Efficacy of reduced-dose regimen of a capsule containing bismuth subcitrate, metronidazole, and tetracycline given with amoxicillin and esomeprazole in the treatment of Helicobacter Pylori infection.
ABSTRACT: It is well known that triple therapy for Helicobacter pylori is losing efficacy worldwide. A regimen containing proton pump inhibitor and multiple-dose capsules of bismuth, metronidazole, and tetracycline has proven efficacy. In addition, a literature review on dosage of previous regimens shows that half-dose clarithromycin-based regimens are equally effective to full-dose regimens. However, the applicability of dose reduction to bismuth-based therapy is unknown. This communication shows that a reduced-dose bismuth-based regimen fails to achieve acceptable eradication rates.
Project description:AIM:To evaluate the efficacy and tolerability of tetracycline vs. high-dose amoxicillin in bismuth-based quadruple therapy for Helicobacter pylori(H. pylori) eradication. METHODS:This randomized, open-label clinical trial included 228 patients with H.pylori infection and duodenal ulcer without a history of H.pylori treatment. Patients were randomly divided into two groups. The amoxicillin group received metronidazole 500mg, bismuth subcitrate 240mg, and amoxicillin 1000mg, all three times a day, plus omeprazole 20 mg twice a day, for 14 days. The tetracycline group received metronidazole 500mg three times a day; bismuth subcitrate240mg and tetracycline HCl 500mg, both four times a day; and omeprazole 20 mg twice a day, for 14 days. Evaluation for compliance and drug-relatedadverse effects were evaluated at the end of two weeks. Eight weeks after the end of treatment, the rate of H.pylori eradication was assessed by the C13urease breath test. RESULTS:There were no significant demographic differences between the two groups. Eradication rate was higher with the amoxicillin-containing regimen than the tetracycline-containing regimen: 105/110 (95.51%; 95% confidence interval, 91.5%-99.3%) vs. 88/105 (83.8%; 95%CI, 76.7%-90.8%) by per-protocol analysis (p = 0.005) and 92.9% (95%CI, 88.1%-97.6%) vs. 76.5% (95%CI, 68.7%-84.2%) by intention-to-treat analysis (ITT, p = 0.001). Adverse effects were significant higher in the tetracycline groupthan in the amoxicillin group (65.2% vs. 43.4%; p = 0.001). CONCLUSION:Bismuth-based quadruple therapy including high-dose amoxicillin and metronidazole achieved an acceptable rate of H.pylori infection eradication with good tolerance in patients with duodenal ulcer. This regimen can overcome treatment resistance in areas with high prevalence of metronidazole and clarithromycin resistance. TRIAL REGISTRATION:The Thai Clinical Trial Registry (TCTR) 20170623004.
Project description:OBJECTIVE:Helicobacter pylori (H. pylori) infection is closely associated with gastric ulcers and gastric adenocarcinomas. We aimed to assess the efficacy and safety of a quadruple regimen with amoxicillin plus berberine vs tetracycline plus furazolidone in rescue therapy for H. pylori eradication. METHODS:We conducted a randomized, open-label, multicenter, noninferiority trial. Patients with previous treatment failures recruited from five centers were randomized (1:1) to receive a regimen with esomeprazole and bismuth plus either berberine and amoxicillin (the BA group) or tetracycline and furazolidone (the TF group) for 14?days. Their H. pylori infection status was confirmed 4-8?weeks after treatment. The primary outcome was the eradication rate. The secondary outcomes included the rates of symptom improvement, compliance, and adverse events. This study was registered at ClinicalTrials.gov (NCT03609892). RESULTS:Altogether 658 participants were consecutively enrolled. An intention-to-treat analysis demonstrated that the two regimens achieved a similar eradication rate (76.3% vs 77.5%; P = 0.781). The per-protocol analysis reached a similar result (81.5% vs 85.0%; P = 0.278). The eradication rate reached in the BA group was greater than the pre-established margin of noninferiority, at -10% (the lower bounds of the 95% CI were?-7.66% and?-9.43%, respectively). The rate of adverse events was lower for the BA group than the TF group (18.5% vs 26.1%, P = 0.024). Rates of compliance and symptom improvement were similar for the two therapies. CONCLUSION:The efficacy of both regimens in rescue treatment for H. pylori eradication was satisfactory, 14-day BA-based quadruple therapy is noninferior to the TF-based therapy.
