Pretreatment with Ranitidine Bismuth Citrate May Improve Success Rates of Helicobacter pylori Eradication: A Prospective, Randomized, Controlled and Open-Label Study.

Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.

Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters.

SARS-CoV-2 is causing a pandemic of COVID-19, with high infectivity and significant mortality1. Currently, therapeutic options for COVID-19 are limited. Historically, metal compounds have found use as antimicrobial agents, but their antiviral activities have rarely been explored. Here, we test a set of metallodrugs and related compounds, and identify ranitidine bismuth citrate, a commonly used drug for the treatment of Helicobacter pylori infection, as a potent anti-SARS-CoV-2 agent, both in vitro and in vivo. Ranitidine bismuth citrate exhibited low cytotoxicity and protected SARS-CoV-2-infected cells with a high selectivity index of 975. Importantly, ranitidine bismuth citrate suppressed SARS-CoV-2 replication, leading to decreased viral loads in both upper and lower respiratory tracts, and relieved virus-associated pneumonia in a golden Syrian hamster model. In vitro studies showed that ranitidine bismuth citrate and its related compounds exhibited inhibition towards both the ATPase (IC50 = 0.69 µM) and DNA-unwinding (IC50 = 0.70 µM) activities of the SARS-CoV-2 helicase via an irreversible displacement of zinc(II) ions from the enzyme by bismuth(III) ions. Our findings highlight viral helicase as a druggable target and the clinical potential of bismuth(III) drugs or other metallodrugs for the treatment of SARS-CoV-2 infection.

Synthesis and biological evaluation of ranitidine analogs as multiple-target-directed cognitive enhancers for the treatment of Alzheimer's disease.

Using molecular modeling and rationally designed structural modifications, the multi-target structure-activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydrophobic and π-π interactions with the peripheral anionic site of the AChE active site. The SAR of a series of cyclic imides demonstrated that AChE inhibition is increased by additional aromatic rings, where 1,8-naphthalimide derivatives were the most potent analogs and other key determinants were revealed. In addition to improving AChE activity and chemical stability, structural modifications allowed determination of binding affinities and selectivities for M1-M4 receptors and butyrylcholinesterase (BuChE). These results as a whole indicate that the 4-nitropyridazine moiety of the JWS-USC-75IX parent ranitidine compound (JWS) can be replaced with other chemotypes while retaining effective AChE inhibition. These studies allowed investigation into multitargeted binding to key receptors and warrant further investigation into 1,8-naphthalimide ranitidine derivatives for the treatment of Alzheimer's disease.

A multicenter, randomized, prospective study of 14-day ranitidine bismuth citrate- vs. lansoprazole-based triple therapy for the eradication of Helicobacter pylori in dyspeptic patients.

BACKGROUND/AIMS: Proton-pump inhibitor and ranitidine bismuth citrate-based triple regimens are the two recommended first line treatments for the eradication of Helicobacter pylori. We aimed to compare the effectiveness and tolerability of these two treatments in a prospective, multicentric, randomized study. MATERIALS AND METHODS: Patients with dyspeptic complaints were recruited from 15 study centers. Presence of Helicobacter pylori was investigated by both histology and rapid urease test. The patients were randomized to either ranitidine bismuth citrate 400 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=149) or lansoprazole 30 mg bid plus amoxicillin 1 g bid plus clarithromycin 500 mg bid (n=130) treatment arm for 14 days. Adverse events have been recorded during the treatment phase. A 13 C urea breath test was performed 6 weeks after termination of treatment to assess the efficacy of the therapy. Eradication rate was calculated by intention-to-treat and per-protocol analysis. RESULTS: Two hundred seventy-nine patients (123 male, 156 female) were eligible for randomization. In per-protocol analysis (n=247), Helicobacter pylori was eradicated with ranitidine bismuth citrate- and lansoprazole-based regimens in 74,6% and 69,2% of cases, respectively (p>0,05). Intention-to-treat analysis (n=279) revealed that eradication rates were 65,1% and 63,6% in ranitidine bismuth citrate and in lansoprazole-based regimens, respectively (p>0,05). Both regimes were well-tolerated, and no serious adverse event was observed during the study. CONCLUSION: Ranitidine bismuth citrate-based regimen is at least as effective and tolerable as the classical proton-pump inhibitor-based regimen, but none of the therapies could achieve the recommendable eradication rate.

