scholarly journals Comparing the Effect of Two Low-dose and High-dose Four-drug Regimens of Furazolidone in Eradicating Helicobacter Pylori

2021 ◽  
Vol 13 (2) ◽  
pp. 131-138
Author(s):  
Mohammad Reza Seyedmajidi ◽  
Seyed Ashkan Hosseini ◽  
Jamshid Vafaeimanesh

BACKGROUND Antibiotic resistance is a major cause of Helicobacter pylori (H. pylori) treatment failures. The increased resistance to clarithromycin and metronidazole has reduced the ability of this therapeutic regimen and prompted researchers to look for other drugs. One of the antibiotics of interest in this regard is furazolidone because of its low drug resistance. The aim of this study is compare two-drug regimens including low-dose and high-dose furazolidone in the treatment of H. pylori. METHODS This study is a clinical trial in which the studied subjects were categorized into two groups. The first group underwent treatment with amoxicillin 1000 mg-BD, furazolidone 100 mg-BD, omeprazole 20 mg-BD, and bismuth subcitrate 240 mg-BD for two weeks (low-dose OFAB). The second group received furazolidone 200 mg-BD (high-dose OFAB). Then eight weeks after completion of the treatment, they were examined in terms of eradication via the UBT test. RESULTS 85 participants completed the study in each group. The response to treatment was 76% and 83% in the low and high-dose groups, respectively, based on intention to treat analysis. Based on per protocol analysis the response to treatment was 78% and 84%, respectively, if excluded patients had completed their protocol and had response to treatment, and 72% and 79%, respectively, if excluded patients had completed their protocol and did not have response to treatment (p = 0.298). In the low-dose and high-dose groups, 16.5% and 24.7% of the participants suffered the complications of treatment with furazolidone (p = 0.18), respectively. Three patients in the high-dose group and one in the low-dose group did not complete the treatment because of the medication’s bad taste (p = 0.03). CONCLUSION Low doses of furazolidone had a comparable therapeutic effect compared with high doses, but patients experienced significantly lower levels of bad taste, which was a major cause of reluctance to continue treatment. Therefore, we think four-drug low-dose furazolidone treatment is a good choice in eradicating H. pylori.

2020 ◽  
Author(s):  
Fariborz Mansour-Ghanaei ◽  
Behnam Masihypour ◽  
Mohammad Fathalipour ◽  
Soheil Hassanipour ◽  
Homayoon Sokhanvar ◽  
...  

Abstract BackgroundThe incidence of microbial resistance is increasing, and new rescue regimens are needed in order to treat Helicobacter pylori (H. pylori) infection. To evaluate the efficacy, safety, and tolerability of levofloxacin based quadruple therapies in the eradication of H. pylori.MethodsIn a randomized, double-blind clinical trial, 220 patients with dyspepsia and H. pylori infection were randomly assigned to receive either bismuth subcitrate 240 mg, pantoprazole 20 mg, amoxicillin 1000 mg twice a day, and levofloxacin 500 mg daily for seven days (BPAL-7), or ten days (BPAL-10). The eradication of H. pylori was evaluated two months after the end of treatment, and adverse drug reactions (ADRs) were assessed during the intervention.ResultsAccording to intention-to-treat and per-protocol, the eradication rate was significantly lower in the BPAL-7 regimen 49.1% (95% CI: 39.3–57.8) and 47.6% (95% CI: 39.7–58.4), respectively compared to the BPAL- 10 regimen 62.7% (95% CI: 53.6–72.8) and 62.4% (95% CI: 55.1–72.8), respectively. The incidence of ADRs was not statistically significant between BPAL-7 (33.6%) and BPAL-10 (36.7%) groups.ConclusionAlthough the ADRs were negligible in both groups, these regimens could not be an ideal alternative therapy for H. pylori because of low eradication rates compared to standard regimens.Trial registration: The study reviewed and approved by the Iranian Registry of Clinical Trials (IRCT201406141155N19). This trial was retrospectively registered on July 10, 2015.


2021 ◽  
Author(s):  
Fariborz Mansour-Ghanaei ◽  
Behnam Masihypour ◽  
Mohammad Fathalipour ◽  
Soheil Hassanipour ◽  
Homayoon Sokhanvar ◽  
...  

Abstract The incidence of microbial resistance is increasing, and new rescue regimens are needed in order to treat Helicobacter pylori (H. pylori) infection. To evaluate the efficacy, safety, and tolerability of levofloxacin based quadruple therapies in the eradication of H. pylori. In a randomized, double-blind clinical trial, 220 patients with dyspepsia and H. pylori infection were randomly assigned to receive either bismuth subcitrate 240 mg, pantoprazole 20 mg, amoxicillin 1000 mg twice a day, and levofloxacin 500 mg daily for seven days (BPAL-7), or ten days (BPAL-10). The eradication of H. pylori was evaluated two months after the end of treatment, and adverse drug reactions (ADRs) were assessed during the intervention. According to intention-to-treat and per-protocol, the eradication rate was significantly lower in the BPAL-7 regimen 49.1 % (95 % CI: 39.3-57.8) and 47.6 % (95 % CI: 39.7-58.4), respectively compared to the BPAL- 10 regimen 62.7 % (95 % CI: 53.6-72.8) and 62.4 % (95 % CI: 55.1-72.8), respectively. The incidence of ADRs was not statistically significant between BPAL-7 (33.6 %) and BPAL-10 (36.7 %) groups. Although the ADRs were negligible in both groups, these regimens could not be an ideal alternative therapy for H. pylori because of low eradication rates compared to standard regimens.Trial registration: The study reviewed and approved by the Iranian Registry of Clinical Trials (IRCT201406141155N19).


