Tinidazole for the treatment of vaginal infections.

Tinidazole has been used for vaginal infection worldwide but not in the US for > 40 years. Recently, tinidazole has been re-introduced and approved by the FDA for trichomoniasis and restudied as an alternative to metronidazole for bacterial vaginosis. In vitro antimicrobial activity and pharmacokinetics studies indicate that tinidazole has minor but possibly relevant antimicrobial as well as pharmacokinetic advantages when compared directly with metronidazole. Clinical comparison has been infrequent although the limited head-to-head studies indicate minimal therapeutic advantage with tinidazole. Perhaps the more relevant differences relate to the enhanced tolerance and reduced toxicity of tinidazole. Ongoing, as yet incomplete, studies directly comparing the clinical efficacy of metronidazole and tinidazole for bacterial vaginosis should clarify the status of tinidazole; however, cure rates are unlikely to be significantly different. Although uncommon, high-level trichomonal metronidazole resistance can be reliably cured by using tinidazole, which is an invaluable advantage.

A study of 4- and 7-day triple therapy with rabeprazole, high-dose levofloxacin and tinidazole rescue treatment for Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori treatment failure is becoming an emergent problem in clinical practice. Shorter treatment duration should improve compliance to therapy and keep an acceptable H. pylori eradication rate. AIMS: To evaluate the efficacy of two rabeprazole, high-dose levofloxacin and tinidazole-based regimens as 'rescue' treatment for H. pylori eradication in an open-label, randomized, pilot study carried out in a clinical practice setting. METHODS: Eighty-five consecutive patients who have previously failed at least one H. pylori eradication attempt were randomized to receive rabeprazole (20 mg, b.d.), levofloxacin (500 mg, b.d.) and tinidazole (500 mg, b.d.) either for 4 (4-day RLT, n = 42) or 7 days (7-day RLT, n = 43). Cure of H. pylori infection was assessed by means of 13C-urea breath test. RESULTS: The 7-day RLT achieved 84% (95% CI: 69-93%) and 86% (95% CI: 72-95%) eradication rates in intention-to-treat and per-protocol analyses respectively. The shorter treatment obtained an 83% (95% CI: 69-93%) eradication rate in both intention-to-treat and per-protocol analysis. Both regimens were well tolerated, although patients who received the 4-day RLT reported fewer side-effects. CONCLUSIONS: In patients who have previously failed at least one H. pylori eradication attempt, both 4- and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens are effective in curing the infection in more than 80% of patients.

[Clinical efficacy of a novel antimicrobial drug combination containing ciprofloxacin and tinidazole in the treatment of patients with skin and soft tissue infections].

Clinical and microbiological efficacies of a combined drug, a fixed combination of ciprofloxacin and tinidazole in the form of tablets (Cifran ST, Ranbaxy, India) were studied. The drug was given to 40 patients with skin and soft tissue infections in the complex surgical treatment. The clinical effect and bacteriological efficacy were observed in 97.5 and 75% of the cases respectively. The drug tolerability was good and no adverse reactions were stated.

Moxifloxacin-based strategies for first-line treatment of Helicobacter pylori infection.

BACKGROUND: Standard anti-Helicobacter pylori therapy may not achieve a satisfactory eradication rate. Fluoroquinolones, such as moxifloxacin, are safe and promising agents for H. pylori eradication. AIM: To compare the efficacy of two 1-week moxifloxacin-based H. pylori eradication regimens with two standard treatments. METHODS: Three hundred and twenty H. pylori-positive subjects were randomized into four groups to receive: moxifloxacin, amoxicillin, esomeprazole (Group MAE); moxifloxacin, tinidazole and esomeprazole (Group MTE); standard triple therapies with clarithromycin, amoxicillin and esomeprazole (Group CAE) or tinidazole (Group CTE) for 7 days. H. pylori status was re-assessed 6 weeks after the end of therapy by 13C urea breath test. RESULTS: Three hundred and twenty patients completed the efficacy analysis per protocol; H. pylori eradication rate in group MTE was 90% (72 of 80) and 92% (72 of 78), in group MAE was 88% (70 of 80) and 89%, (70 of 79) in Group CAE was 73% (58 of 80) and 78% (58 of 74), and in Group CTE was 75% (60 of 80) and 79% (60 of 76), respectively, in intention-to-treat and in per protocol analyses. Eradication rates of moxifloxacin-based triple therapies were significantly higher than that observed using standard triple schemes. The incidence of side effects was significantly lower in moxifloxacin groups than in control groups. CONCLUSIONS: Seven-day moxifloxacin-based triple therapies provide optimal eradication rates with a good compliance when compared with the standard triple therapy schemes.