Double-liposome-based dual-drug delivery system as vectors for effective management of peptic ulcer.

The aim of the present investigation was to prepare and evaluate a vesicular dual-drug delivery system for effective management of the mucosal ulcer. Inner encapsulating and double liposomes were prepared by the glass-bead and reverse-phase evaporation methods, respectively. The formulation consisted of inner liposomes bearing ranitidine bismuth citrate (RBC) and outer liposomes encapsulating amoxicillin trihydrate (AMOX). The optimized inner liposomes and double liposomes were extensively characterized for vesicle size, morphology, zeta potential, vesicles count, entrapment efficiency, and in vitro drug release. In vitro, the double liposomes demonstrated a sustained release of AMOX and RBC of 93.6 ± 1.9 and 84.1 ± 0.9%, respectively, at the end of 144 hours. Ex vivo studies were conducted on Helicobacter pylori (ATCC26695) bacterial cell lines. Double liposomes showed a more enhanced percent H. pylori growth inhibition than the plain drug combination. Further, in vivo studies illustrated enhanced antisecretory and ulcer-protective activity of double liposomes, as compared to the plain drug combination. Microscopic studies also supported the ulcer-protective action of the formulation. Thus, it may be concluded that double liposomes are instrumental in reducing gastric secretions and targeting ulcer sites with the interception of minimal side effects, thus suggesting their potential in ulcer therapy.

The prototypical ranitidine analog JWS-USC-75-IX improves information processing and cognitive function in animal models.

This study was designed to evaluate further a prototypical ranitidine analog, JWS-USC-75-IX, [(3-[[[2-[[(5-dimethylaminomethyl)-2-furanyl]methyl]thio]ethyl]amino]-4-nitropyridazine, JWS], for neuropharmacologic properties that would theoretically be useful for treating cognitive and noncognitive behavioral symptoms of neuropsychiatric disorders. JWS was previously found to inhibit acetylcholinesterase (AChE) activity, serve as a potent ligand at muscarinic M2 acetylcholine receptors, and elicit positive effects on spatial learning, passive avoidance, and working memory in rodents. In the current study, JWS was evaluated for binding activity at more than 60 neurotransmitter receptors, transporters, and ion channels, as well as for inhibitory activity at AChE and butyrylcholinesterase (BChE). The results indicate that JWS inhibits AChE and BChE at low (micromolar) concentrations and that it is a functional antagonist at M2 receptors (K(B) = 320 nM). JWS was subsequently evaluated orally across additional behavioral assays in rodents (dose range, 0.03-10.0 mg/kg) as well as nonhuman primates (dose range, 0.05-2.0 mg/kg). In rats, JWS improved prepulse inhibition (PPI) of the acoustic startle response in nonimpaired rats and attenuated PPI deficits in three pharmacologic impairment models. JWS also attenuated scopolamine and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801)-related impairments in a spontaneous novel object recognition task and a five-choice serial reaction time task, respectively. In monkeys, JWS elicited dose-dependent improvements of a delayed match-to-sample task as well as an attention-related version of the task where randomly presented (task-relevant) distractors were presented. Thus, JWS (potentially via effects at several drug targets) improves information processing, attention, and memory in animal models and could potentially treat the cognitive and behavioral symptoms of some neuropsychiatric illnesses.

Helicobacter pylori eradication therapy.

Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.

Efficacy of two different Helicobacter pylori eradication regimens in patients with type 2 diabetes and the effect of Helicobacter pylori eradication on dyspeptic symptoms in patients with diabetes: a randomized controlled study.

BACKGROUND: The eradication rate of Helicobacter pylori with a standard triple regimen has been reported as being lower in patients with type 2 diabetes mellitus (DM) than in those without DM. The aim of this study was to evaluate the efficacy and tolerability of 2 different H. pylori eradication regimens in patients with type 2 DM. METHODS: Ninety-eight consecutive type 2 DM and 116 nondiabetic age- and sex-matched patients were enrolled in this study. Patients were randomized to receive either pantoprazole, clarithromycin, and amoxicillin (PCA) for 14 days or ranitidine-bismuth citrate, clarithromycin, and amoxicillin (RCA) for 14 days as the eradication regimen. H. pylori eradication was assessed using C14-urea breath test 6 weeks after the end of therapy. RESULTS: The H. pylori eradication rate with PCA regimen in patients with DM with both intention-to-treat (ITT) and per protocol (PP) analysis was 24/49 (48.9% and 62.9%) and in non-DM patients was 44/58 (75.9% and 86.7%) with ITT and 44/57 (77.2% and 88.2%) with PP analysis (P < 0.05). The H. pylori eradication rates with RCA regimen in patients with DM were 22/49 (45.9% and 59.8%) with ITT and 22/48 (45.8% and 59.9%) with PP analysis and in non-DM patients were 44/58 (75.9% and 86.7%) with ITT and 44/56 (78.6% and 89.3%) with PP analysis. CONCLUSIONS: These data suggest that the eradication rate of H. pylori with PCA or RCA treatment is lower in patients with type 2 diabetes than in nondiabetics and that successful eradication could decrease dyspeptic symptoms.

