Efficacy and safety of a 14-day modified concomitant therapy for refractory Helicobacter pylori infection: a pilot study.

BACKGROUND AND AIM: After three treatment failures, Helicobacter pylori infection is deemed refractory as antibiotic treatment options become significantly limited. This study evaluated the efficacy and safety of a 14-day modified concomitant therapy for managing refractory H. pylori infection. METHODS: Patients who had failed to respond to three or more rounds of H. pylori therapies were recruited for this study. They received a 14-day modified concomitant therapy, including esomeprazole 40 mg, amoxicillin 1000 mg, and furazolidone 100 mg twice daily and tetracycline 500 mg four times daily. Demographic data, adverse events, and patient compliance were recorded. The presence of H. pylori was reevaluated 6 weeks following treatment. Eradication rate was assessed as the primary outcome. RESULTS: Overall, 59 participants received the 14-day modified concomitant therapy. In the intention-to-treat and per-protocol analyses, the eradication rate was 84.7% (50/59) and 89.3% (50/56), respectively. H. pylori was successfully isolated from 75.0% (12/16) of patients. The resistance rate of H. pylori to metronidazole, levofloxacin, and clarithromycin was 91.7% (11/12), 58.3% (7/12), and 50.0% (6/12), respectively. Resistance to amoxicillin, furazolidone, or tetracycline was not observed. The frequency of adverse events was 35.6% (21/59), with no serious adverse events reported. CONCLUSION: The 14-day modified concomitant therapy appears to be appropriate for refractory H. pylori infection and is particularly promising for the Chinese population. A randomized controlled trial is warranted to verify its efficacy, especially in the current environment of increasing antibiotic resistance.

[Effectiveness of empirical Helicobacter pylori eradication therapy with furazolidone in Russia: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)].

BACKGROUND: First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. MATERIALS AND METHODS: Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. RESULTS: Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days - in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. CONCLUSION: Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.

Clarithromycin versus furazolidone for naïve Helicobacter pylori infected patients in a high clarithromycin resistance area.

BACKGROUND AND AIM: The increase in antibiotic resistance makes the eradication of Helicobacter pylori more difficult. Considering the limitations of the application of susceptibility-guided therapy, it is important to find an effective empirical regimen. The aim of the study is to compare the efficacy, safety, and cost-effectiveness of clarithromycin-based bismuth-containing quadruple therapy (C-BQT) and furazolidone-based bismuth-containing quadruple therapy (F-BQT) in naïve H. pylori positive patients. METHODS: This was an open-label, randomized controlled, crossover trial. The trial comprised two phases. In C-F group, patients received C-BQT in the first phase; those who were still positive for H. pylori infection after the first phase entered the second phase to receive F-BQT as rescue treatment. In F-C group, patients were treated with F-BQT firstly and rescued with C-BQT. RESULTS: As first-line treatments, the eradication rates of C-BQT and F-BQT were 89.7% (157/175) and 92.0% (161/175) (P = 0.458) in intention-to-treat analysis and 93.4% (156/167) and 95.8% (161/168) (P = 0.327) in per-protocol analysis, respectively. The cumulative eradication rates of the C-F group and the F-C group were both 94.3% in intention-to-treat analysis (P = 1.000). Cost-effectiveness indexes of F-BQT and C-BQT were 0.54 and 1.24 in first-line treatments. Frequencies of adverse events in F-BQT and C-BQT had no differences (36.0% in C-BQT vs 32.6% in F-BQT, P = 0.499). CONCLUSIONS: Furazolidone-based bismuth-containing quadruple therapy should be preferred for its excellent cost-effectiveness and acceptable safety.

Curcumin Ameliorates Furazolidone-Induced DNA Damage and Apoptosis in Human Hepatocyte L02 Cells by Inhibiting ROS Production and Mitochondrial Pathway.