Gut ◽  
1998 ◽  
Vol 42 (2) ◽  
pp. 166-169 ◽  
Author(s):  
R W M van der Hulst ◽  
A van der Ende ◽  
A Homan ◽  
P Roorda ◽  
J Dankert ◽  
...  

Background—Metronidazole-containing eradication therapies are less effective for metronidazole resistantHelicobacter pylori. Although early data suggested improvement of the efficacy of bismuth triple therapy after the addition of acid suppressives, these findings were based on studies with small numbers of patients, incomplete post-eradication follow up, or omission of pretreatment susceptibility testing.Aims—To study the efficacy of quadruple therapy in the Amsterdam area, where the efficacy of bismuth triple therapy has been proved to be affected by metronidazole resistance.Patients and methods—Eighty two consecutive dyspeptic H pylori positive patients with either metronidazole susceptible (group I) or metronidazole resistant H pylori strains (group II) received quadruple therapy for one week: omeprazole 20 mg twice daily; colloidal bismuth subcitrate 120 mg four times a day; tetracycline 500 mg four times a day; metronidazole 500 mg three times a day. Susceptibility to metronidazole was determined by the E-test.Results—Intention to treat analysis showed thatH pylori infection had been cured in 42/43 patients (98%) in group I and 32/39 patients (82%) in group II (p = 0.02).Conclusion—The efficacy of quadruple therapy is significantly impaired in patients infected with metronidazole resistant H pylori. Therefore a non-metronidazole-containing regimen should preferably be used in areas known to have a high prevalence of pretreatment metronidazole resistance.


2019 ◽  
Vol 91 (8) ◽  
pp. 34-40 ◽  
Author(s):  
N V Bakulina ◽  
I V Maev ◽  
I V Savilova ◽  
I G Bakulin ◽  
T A Il'chishina ◽  
...  

Aim. To evaluate an association of genetic polymorphisms CYP2C19, MDR1, and IL-1β on the eradication rate by 10-day modified therapy in patients with H. pylori - associated diseases. Materials and methods. In this study was conducted a prospective, randomized trial, included 89 patients with H. pylori - associated diseases. They were divided into 2 groups depending on therapy: clarithromycin 500 mg, b.i.d., amoxicillin 1000 mg, b.i.d., bismuth subcitrate 240 mg, b.i.d. rabeprazole 20 mg or 40 mg, b.i.d. for 10 days. All subjects underwent pharmacogenetic testing of CYP2C19, MDR1, and IL-1β. Results and discussion. Per - protocol (PP) eradication rates in group with rabeprazole 40 mg were 97.6% (41/42; 95% CI 87.7-99.6), in group with rabeprazole 20 mg were 82.1% (32/39; 95% CI 67.3-91.0). Intention - to - treat analysis in group with rabeprazole 40 mg eradication rates were 89.1% (41/46; 95% CI 77.0-95.3), in group with standard dose rabeprazole - 74.4% (32/43; 95% CI 59.8-85.1). No significant differences in eradication rates between the groups of ultrarapid, rapid, normal and intermediate CYP2C19 metabolizers (PP: 93.5%/90.3%/84.6% respectively; χ2=0.87, p=0.65). Eradication rates in group with IL-1β CC genotype there was no difference among the IL-1β CT and TT genotype groups (PP: 92.9%/85.7%/94.7% respectively; χ2=1.34; p=0.51). The cure rate among MDR1 TT genotype was significantly lower than among subjects in the MDR1 CC/CT genotype groups (PP: 76.2% vs 96.3%: χ2=5.04; p=0.025; OR=8.13). Conclusion. Ten - day modified triple therapy with high dose rabeprazole significantly high eradication rates in patients with H. pylori - associated diseases. Independent factor for treatment failure is MDR1 CC/CT genotype status.


1984 ◽  
Vol 52 (03) ◽  
pp. 276-280 ◽  
Author(s):  
Sam Schulman ◽  
Dieter Lockner ◽  
Kurt Bergström ◽  
Margareta Blombäck

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.


2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Takahashi ◽  
K Tsuchida ◽  
Y Sato ◽  
S Iimuro ◽  
K Kario ◽  
...  