The efficacy of ranitidine bismuth citrate, amoxicillin and doxycycline or tetracycline regimens as a first line treatment for Helicobacter pylori eradication.

BACKGROUND: The eradication rates of Helicobacter pylori (H. pylori) clearly decreased with standard PPI-based triple therapies. AIM: To assess the efficacy of two different triple therapies consisting of ranitidine bismuth citrate-amoxicillin-doxycycline and ranitidine bismuth citrate-amoxicillin-tetracycline combinations as a first line treatment option. METHODS: One hundred and fifteen consecutive dyspeptic patients in whom H. pylori infection was diagnosed for the first time were enrolled in this study. The patients were randomized into two groups. Group 1 (n=57) was assigned to receive a 14-day triple therapy consisting of ranitidine bismuth citrate 400 mg (b.i.d.), amoxicillin 1 g (b.i.d) and doxycycline 100 mg (b.i.d.). Group 2 (n=58) was assigned to receive a 14-day triple therapy consisting of ranitidine bismuth citrate 400 mg (b.i.d.), amoxicillin 1 g (b.i.d.) and tetracycline 500 mg (q.i.d.). RESULTS: The eradication was achieved in 45.7% (21/46) and 40.8% (20/49) of the patients in group 1 and group 2, according to per protocol analysis. The intention-to-treat eradication rates were 36.8% (21/57) and 34.5% (20/58) in group 1 and group 2, respectively. CONCLUSIONS: Two-week therapy with neither ranitidine bismuth citrate-amoxicillin-doxycycline nor ranitidine bismuth citrate-amoxicillin-tetracycline is adequately effective for H. pylori eradication as a first line therapy.

Effects of ranitidine and its photoderivatives in the aquatic environment.

This study was designed to assess the overall ecotoxicity of ranitidine, a histamine H(2)-receptor antagonist that inhibits stomach acid production. Hence, in addition to ranitidine, its main two photoderivatives, obtained by solar simulator irradiation in water, were investigated. The photoproducts were identified by their physical features. Bioassays were performed on rotifers and microcrustaceans to assess acute and chronic toxicity, while SOS Chromotest and Ames test were utilized to detect the genotoxic potential of the investigated compounds. The results showed that ranitidine did not show any acute toxicity at the highest concentration tested (100 mg/L) for all the organisms utilized in the bioassays. Chronic exposure to these compounds caused inhibition of growth population on rotifers and crustaceans. Genotoxic and mutagenic effects were especially found for one photoproduct suggesting that transformation products, as frequently demonstrated, may show effects higher than the respective parental compound.

Sequential therapy vs. standard triple therapies for Helicobacter pylori infection: a meta-analysis.

BACKGROUND: As standard triple therapies of achieve unsatisfactory eradication of Helicobacter pylori, several alternative regimens have been proposed. OBJECTIVES: To systematically evaluate whether sequential treatment eradicates H. pylori infection better than standard triple therapies and compare the risk of adverse events with these two regimens. METHODS: We searched electronic databases up to February 2008 for studies evaluating the efficacy of the 10-day sequential therapy vs. standard triple regimens for eradication of H. pylori. The pooled risk ratios (RR) and 95% confidence intervals (95% CI) were calculated. RESULTS: We identified 11 randomized trials, including eight full-text manuscripts and three abstracts. Pooled analysis demonstrated clear superiority of the sequential therapy over 7-day triple regimen with an RR of 1.23 (95% CI 1.19-1.27), and over 10-day triple regimen with a RR of 1.16 (95% CI 1.10-1.23). Adverse event rates were similar. For sequential therapy vs. 7-day triple therapies, RR = 0.96, 95% CI 0.70-1.31. CONCLUSIONS: Sequential therapy was associated with a higher eradication rate of H. pylori compared with both 7-day triple regimen and 10-day triple regimen.

