobacter pylori is a serious, chronic, progressive, and transmissible infection associated with a significant morbidity and mortality, which alone emphasizes the priority of developing adequate prophylactic or therapeutic measures. What was previously termed "asymptomatic H. pylori infection" is now recognized as a latent infection, and it is now accepted that the presence of an H. pylori infection is an indication for eradication therapy. Successful cure of H. pylori infection requires 2 or more antibiotics. Antibiotic resistance is the major impediment of cure. The ideal duration of therapy is unknown, but in general, 1 week therapy is less effective than longer durations. Compliance is important for the success of treatment; therefore, the favored regimen should have the least side effects. At present, a proton pump inhibitor (or ranitidine bismuth citrate)-clarithromycin triple therapy with either amoxicillin or metronidazole, for at least 10 days is considered first-line therapy. The alternative is quadruple therapy containing a proton pump inhibitor, bismuth, tetracycline, and a higher dose of metronidazole. Quadruple therapy is the best choice after failure of proton pump inhibitor-clarithromycin triple therapy. Confirmation of successful therapy with a urea breath test or a stool antigen test is now the standard of practice.