Furazolidone (FZD), a synthetic nitrofuran derivative, has been widely used as an antibacterial and antiprotozoal agent. Recently, the potential toxicity of FZD has raised concerns, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on FZD-induced cytotoxicity and the underlying mechanism in human hepatocyte L02 cells. The results showed that curcumin pre-treatment significantly ameliorated FZD-induced oxidative stress, characterized by decreased reactive oxygen species (ROS) and malondialdehyde formation, and increased superoxide dismutase, catalase activities and glutathione contents. In addition, curcumin pre-treatment significantly ameliorated the loss of mitochondrial membrane potential, the activations of caspase-9 and -3, and apoptosis caused by FZD. Alkaline comet assay showed that curcumin markedly reduced FZD-induced DNA damage in a dose-dependent manner. Curcumin pre-treatment consistently and markedly down-regulated the mRNA expression levels of p53, Bax, caspase-9 and -3 and up-regulated the mRNA expression level of Bcl-2. Taken together, these results reveal that curcumin protects against FZD-induced DNA damage and apoptosis by inhibiting oxidative stress and mitochondrial pathway. Our study indicated that curcumin may be a promising combiner with FZD to reduce FZD-related toxicity in clinical applications.

Tetracycline- and furazolidone-containing quadruple regimen as rescue treatment for Helicobacter pylori infection: a single center retrospective study.

BACKGROUND AND OBJECTIVE: Eradication rate of Helicobacter pylori decreases worldwide, while antibiotics resistance rates of H. pylori increase rapidly in recent years. In most cases, H. pylori would be resistant to clarithromycin, metronidazole, and quinolone if these antibiotics had been used as component of eradication regimen. H. pylori strains resistant to both tetracycline and furazolidone are rare. The aim of our study was to evaluate efficacy and side effects of tetracycline- and furazolidone-containing quadruple regimen as rescue treatment. METHODS: Patients with H. pylori infection given RTFB (rabeprazole 20 mg b.i.d. + tetracycline 750 mg b.i.d. +furazolidone 100 mg b.i.d. + colloidal bismuth subcitrate 200 mg b.i.d.) regimen for 14 days as rescue treatment were enrolled in this retrospective study. Eradication status was evaluated by (13) C-urea breath test, and side effects were collected. RESULTS: One hundred and nine patients were enrolled. The intention-to-treat eradication rate was 91.74% (100 of 109) and 95.24% (100 of 105) per protocol analysis. Side effects including fever, palpitation, and skin rash occurred in 35 patients. CONCLUSIONS: The 14-day tetracycline- and furazolidone-containing quadruple regimen can achieve a relatively high eradication rate as rescue treatment. Some side effects including fever may occur during the treatment.

[Efficacy and safety of 14-day amoxicillin and furazolidone-based quadruple rescue regimen for eradication of Helicobacter pylori: a retrospective study].

OBJECTIVE: To evaluate the efficacy, compliance and adverse effects of 14-day amoxicillin and furazolidone-based quadruple regimen as rescue treatment for Helicobacter pylori (H.pylori) infection. METHODS: A total of 228 patients positive for H.pylori with previous failed treatment at least once were enrolled into this retrospective study. There were 71 males and 157 females, aged (50 ± 13) years. A 14-day quadruple regimen was administered along with furazolidone, amoxicillin and bismuth citrate in combination with proton pump inhibitors. Adverse effects were recorded at the end of treatment.H.pylori status was assessed by (13)C-urea breath test at 4 weeks after treatment. RESULTS: Among them, 206 patients completed treatment. The H.pylori eradication rates were 91.96% (206/224) and 90.35% (206/228) according to per-protocol (PP) and intention-to-treat (ITT) analyses respectively. Mild and moderate adverse effects such as dizziness, nausea and diarrhea occurred in 43 patients (18.86%). Four of them had to terminate their treatment due to rash, dizziness and headache respectively. CONCLUSIONS: The 14-day quadruple therapy with furazolidone, amoxicillin, bismuth citrate and proton pump inhibitors may be an effective regimen for rescue treatment because of its relatively high eradication rate (>90%). The patients should be watched closely during the treatment since the adverse effects of this regimen happen frequently. Treatment is stopped in events of skin rash, fever or other serious adverse effects.Vitamins B1 and B6 can relieve some discomforts.