Moxifloxacine plus amoxicillin and ranitidine bismuth citrate or esomeprazole triple therapies for Helicobacter pylori infection.

Up to 20% of patients, or even more, will fail to obtain eradication after a standard triple therapy. The aim of this study is to evaluate the efficacy of moxifloxacine-containing regimens in the first-line treatment of Helicobacter pylori. One hundred and twenty H. pylori-positive patients were randomized into four groups to receive one of the following 14-day treatments: ranitidine bismuth citrate (RBC) 400 mg b.d. plus amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (RAC group, n = 30); RBC 400 mg b.d. plus moxifloxacine 400 mg o.d. and amoxicillin 1,000 mg b.d. (RAM group, n = 30); esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus clarithromycin 500 mg b.d. (EAC group, n = 30); and esomeprazole 40 mg b.d. plus amoxicillin 1,000 mg b.d. plus moxifloxacine 400 mg o.d. (EAM group, n = 30). Eradication was assessed by (13)C urea breath test 8 weeks after therapy. Per-protocol and intention-to-treat eradication was achieved in 23 out of 30 patients (76.7%, 95% confidence interval [CI]: 61-92) in the RAC group, in 20 patients (66.7%, 95% CI: 49-84) in the RAM group, in 16 patients in the EAM group (53.3%, 95% CI: 34-71), and in 19 patients in the EAC group (63.3%, 95% CI: 54-72). Mild or moderate side-effects were significantly more common in the EAM group (70%) compared to the RAC (36.6%), RAM (43.3%), and EAC (56.6%) groups (P = 0.03). From our results, we conclude that moxifloxacine-containing triple therapies have neither eradication nor compliance advantages over standard triple therapies. Further studies with new antibiotic associations are needed for the better eradication of H. pylori in developing regions of the world.

Interpretation of the 13C-urea breath test in the choice of second- and third-line eradication of Helicobacter pylori infection.

BACKGROUND: The urea breath test (UBT) is one of the most accurate methods of assessing Helicobacter pylori status. The predictive value of the test is, however, uncertain. This study was a serial, prospective analysis of the change over time of UBT values after first-, second- and third-line treatments of patients with failed eradication therapy. METHODS: One hundred thirty-four duodenal ulcer patients with persisting H. pylori infection after first-line triple therapy were enrolled in a cross-over manner to receive either pantoprazole (40 mg twice daily), amoxicillin (1000 mg twice daily), and clarithromycin (500 mg) or ranitidine bismuth citrate (400 mg twice daily), metronidazole (250 mg twice daily), and clarithromycin (500 mg twice daily) for 7 days. Forty-one patients with failed second-line treatment were randomized to receive third-line quadruple therapies with pantoprazole + amoxicillin and tetracycline (500 mg four times daily) and either nitrofurantoin (100 mg three times daily) or bismuth subsalicylate (120 mg four times daily). Breath tests were performed 6 weeks after therapy. The delta(13)CO(2) values ( per thousand) after primary, secondary, and tertiary treatment were analyzed, and the correlation between pretreatment values and the rate of H. pylori eradication was assessed. RESULTS: In patients with successful second-line treatment, UBT values decreased from 12.4 per thousand [confidence interval (CI), 9.7-15.7)] to 2.8 per thousand (CI, 0.9-2.5) (P=0.001), and in those with persistent infection, they increased from 13.2 per thousand (CI, 7.3-19.1) to 19.2 per thousand (CI, 13.4-25.0) (P=0.03). After a failed quadruple regimen, UBT values increased from 19.3 per thousand (CI, 16.2-22.4) to 25.8 per thousand (CI, 19.8-312.8) (P=0.03). The correlation between the pretreatment UBT values and the rate of eradication was negative for both second- and third-line therapies. CONCLUSIONS: Serial assessment showed that UBT values after successive treatments showed a marked tendency to increase over time in failed cases. The significance of this phenomenon must be further studied. It might indicate increased colonization, ongoing resistance, or urease gene overexpression. Higher pretreatment UBT values were associated with lower (<60%) eradication rates. In these cases, alternative/rescue therapies should be chosen.