Project description:BACKGROUND/AIMS: To investigate the effect of the new Helicobacter pylori eradication regimen, ranitidine bismuth citrate (RBC) and clarithromycin (CLAR) dual therapy, on duodenal ulcer healing and absence of ulcer recurrence during 24 weeks follow up (overall success). METHODS: Two hundred and thirty two H pylori positive patients with active duodenal ulcer received four weeks treatment with RBC 400 mg twice daily alone (RBC400) (n = 82), or RBC 400 or 800 mg twice daily co-prescribed with clarithromycin 250 mg four times daily for 14 days, followed by 14 days of RBC 400 mg twice daily alone (RBC400+CLAR and RBC 800+CLAR, respectively, n = 75 for each). RESULTS: The co-prescription regimens gave high H pylori eradication rates determined using two tests (CLOtest and 13C-urea breath test) for the presence of the organism. These rates were 92% and 81% for RBC400+CLAR (n = 62) and RBC800+CLAR (n = 63) respectively, compared with 2% for RBC400 (n = 66) (p < 0.001). With respect to overall success as estimated by life table analysis, RBC400+CLAR (89%) and RBC800+CLAR (87%) were significantly more effective than RBC400 alone (51%) (p < 0.001). All regimens were safe and well tolerated. Trough plasma bismuth concentrations at week 4 were low (treatment medians less than 6.6 ng bismuth/ml). CONCLUSIONS: Ranitidine bismuth citrate is a well tolerated and efficacious ulcer healing drug which, when co-prescribed with clarithromycin, affords effective H pylori eradication therapy and prevents ulcer relapse in most patients with duodenal ulcer.
Project description:The <80 % Helicobacter pylori eradication rate with sequential therapy is unsatisfactory. Modified bismuth quadruple therapy, replacing metronidazole with amoxicillin, could be promising because H. pylori resistance to tetracycline or to amoxicillin is relatively low. A 14-day modified bismuth quadruple protocol as first-line H. pylori treatment was compared with 10-day sequential therapy.In total, 390?H. pylori-infected subjects participated in the randomized clinical trial: 10-day sequential therapy (40 mg pantoprazole plus 1 g amoxicillin twice a day for 5 days, then 40 mg pantoprazole and 500 mg clarithromycin twice a day and 500 mg metronidazole three times a day for 5 days) or 14-day modified bismuth quadruple therapy (40 mg pantoprazole, 600 mg bismuth subcitrate, 1 g tetracycline, and 1 g amoxicillin, twice a day). (13)C-urea breath test, rapid urease testing, or histology was performed to check for eradication.Intention-to-treat (ITT) eradication rates of 10-day sequential and 14-day quadruple therapy were 74.6 % and 68.7 %, respectively, and the per-protocol (PP) rates were 84.2 and 76.5 %, respectively. The eradication rate was higher in the sequential therapy group, but neither the ITT nor the PP analyses had a significant difference (P?=?0.240 and P?=?0.099, respectively). However, the adverse events were significantly lower in the modified bismuth quadruple therapy group than the sequential therapy group (36.9 vs. 47.7 %, P?=?0.040).Ten-day sequential therapy appears to be more effective despite frequent adverse events. However, both 10-day SQT and 14-day PBAT did not reach the excellent eradication rates that exceed 90 %. Additional trials are needed to identify a more satisfactory first-line eradication therapy.ClinicalTrials.gov ( NCT02159976 ); Registration date: 2014-06-03, CRIS ( KCT0001176 ); Registration date: 2014-07-23.
Project description:Background:Helicobacter pylori resistance to amoxicillin remains rare in many regions. Proton pump inhibitor-amoxicillin-containing high dose dual therapy (HDDT) has been proposed to treat H.?pylori infection. We aimed to assess the effectiveness and safety of PPI-amoxicillin HDDT for treatment of H.?pylori infection in comparison with other regimens. Methods:Databases, including PubMed, Embase, and the Cochrane Register of Controlled Trials, were searched to find relevant publications. Randomized controlled trials comparing HDDT with control regimens for H.?pylori eradication in adult patients were included. The primary outcome was eradication rate by intention-to-treat analysis. Adverse events were analyzed as second outcome. Results:A total of 15 trials with 3818 patients qualified for inclusion. The eradication rate of HDDT was neither significantly inferior nor superior to the recommended regimens such as triple therapy, bismuth quadruple therapy, and non-bismuth quadruple therapy [relative risk (RR): 1.00, 95% confidence interval (CI): 0.96-1.05, p?=?0.870]. This finding was robust through subgroup analyses and sensitivity analyses. Trial sequential analysis showed that HDDT was equivalent to control regimens, and further similar trials were unlikely to alter the conclusions of this analysis. The frequency of adverse events was significantly lower in HDDT group (RR: 0.48, 95% CI: 0.37-0.64, p?<?0.001). Conclusion:HDDT was equivalent to recommended first-line or rescue regimens with fewer adverse effects. The evidence from this meta-analysis supports the use of HDDT as first-line or rescue treatment for H.?pylori infection. Trial registration:PROSPERO CRD42019133002.