Association of a probiotic to a Helicobacter pylori eradication regimen does not increase efficacy or decreases the adverse effects of the treatment: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: The treatment for the eradication of Helicobacter pylori (H. pylori) is complex; full effectiveness is rarely achieved and it has many adverse effects. In developing countries, increased resistance to antibiotics and its cost make eradication more difficult. Probiotics can reduce adverse effects and improve the infection treatment efficacy.If the first-line therapy fails a second-line treatment using tetracycline, furazolidone and proton-pump inhibitors has been effective and low cost in Brazil; however it implies in a lot of adverse effects. The aim of this study was to minimize the adverse effects and increase the eradication rate applying the association of a probiotic compound to second-line therapy regimen. METHODS: Patients with peptic ulcer or functional dyspepsia infected by H. pylori were randomized to treatment with the furazolidone, tetracycline and lansoprazole regimen, twice a day for 7 days. In a double-blind study, patients received placebo or a probiotic compound (Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium bifidum and Streptococcus faecium) in capsules, twice a day for 30 days. A symptom questionnaire was administered in day zero, after completion of antibiotic therapy, after the probiotic use and eight weeks after the end of the treatment. Upper digestive endoscopy, histological assessment, rapid urease test and breath test were performed before and eight weeks after eradication treatment. RESULTS: One hundred and seven patients were enrolled: 21 men with active probiotic and 19 with placebo plus 34 women with active probiotic and 33 with placebo comprising a total of 55 patients with active probiotic and 52 with placebo. Fifty-one patients had peptic ulcer and 56 were diagnosed as functional dyspepsia. The per-protocol eradication rate with active probiotic was 89.8% and with placebo, 85.1% (p=0.49); per intention to treat, 81.8% and 79.6%, respectively (p=0.53). The rate of adverse effects at 7 days with the active probiotic was 59.3% and 71.2% with placebo (p=0.20). At 30 days, it was 44.9% and 60.4%, respectively (p=0.08). CONCLUSIONS: The use of this probiotic compound compared to placebo in the proposed regimen in Brazilian patients with peptic ulcer or functional dyspepsia showed no significant difference in efficacy or adverse effects. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04714018.

Efficacy and safety of modified tetracycline dosing in a quadruple therapy for Helicobacter pylori: A retrospective single center study.

BACKGROUND: Although highly effective as a component of Helicobacter pylori (H. pylori) treatment regimen, tetracycline is associated with a high incidence of medication-related adverse events. Modified dosing of tetracycline as part of quadruple therapy may improve safety while providing comparable eradication rates. AIM: To evaluate the efficacy and safety of modified dosing of tetracycline in patients receiving tetracycline and furazolidone-containing quadruple therapy in patients with H. pylori infection. METHODS: Consecutive patients (10/2020-12/2021) who received tetracycline and furazolidone quadruple therapy for H. pylori infection at Sir Run Run Shaw Hospital were identified. All patients received tetracycline, furazolidone, proton pump inhibitor, and bismuth for 14 d as primary or rescue therapy. Modified tetracycline dose group received tetracycline 500 mg twice daily while standard group received 750 mg twice daily or 500 mg three times daily. RESULTS: Three hundred and ninety-four patients [mean age = 46.3 ± 13.9, male = 137 (34.8%), and 309 (78.4%) primary therapy] completed tetracycline and furazolidone quadruple therapy for H. pylori infection including those who received modified tetracycline dose in 157 and standard doses in 118 (750 mg twice daily) and 119 (500 mg three times daily). Eradication rates in the modified tetracycline dose group were 92.40% and in the standard groups, eradication rates were 93.20% for 750 mg twice daily group and 92.43% for 500 mg three times daily group, respectively, without statistical difference (P = 0.959). The incidence of adverse events was lower in the modified tetracycline dose (15.3% vs 32.3% and 29.4%; P = 0.002) compared to the standard dose group. CONCLUSION: In a real-world experience, modified tetracycline dosing as part of tetracycline and furazolidone quadruple therapy for 14 d demonstrated high efficacy, comparable to standard tetracycline dose regimens, with a favorable safety profile.