Poor efficacy of ranitidine bismuth citrate-based triple therapies for Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori eradication rates have tended to decrease recently possibly related with increasing antibiotic resistance. The present study investigated the efficacy of three different ranitidine bismuth citrate (RBC) based triple regimens in a population with high prevalence of H. pylori. METHODS: 300 consecutive H. pylori positive patients with non-ulcer dyspepsia were randomized into three regimens: (1) RBC 400 mg, amoxicillin 1000 mg and tetracycline 500 mg [RBC-AT], (2) RBC 400 mg, amoxicillin 1000 mg and clarithromycin 500 mg [RBC-AC], (3) RBC 400 mg, metronidazole 500 mg and tetracycline 500 mg [RBC-MT]. Tetracycline was given q.i.d, all other drugs were given b.i.d. for 14 days. Gastroscopy and (14)C-Urea breath test (UBT) were performed before enrollment and UBT only was repeated 6 weeks after the end of treatment. RESULTS: 274 patients completed the protocols. The overall 'intention to treat' and 'per protocol' H. pylori eradication rates in all subjects were 57.6% (95% CI: 52-63) and 63.1% (95% CI: 57-68), respectively. The eradication rates achieved in the groups (RBC-AT, RBC-AC and RBC-MT) were 64.4% (95% CI: 54-74), 66.2% (95% CI: 56-76), and 58.9% (95% CI: 49-68) on 'per protocol' analyses, respectively. There was no difference in eradication rates, compliance and major side effects between the groups. CONCLUSION: The current RBC-based H. pylori eradication therapy is not adequately effective.

Nitrofuran-based regimens for the eradication of Helicobacter pylori infection.

Several aspects of Helicobacter pylori eradication have been meta-analyzed; however, nitrofuran-based therapies constitute an exception. The aim of this study was the systematic review and meta-analysis of the effect of furazolidone- and nitrofurantoin-based regimens in the eradication of infection. Studies evaluating the effects of nitrofurans on H. pylori were identified from Medline, EMBASE, the Cochrane Controlled Trials Register and congress abstracts. The studies were classified into groups based on first-, second- and third-line regimens. The pooled eradication rates and combined odd ratios of the individual studies were calculated and compared with the published meta-analysis. The factors influencing the efficiency of the regimens were also analyzed. Side-effects of nitrofuran-based regimens were also analyzed. The pooled eradication rate of primary proton pump inhibitor-based regimens containing furazolidone was 76.3% (CI 67.8-84.2). The odds ratio for furazolidone-based regimens versus standard triple therapies was 2.34 (CI 0.76-3.92). Ranitidine bismuth citrate + furazolidone-based triple regimens were equally efficient (83.5%, CI 74.0-93.0, P = 0.06 versus triple therapies). Schedules including a H(2) antagonist + furazolidone + one other antibiotic achieved pooled eradication rates of 79.9% (CI 67.8-89.9, P = 0.04). Bismuth-based triple therapies achieved 84.5% (CI 72.6-93.0, P = 0.002). Primary quadruple regimens containing furazolidone were superior to triple therapies (83.4%, CI 69.7-92.3, P = 0.01). Second-line schedules containing furazolidone obtained eradication rates of 76.1% (CI 66.4-85.0, P = 0.28 versus primary regimens). Third-line 'rescue' therapies were efficient in 65.5% of the cases (CI 56.3-75.5, P = 0.0001). Side-effects of the regimens containing furazolidone were more frequent than in standard therapies (P = 0.02). The combined odds ratio of side-effects for furazolidone-based versus standard therapies was 0.74 (CI 0.32-1.98). The duration of treatment, but not the furazolidone dose, influenced the treatment outcome. Primary triple regimens containing furazolidone are slightly less efficient than the standard primary combinations; primary quadruple regimens were more efficient than triple therapies. Furazolidone is also efficient as a component of second-line or rescue therapies.

First-line triple therapy with levofloxacin for Helicobacter pylori eradication.