Project description:This randomized controlled study aimed to evaluate whether adding bismuth to the standard first-line triple therapy could improve the eradication rate of Helicobacter pylori. A total of 162 patients with Helicobacter pylori infection were randomly assigned to either the 7-day triple therapy group (RAK regimen: rabeprazole 20?mg, amoxicillin 1?g, and clarithromycin 500?mg bid; n = 81) or the bismuth plus triple therapy group (n = 81). In the RBAK group, bismuth subcitrate 360?mg twice daily was added to the RAK regimen. A follow-up endoscopy or urea breath test was performed at least 4 weeks after eradication to confirm the treatment efficacy. Comparable compliance and Helicobacter pylori eradication rates were observed in both groups in either intention-to-treat [RAK 72.8% (59/81) versus RBAK 77.8% (63/81); p = 0.47] or per protocol analysis [RAK 74.7% (59/79) versus RBAK 81.8% (63/77); p = 0.26]. Adverse effects were commonly reported (50.6% for both groups) although most of these did not cause cessation of treatment. The resistance rate was 27.2% for metronidazole and 12.3% for clarithromycin. Adding bismuth to the standard 7-day triple therapy did not substantially increase the eradication rate. Further study is needed clarifying whether extending the duration of RBAK regimen to 10-14 days can lead to a better result.
Project description:BACKGROUND:Clarithromycin-containing triple regimen for eradication of Helicobacter pylori is no longer acceptable in Korea due to high clarithromycin resistance. Concomitant therapy or bismuth-containing quadruple therapy is recommended as an alternative regimen. A recent study in Korea has shown that modified quadruple therapy has comparable efficacy and safety to concomitant therapy as a first-line regimen. However, there has been no comparative study of modified quadruple therapy with bismuth-containing quadruple therapy. The aim of this study is to compare the efficacy and safety of modified quadruple therapy with those of bismuth-containing quadruple therapy as a first-line regimen and to present the phenotypic and genotypic antibiotic resistance profile of H pylori. METHODS:This study is an open-label, multicenter, randomized controlled trial. We are recruiting subjects endoscopically diagnosed with H pylori infection from 2 hospitals in Korea. Subjects will be randomly allocated either to modified quadruple therapy (proton-pump inhibitor bid, amoxicillin 1 g bid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid daily) or bismuth-containing quadruple therapy (proton-pump inhibitor bid, tetracycline 500 mg qid, metronidazole 500 mg tid, bismuth subcitrate 300 mg qid daily) for 14 days. The rate of eradication success and adverse events will be checked at least 4 weeks after the treatment. Antibiotic resistance will be established using both a bacterial culture with agar dilutions and DNA sequencing of the clarithromycin resistance point mutations in the 23S rRNA gene of H pylori. CONCLUSION:The results of this study will provide solid evidence for determining the optimal treatment regimen for first-line H pylori eradication in Korea.
Project description:Pattern of gene expression of M. mazei in response to 10 uM bismuth nitrate was analyzed relative to gene expression pattern of M. mazei grown in the presence of 30 uM potassium nitrate (control cultures). Therefore, five pre-cultures of M. mazei was grown to mid-exponential growth-phase. Then, the pre-cultures were divided into aliquotes, one half spiked with bismuth nitrate and the other half with potassium nitrate (control) to match nitrate concentration of the bismuth spike. Samples were propagated for two days. Then, total RNA was isolated and transformed into Cy3 or Cy5 labeled cDNA. Labeled cDNA derived from one culture treated with bismuth and from one control culture, both obtained from the same pre-culture, was hybridized with microarray chips. Hybridized chips were scanned, derived data processed and relative expression levels of orfs from M. mazei in response to bismuth calculated.
Project description:BACKGROUNDS:Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS:In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS:The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS:This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.
Project description:Enrichment cultures were conducted using bismuth subsalicylate as the sole source of carbon and activated sludge as the inoculum. A pure culture was obtained and identified as a Fusarium sp. based on spore morphology and partial sequences of 18S rRNA, translation elongation factor 1-alpha, and beta-tubulin genes. The isolate, named Fusarium sp. strain BI, grew to equivalent densities when using salicylate or bismuth subsalicylate as carbon sources. Bismuth nitrate at concentrations of up to 200 muM did not limit growth of this organism on glucose. The concentration of soluble bismuth in suspensions of bismuth subsalicylate decreased during growth of Fusarium sp. strain BI. Transmission electron microscopy and energy-dispersive spectroscopy revealed that the accumulated bismuth was localized in phosphorus-rich granules distributed in the cytoplasm and vacuoles. Long-chain polyphosphates were extracted from fresh biomass grown on bismuth subsalicylate, and inductively coupled plasma optical emission spectrometry showed that these fractions also contained high concentrations of bismuth. Enzyme activity assays of crude extracts of Fusarium sp. strain BI showed that salicylate hydroxylase and catechol 1,2-dioxygenase were induced during growth on salicylate, indicating that this organism degrades salicylate by conversion of salicylate to catechol, followed by ortho cleavage of the aromatic ring. Catechol 2,3-dioxygenase activity was not detected. Fusarium sp. strain BI grew with several other aromatic acids as carbon sources: benzoate, 3-hydroxybenzoate, 4-hydroxybenzoate, gentisate, d-mandelate, l-phenylalanine, l-tyrosine, phenylacetate, 3-hydroxyphenylacetate, 4-hydroxyphenylacetate, and phenylpropionate.