The eradicating Helicobacter pylori infection in duodenal ulcer patients by three short-term triple therapies in China: a multicenter clinical comparative study.

BACKGROUND/AIMS: This study aimed to compare the 7d triple therapy with 3d and 5d triple therapies, to observe the effect of eradicating Helicobacter pylori (Hp) on treating duodenal ulcers. METHODOLOGY: One hundred and sixteen patients who were confirmed duodenal ulcer active period and Hp positive were enrolled in the study. All the patients were divided into three groups: 3d group (n=39), 5d group (n=37) and 7d control group (n=40). All three groups were provided triple therapy first: rabeprazole, 10mg + furazolidone, 100mg + clarithromycin 250mg, twice a day for three days, five days and seven days, respectively. Then rabeprazole 10mg was provided once a day. Following the treatment, 13C urea breath test was performed to observe the Hp eradication rate. The symptoms of patients such as epigastralgia, burning pain and acidity were evaluated. RESULTS: The Hp eradication rate was: 3d group 76% (28/37), 5d 89% (31/35) and 7d 91% (32/35). There was no significant difference between 5d and 7d group (p>0.05). But the rate of groups 5d and 7d was significantly higher than group 3d (p<0.05). All the three groups showed an improvement in symptoms such as epigastralgia, burning pain and acidity. CONCLUSIONS: All three therapy schemes could alleviate symptoms of duodenal ulcer patients efficiently. But as far as eradicating Hp concerned, 5d and 7d therapies were better than 3d.

Risk factors of furazolidone-associated fever.

BACKGROUND: Furazolidone is a synthetic nitrofuran with a broad spectrum of antimicrobial action and has been widely used in the treatment of Helicobacter pylori (H. pylori) infection. However, its safety profile has not been clarified. Moreover, the drug fever associated with its use is frequently misdiagnosed. The aim of this study was to explore the risk factors of furazolidone-associated fever to increase awareness and stimulate further research on this topic. METHODS: This was a retrospective case-control study of patients referred to a specialist clinic for furazolidone-containing quadruple regimens for H. pylori infection at a tertiary care hospital located in Eastern China between July 2018 and September 2018. We evaluated adult patients who received furazolidone treatment for Helicobacter pylori infection. The exclusion criteria were as follows: (1) patients were pregnant or breastfeeding; (2) patients received furazolidone treatment not for Helicobacter pylori infection; (3) patients had taken antibiotics or any acid suppressant or non-steroidal anti-inflammatory drug in the last 4 weeks; (4) patients had chronic hepatic, renal, or pulmonary disease. Pertinent information was retrieved from medical records and telephone follow-up. All statistical analysis was performed in SPSS version 22.0. RESULTS: A total of 1499 patients received furazolidone and met the overall inclusion criterion. Of these 1499 patients, 27 (1.80%) developed drug fever. The mean time between initiation of furazolidone and the onset of fever is 11.00 ± 1.84 days, and the median peak fever was 38.87 ± 0.57°C. We found no differences in age and past drug allergy between the non-fever and fever groups. Through multiple logistic regression analysis, we found two variables as independent risk factors for furazolidone-associated fever, including gender (OR, 3.16; 95% CI, 1.26-7.91; P = 0.014) and clarithromycin (OR, 4.83; 95% CI, 2.17-10.79; P<0.001). CONCLUSIONS: This retrospective cohort study identified two risk factors for furazolidone-associated fever, which were female and clarithromycin. We also analyzed the characteristics of drug fever during anti-Helicobacter pylori therapy. However, the underlying mechanisms are uncertain and require further research.