BACKGROUND: At present, the efficacy of proton pump inhibitor-clarithromycin-amoxicillin regimen is relatively low. AIM: To evaluate the efficacy and tolerability of a first-line triple clarithromycin-free regimen including ranitidine bismuth citrate, levofloxacin and amoxicillin. DESIGN: Prospective study. PATIENTS: Helicobacter pylori-positive patients complaining of dyspeptic symptoms referred for gastroscopy. INTERVENTION: Levofloxacin (500 mg b.d.), amoxicillin (1 g b.d.) and ranitidine bismuth citrate (400 mg b.d.) was prescribed for 10 days. OUTCOME: Eradication was confirmed by a (13)C-urea breath test 8 weeks after therapy. Compliance with therapy was determined by questioning and the recovery of empty envelopes of medications. Incidence of adverse effects was evaluated by means of a specific questionnaire. RESULTS: Sixty-four patients were included (30% peptic ulcer, 70% functional dyspepsia). Almost all (97%) patients took all the medications correctly. Per-protocol and intention-to-treat eradication rates were 88.5% (95% CI =78-95%) and 84.4 (74-91%). Adverse effects were reported in 9.5% of the patients, mainly including diarrhoea (7.9%); none of them were severe. CONCLUSION: This new 10-day levofloxacin-based combination represents an alternative to clarithromycin-based therapy, as it meets the criteria set for regimens used as primary H. pylori treatment: effectiveness (>80%), simplicity (twice-daily dosing and excellent compliance) and safety (low incidence of adverse effects).

Effect of lactoferrin supplementation on the effectiveness and tolerability of a 7-day quadruple therapy after failure of a first attempt to cure Helicobacter pylori infection.

BACKGROUND: Up to 35% of H. pylori-positive patients remain infected after a first eradication attempt. Lactoferrin, a natural anti-bacterial glycoprotein, seems a promising tool in treating H. pylori infection, but it has never been used in second-line treatment. MATERIAL/METHODS: A prospective, randomized study was conducted on 70 consecutive patients with persistent H. pylori infection after failure of the first standard treatment schedule. All patients were randomly treated with ranitidine bismuth citrate (RBC, 400 mg b.d.), esomeprazole (40 mg/day), amoxycillin (1 g t.d), and tinidazole (500 mg b.d.) without (group A) or with (group B) supplementation of bovine lactoferrin (200 mg b.d). One month after conclusion of therapy, endoscopy was performed in those patients for whom the examination was clinically relevant. The remaining patients were checked by 13C-urea breath test. RESULTS: Sixty-seven patients were fully compliant and completed the study (33, i.e. 94.28%, in group A and 34, 97.14%, in group B). One group A patient (2.85%) was excluded for protocol violation and one group B patient (2.85%) was lost to follow-up. H. pylori eradication was obtained in 31/33 (on intention-to-treat: 88.57%, 95%CI: 87-99%) group A patients and in 33/34 (on intention-to-treat: 94.28%, 95%CI: 86-100%) group B patients (p=ns). 16/68 patients (23.53%) experienced side effects (29.41% in group A and 17.64% in group B, p= 0.05). CONCLUSIONS: Lactoferrin supplementation was found effective in reducing side-effect incidence. Moreover, it seems capable of achieving a slight (and not statistically significant) improvement in eradicating H. pylori when used in second-line treatment.

Levofloxacin- vs. ranitidine bismuth citrate-containing therapy after H. pylori treatment failure.

AIM: Ranitidine bismuth citrate and levofloxacin-based regimen may be an alternative to quadruple therapy after Helicobacter pylori eradication failure. Our aim was to compare two 7-day triple second-line regimens containing ranitidine bismuth citrate or levofloxacin. METHODS: Patients in whom a first eradication trial with omeprazole-clarithromycin-amoxicillin had failed were randomized to receive 7-day treatment with: 1, ranitidine bismuth citrate (400 mg b.i.d.), tetracycline (500 mg q.i.d.), and metronidazole (250 mg q.i.d.), or 2, levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.), and omeprazole (20 mg b.i.d.). Cure rates were evaluated by (13)C-urea breath test. RESULTS: One-hundred patients were included: 50 received the ranitidine bismuth citrate regimen, and 50 the levofloxacin one. Groups were comparable in terms of demographic variables. Two percent of the patients (one in each group) did not return for follow up. Compliance was similar in both groups (90% took all the medications correctly). Side-effects (only mild/moderate) in the two groups were also comparable (38% with ranitidine bismuth citrate and 36% with levofloxacin). Per-protocol cure rates were 69% (95% CI = 54-80%) in the ranitidine bismuth citrate group, and 71% (57-82%) in the levofloxacin one. Intention-to-treat cure rates were, respectively, 68% (59-79%) and 68% (59-79%) (nonstatistically significant differences). CONCLUSIONS: Both 7-day ranitidine bismuth citrate- and levofloxacin-containing second-line regimens represent alternatives to quadruple therapy in patients with previous omeprazole-clarithromycin-amoxicillin failure.