Abstract Background/Introduction The REAL-CAD study identified that aggressive lipid lowering with high-dose statin reduced cardiovascular events also in Japanese patients with coronary artery disease (CAD). However, data from the SPARCL trial found that the benefits of high-dose atorvastatin treatment were partially offset by an increase in haemorrhagic stroke (HS). Although meta-analysis showed statin does not increase HS in Western countries, the evidence about the relation between statin and HS in Asian countries is still conflicting. In addition, the CREDO-Kyoto score is one of the prediction scorings for bleeding after coronary revascularization and might be a useful tool for the prediction of HS in this cohort. Recognizing the risk of HS and predicting of HS in the Asian cohort is clinically important. Purpose This study examined the factors associated with HS using the REAL-CAD cohort. Furthermore, we evaluated the performance of the CREDO-Kyoto bleeding risk score to predict HS in this cohort. We also performed the corresponding analysis of ischaemic stroke for reference purposes. Methods We sub-analysed the REAL-CAD study, prospective, multicentre, randomized, open-label, blinded endpoint study, in which 13,054 Japanese patients with stable CAD were randomized to high-dose (4 mg/day) or low-dose (1 mg/day) pitavastatin. Associations for stroke were determined using competing risk models: the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of haemorrhagic and ischaemic stroke in REAL-CAD trial. Patients were categorized to low (score 0), moderate (score 1–2), and high (score&gt;3) according to CREDO-Kyoto bleeding score for predicting of HS. Results The HS events in high-dose group tended to be higher than low-dose group (4mg vs. 1mg: 43 (0.7%) vs. 30 (0.5%)). The associated factors of HS on univariate analysis were non-prior myocardial (hazard ratio (HR): 0.62, 95% CI: 0.39–0.99) and non-prior cerebral (HR: 0.25, 95% CI: 0.09–0.70) infarction, atrial fibrillation (HR: 2.4, 95% CI: 1.2–4.7), prior HS (HR: 4.2, 95% CI: 1.5–11.8), anaemia (HR: 2.4, 95% CI: 1.4–4.1), and non-statins use before run-in period (HR: 0.52, 95% CI: 0.28–0.99). High-dose pitavastatin was not a correlate with HS. The multivariate analysis revealed anaemia might have a relation with HS (HR: 4.3, 95% CI: 0.90–20.6). The number of HS was the highest in the high CREDO-Kyoto bleeding score group (Figure 1, HR: 2.4, 95% CI: 1.3–4.6), whereas there was no significant difference in the number of HS between the moderate- and low-risk groups (HR: 1.4, 95% CI: 0.84–2.3). Conclusions High-dose pitavastatin was not associated with the incidence of HS in this large Japanese cohort with stable CAD. High CREDO-Kyoto bleeding score was associated with HS as compared with low or moderate scores, even each of the variables consisting of CREDO-Kyoto score was not associated with HS. Figure 1 Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naomi S. Sta Maria ◽  
Leslie A. Khawli ◽  
Vyshnavi Pachipulusu ◽  
Sharon W. Lin ◽  
Long Zheng ◽  
...  

AbstractQuantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3–5 h and then migrate to the liver and spleen for up to 2–3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1427
Author(s):  
Junhui Zhang ◽  
Fengqin Feng ◽  
Minjie Zhao

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg−1) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1β) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.


2021 ◽  
Vol 35 ◽  
pp. 205873842110303
Author(s):  
Wenwen Gao ◽  
Xiang Zhang ◽  
Yanhui Yin ◽  
Shuwen Yu ◽  
Lu Wang

The evidence on whether high-dose new generation proton pump inhibitors (PPIs) including rabeprazole and esomeprazole achieve a higher eradication rate of Helicobacter pylori has not been assessed. The primary comparison was eradication and adverse events (AEs) rate of standard (esomeprazole 20 mg bid, rabeprazole 10 mg bid) versus high-dose (esomeprazole 40 mg bid, rabeprazole 20 mg bid) PPIs. Sub-analyses were performed to evaluate the eradication rate between Asians and Caucasians, clarithromycin-resistance (CAM-R) strains, and clarithromycin-sensitivity (CAM-S) strains of different dose PPIs. We conducted a literature search for randomized controlled trials comparing high-with standard-dose esomeprazole and rabeprazole for H. pylori eradication and AEs. A total of 12 trials with 2237 patients were included. The eradication rate of high-dose PPIs was not significantly superior to standard-dose PPIs regimens: 85.3% versus 84.2%, OR 1.09 (0.86–1.37), P = 0.47. The high dose induced more AEs than those of the standard dose, but didn’t reach statistical significance (OR 1.25, 95% CI: 0.99–1.56, P = 0.06). Subgroup analysis showed that the difference in eradication rate of PPIs between high- and standard-dose groups were not statistically significant both in Asians (OR 0.99, 95% CI 0.75–1.32, P = 0.97) and Caucasians (OR 1.27, 95% CI 0.84–1.92, P = 0.26). Furthermore, there were similar eradication rates in CAM-S (OR 1.2; 95% CI 0.58–2.5; P = 0.63) and CAM-R strains (OR 1.08; 95% CI 0.45–2.56; P = 0.87) between the standard-and high-dose groups. High and standard dosages of new generation of the PPIs showed similar H. pylori eradication rates and AEs as well as between Asian versus Caucasian populations, with or without clarithromycin-resistance. However, further studies are needed to confirm.


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