Quadruple therapy with medications containing either rufloxacin or furazolidone as a rescue regimen in the treatment of Helicobacter pylori-infected dyspepsia patients: a randomized pilot study.

BACKGROUND: The eradication rates of first-line treatment for Helicobacter pylori infection are not satisfactory. Various regimens including quadruple therapies have been recommended as rescue therapies after the first H. pylori eradication attempt failed. AIMS: To compare the efficacy and safety between quadruple therapies with medications containing either rufloxacin or levofloxacin in the Chinese nonulcer dyspepsia patients infected with H. pylori. METHODS: One hundred and thirty-eight patients after an unsuccessful 10-day standard triple therapy were enrolled in this study. They were randomized to receive a 14-day quadruple therapy with pantoprazole, bismuth citrate, and furazolidone in combination with either rufloxacin (Group Ruf, n=70) or levofloxacin (Group Lev, n=68). The H. pylori eradication was evaluated by (13) C-urea breath test 4 and 12 weeks after therapy was completed. RESULTS: One hundred and twenty-seven patients (65 in Group Ruf and 62 in Group Lev) completed the study. The H. pylori eradication rates in Group Ruf were 81.4% for intention-to-treat (ITT) analysis and 87.7% for per-protocol (PP) analysis. The rates were statistically significantly higher than those in Group Lev (66.2% and 72.6%) (p<0.05). There were no severe adverse effects found in these two groups. CONCLUSIONS: Fourteen-day quadruple therapy with a combination of proton-pump inhibitor, bismuth citrate, furazolidone, and rufloxacin is considered an effective and safe rescue therapy for H. pylori eradication after failure of standard triple treatment.

[Rifaximin in combined treatment of the Helicobacter pylori infection in childhood].

AIM: To provide a pilot study of empiric rifaximin, bismuth subcitrate, furazolidone/nifuratel triple therapy for H. pylori gastritis in childhood. MATERIALS AND METHODS: Forty one pediatric outpatients (27 females, mean age 14.5 +/- 1.4 ys) with H. pylori-associated chronic gastritis who underwent endoscopy for dyspeptic symptoms received the combination of bismuth subcitrate (8/mg/kg/day, q. d. s.) for 14 days, rifaximin (800 mg/day) for 10 days and furazolidone (10 mg/kg/day, q. d. s.) or nifuratel (15 mg/kg/two times daily) for 10 days. H. pylori status was determined before the treatment by modified Giemsa staining/urease test and after the treatment (in 4-6 weeks) by ammonia breath test. RESULTS: H. pylori was eradicated in 35 children (85.4%; 95% CI: 75.4-96.4 ITT and PP tests). There were no serious adverse reactions and were no withdrawals due to any side effects. CONCLUSION: The combination of rifaximin, bismuth subcitrate and furazolidone/nifuratel was an effective and tolerable regimen for initial H. pylori eradication.

Two Different 1-Week Quadruple Therapies Given Back-to-Back Consecutive Therapy for Difficult-to-Treat Helicobacter pylori Infection: A Pilot Study.

INTRODUCTION: We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection. METHODS: Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed. RESULTS: Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3-7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin). DISCUSSION: Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection.

Sequential metronidazole-furazolidone or clarithromycin-furazolidone compared to clarithromycin-based quadruple regimens for the eradication of Helicobacter pylori in peptic ulcer disease: a double-blind randomized controlled trial.

BACKGROUND: Furazolidone is a much cheaper drug with a very low resistance against Helicobacter pylori compared to clarithromycin. We aim to evaluate safety and efficacy of a sequential furazolidone-based regimen versus clarithromycin-based therapy in H. pylori eradication for ulcer disease. MATERIALS: Patients with proven peptic ulcer or duodenitis were randomized into three groups: OAB-M-F; metronidazole (M) (500 mg bid) for the first 5 days, followed by furazolidone (F) (200 mg bid) for the second 5 days; OAC-P; clarithromycin (C) (500 mg bid) for 10 days; and OAB-C-F; clarithromycin (500 mg bid) for the first 5 days and furazolidone (200 mg bid) for the second 5 days. All groups received omeprazole (O) (20 mg bid) and amoxicillin (A) (1 g bid). Groups OAB-M-F and OAB-C-F were also given bismuth subcitrate (B) (240 mg bid), whereas a placebo (P) was given to group OAC-P. Adverse events were scored and recorded. Two months after treatment, a C(13) -urea breath test was performed. RESULTS: Three hundred and ten patients were enrolled and 92 (OAB-M-F), 95 (OAC-P), and 98 (OAB-C-F) completed the study. The intention-to-treat eradication rates were 78.5% (95% CI = 69-85), 81.1% (95% CI = 73-88), and 82% (95% CI = 74-89), and per-protocol eradication rates were 91.3% (95% CI = 83-96), 90.4% (95% CI = 82-95), and 88.7% (95% CI = 81-94), for group OAB-M-F, OAC-P, and OAB-C-F, respectively. Eradication rate differences did not reach statistical significance. The most common adverse event, bad taste, occurred in all groups, but more frequently in groups OAC-P (34%) and OAB-C-F (32%), than OAB-M-F (14%) (p < .05). Adverse symptoms score were 0.88 ± 2.05 in group OAB-M-F, 1.15 ± 1.40 in group OAC-P, and 1.87 ± 1.62 in group OAB-C-F. CONCLUSION: Furazolidone can replace clarithromycin in H. pylori eradication regimens because of lack of development of resistance and very low cost.

Safety of furazolidone-containing regimen in Helicobacter pylori infection: a systematic review and meta-analysis.

OBJECTIVES: Furazolidone containing regimen is effectivefor Helicobacter pylori (H. pylori) infection, but its safetyremains controversial. To assess the safety of furazolidone containing regimenin H. pylori infection. DESIGN: A systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science and Scopus databases were systematically searched for eligible randomised controlled trials. ELIGIBILITY CRITERIA: Studies comparing furazolidone with non-furazolidone-containing regimen, variable durations or doses of furazolidone were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently selected studies and extracted data. Primary outcomes were the risk of total adverse events (AEs), serious AEs and severe AEs, expressed as relative risk (RR) with 95% CI. Secondary outcomes contained the incidence of individual adverse symptoms, AE-related treatment discontinuation and compliance. RESULTS: Twenty-six articles were identified from 2039 searched records, of which 14 studies (n=2540) compared furazolidone with other antibiotics. The eradication rates of furazolidone-containing regimen were higher than those of other antibiotics in both intention-to-treat (RR 1.06, 95% CI 1.01 to 1.12) and per-protocol analysis (RR 1.05, 95% CI 1.00 to 1.10). Only two serious AEs were reported in furazolidone group (2/1221, 0.16%). No significant increased risk was observed for the incidence of total AEs (RR 1.04, 95% CI 0.89 to 1.21) and severe AEs (RR 1.81, 95% CI 0.91 to 3.60). Twelve studies (n=3139) compared different durations of furazolidone, and four studies (n=343) assessed variable doses. Elevated risk of total AEs and severe AEs were only found in a high daily dose of furazolidone rather than prolonged duration. The incidence of AE-related treatment discontinuation and compliance of patients were all similar, irrespective of dose and duration adjustments. CONCLUSION: Furazolidone-containing regimen has a similar risk of AEs and compliance as non-furazolidone-containing regimen. A low daily dose of 200 mg is well-tolerated for 14 day regimen and should be first considered. PROSPERO REGISTRATION NUMBER: CRD42019137247.

Efficacy of a 7-day course of furazolidone, levofloxacin, and lansoprazole after failed Helicobacter pylori eradication.

BACKGROUND: Increasing resistance to clarithromycin and nitroimidazole is the main cause of failure in the Helicobacter pylori eradication. The ideal retreatment regimen remains unclear, especially in developing countries, where the infection presents high prevalence and resistance to antibiotics. The study aimed at determining the efficacy, compliance and adverse effects of a regimen that included furazolidone, levofloxacin and lansoprazole in patients with persistent Helicobacter pylori infection, who had failed to respond to at least one prior eradication treatment regimen. METHODS: This study included 48 patients with peptic ulcer disease. Helicobacter pylori infection was confirmed by a rapid urease test and histological examination of samples obtained from the antrum and corpus during endoscopy. The eradication therapy consisted of a 7-day twice daily oral administration of lansoprazole 30 mg, furazolidone 200 mg and levofloxacin 250 mg. Therapeutic success was confirmed by a negative rapid urease test, histological examination and 14C- urea breath test, performed 12 weeks after treatment completion. The Chi-square method was used for comparisons among eradication rates, previous treatments and previous furazolidone use. RESULTS: Only one of the 48 patients failed to take all medications, which was due to adverse effects (vomiting). Per-protocol and intention-to-treat eradication rates were 89% (95% CI- 89%-99%) and 88% (88-92%), respectively. Mild and moderate adverse effects were reported by 41 patients (85%). For patients with one previous treatment failure, the eradication rate was 100%. Compared to furazolidone-naïve patients, eradication rates were lower in those who had failed prior furazolidone-containing regimen(s) (74% vs. 100%, p = 0.002). CONCLUSION: An empiric salvage-regimen including levofloxacin, furazolidone and lansoprazole is very effective in the eradication of Helicobacter pylori, particularly in patients that have failed one prior eradication therapy.

Furazolidone, co-amoxiclav, colloidal bismuth subcitrate, and esomeprazole for patients who failed to eradicate Helicobacter pylori with triple therapy.

There is increasing evidence of Helicobacter pylori (H. pylori) resistance to the classical triple therapy consisting of a proton-pump inhibitor and clarithromycin with either amoxicillin or metronidazole. This study is aimed at establishing the efficacy and safety of a 14-day regimen to eradicate H. pylori in patients who have failed with the classical triple therapy given for 14 days. One hundred seventy-six patients diagnosed to have H. pylori infection were given triple therapy for 14 days. Fifty-two patients who failed to respond as evident from positive 14C-urea breath test (UBT) done 4-6 weeks after the completion of triple therapy were offered a combination regimen comprised of furazolidone 200 mg b.i.d, co-amoxiclav 1 g b.i.d., colloidal bismuth subcitrate 240 mg b.i.d., and esomeprazole 40 mg b.i.d. for 14 days. The mean age of these patients was 41 +/- 13 years (range 20-67). Thirty-four were males. To document eradication of H. pylori, UBT was repeated 4 weeks after the completion of treatment. On an intention-to-treat analysis, the eradication rate was 81% (42 out of 52) whereas on per-protocol basis, the eradication rate was 82.4% (42 out of 51). In conclusion, this new regimen represents a suitable second-line therapy.

Failure of Helicobacter pylori treatment after regimes containing clarithromycin: new practical therapeutic options.

UNLABELLED: Failure of Helicobacter pylori treatment is a growing problem in daily practice. AIM: To evaluate the efficacy of two new regimes as second-line options in a randomized and prospective study. METHODS: Patients in whom a first eradication regime containing clarithromycin had failed were included. After performing gastroscopy and a 13C-urea breath test (UBT), the patients were randomized to receive a combination of 20 mg of rabeprazole, 500 mg of levofloxacin, and 200 mg (two tablets) of furazolidone administered once daily for 10 days (RLF) or the combination of 20 mg of rabeprazole, 120 mg (two tablets) of bismuth subcitrate, 100 mg of doxycycline, and 200 mg of furazolidone, administered twice daily for 10 days (RBDF). Clinical examinations and new UBT were performed 60 days after therapy. RESULTS: Sixty patients were included (mean age, 46 years, 57% females). Two patients were excluded: one because of adverse effects and another as a result of protocol violation. Compliance was similar in both groups (90% took all medications correctly). Side-effects (96% mild) were observed in 87% of the patients and were comparable between groups, except diarrhea, which was more frequent in group RLF (p= .025). Intention-to-treat cure rates were 77% (95% confidence interval (CI): 62-93%) in the RLF group and 83% (95% CI: 68-97%) in the RBDF group (p= .750). Per-protocol cure rates were 80% (95% CI: 65-95%) in the RLF group and 82% (95% CI: 67-96%) in the RBDF group (p= 1.0). CONCLUSIONS: Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice-daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and furazolidone) for 10 days achieved encouraging results. Subsequent studies should be performed to evaluate antibiotic resistance, doses, dosing intervals, duration of treatment, and safety of these two regimes.

Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease.

AIM: To establish the efficacy and safety of a 7-d therapeutic regimen using omeprazole, bismuth subcitrate, furazolidone and amoxicillin in patients with peptic ulcer disease who had been previously treated with other therapeutic regimens without success. METHODS: Open cohort study which included patients with peptic ulcer who had previously been treated unsuccessfully with one or more eradication regimens. The therapeutic regimen consisted of 20 mg omeprazole, 240 mg colloidal bismuth subcitrate, 1000 mg amoxicillin, and 200 mg furazolidone, taken twice a day for 7 d. Patients were considered as eradicated when samples taken from the gastric antrum and corpus 12 wk after the end of treatment were negative for Helicobacter pylori (H pylori) (rapid urease test and histology). Safety was determined by the presence of adverse effects. RESULTS: Fifty-one patients were enrolled. The eradication rate was 68.8% (31/45). Adverse effects were reported by 31.4% of the patients, and these were usually considered to be slight or moderate in the majority of the cases. Three patients had to withdraw from the treatment due to the presence of severe adverse effects. CONCLUSION: The association of bismuth, furazolidone, amoxicillin and a proton-pump inhibitor is a valuable alternative for patients who failed to respond to other eradication regimens. It is an effective, cheap and safe option for salvage therapy of positive patients.

Physicochemical and in vitro biological evaluations of furazolidone-based ß-cyclodextrin complexes in Leishmania amazonensis.

Recently, there have been numerous cases of leishmaniasis reported in different Brazilian states. The use of furazolidone (FZD) to treat leishmaniasis has been previously described; however, the drug is associated with adverse effects such as anorexia, weight loss, incoordination, and fatigue in dogs. Thus, in the present study, we prepared and evaluated inclusion complexes between FZD and ß-cyclodextrin (ß-CD) to guarantee increased drug solubility and reduce the toxicity associated with high doses. The FZD:ß-CD complexes were prepared by two different techniques (kneading and lyophilization) prior to incorporation in an oral pharmaceutical dosage form. Formation of the complexes was confirmed using appropriate physicochemical methods. Antileishmanial activity against L. amazonensis was tested in vitro via a microplate assay using resazurin dye and cytotoxicity was determined using the fibroblast L929 lineage. Solubility studies showed the formation of complexes with complexation efficiencies lower than 100%. Physicochemical analysis revealed that FZD was inserted into the ß-CD cavity after complexation by both methods. Biological in vitro evaluations demonstrated that free FZD and the FZD:ß-CD complexes presented significant leishmanicidal activity against L. amazonensis with IC50 values of 6.16 µg/mL and 1.83 µg/mL for the complexes prepared by kneading and lyophilization, respectively. The data showed that these complexes reduced the survival of promastigotes and presented no toxicity for tested cells. Our results indicate that the new compounds could be a cost-effective alternative for use in the pharmacotherapy of leishmaniasis in dogs infected with L. amazonensis.