Famotidine versus omeprazole, in combination with amoxycillin and tinidazole, for eradication of Helicobacter pylori infection.

BACKGROUND: Eradication regimens combining two antibiotics with a proton pump inhibitor have been studied intensively. In contrast, only a few studies have focused on the possible role of H2-receptor antagonists in eradication therapy. The mechanism involved in the synergy between antibiotics and proton pump inhibitors is still controversial. OBJECTIVES: To compare the results of two triple-therapy regimens, different only in the antisecretory drugs used, in patients with Helicobacter pylori infection, and to assess the impact of primary resistance to metronidazole on treatment outcome. METHODS: A total of 120 patients with peptic ulcer and non-ulcer dyspepsia were randomly assigned to a 2-week course of either: famotidine 40 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (FAT group; n = 60); or omeprazole 20 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (OAT group; n = 60). Upper endoscopy was performed prior to treatment and at least 4 weeks after completion of treatment and discontinuation of the antisecretory therapy. H. pylori status was assessed by a biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 48 of the 60 patients (80%; 95% confidence interval: 70-90%) in the FAT group, compared to 50 of the 60 patients (83.3%; 95% confidence interval: 74-93%) in the OAT group. In the per protocol analysis, eradication therapy was achieved in 48 out of 53 patients (90.6%; 95% confidence interval: 83-98%) treated with FAT and 50 out of 57 patients (87.7%; 95% confidence interval: 79-96%) treated with OAT (not significant). The primary metronidazole resistance was present in 28.8% of strains. Overall, per protocol eradication rates in strains resistant and susceptible to metronidazole were 83.3% and 91.3% respectively (P > 0.05). CONCLUSIONS: Two-week courses of either high-dose famotidine or omeprazole, both combined with amoxycillin and tinidazole, are equally effective for eradication of H. pylori infection. In a 2-week triple therapy, metronidazole resistance has no significant impact on eradication rates.

Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side effects during Helicobacter pylori eradication therapy: a pilot study.

BACKGROUND: One-week triple therapy is currently regarded as the reference of anti-Helicobacter pylori treatment. However, antibiotic-associated gastrointestinal side effects are among the major pitfalls of such regimens. Probiotic supplementation may be regarded as a therapeutic tool to prevent or reduce these troublesome drug-related manifestations. AIM: To determine whether the addition of the probiotic Lactobacillus GG to an anti-H. pylori standard triple therapy could help to prevent or minimize the occurrence of gastrointestinal side effects. METHODS: One hundred and twenty healthy asymptomatic subjects screened positive for H. pylori infection and deciding to receive eradication therapy were randomized either to 1-week pantoprazole (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), tinidazole (500 mg b.i.d.) or to the same regimen supplemented with Lactobacillus GG for 14 days. Patients filled in validated questionnaires during follow-up to determine the type and severity of side effects and to judge overall tolerability. RESULTS: Bloating, diarrhea and taste disturbances were the most frequent side effects during the eradication week and were significantly reduced in the Lactobacillus GG-supplemented group (RR = 0.4, CI 0.2-0.8; RR = 0.3, CI 0.1-0.8; RR = 0.3, CI 0.1-0.7, respectively). The same pattern was observed throughout the follow-up period. Overall assessment of treatment tolerability showed a significant trend in favor of the Lactobacillus GG-supplemented group (p = 0.03). CONCLUSIONS: Lactobacillus GG supplementation beneficially affects H. pylori therapy-related side effects and overall treatment tolerance.

The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy.

BACKGROUND: One-week triple therapy is currently considered the golden standard against Helicobacter pylori. However, gastrointestinal side-effects are among the major pitfalls in such regimens. Probiotic supplementation might help to prevent or reduce such drug-related manifestations. AIM: To determine whether adding the probiotic Lactobacillus GG to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden. METHODS: Sixty healthy asymptomatic subjects screened positive for H. pylori infection were randomized to 1 week rabeprazole (20 mg b.d.), clarithromycin (500 mg b.d.), tinidazole (500 b.d.) and the probiotic Lactobacillus GG for 14 days or to the same regimen with a placebo preparation. Patients completed validated questionnaires during the week of treatment and during the following 3 weeks, to determine the type and severity of side-effects and an overall judgement of tolerability. RESULTS: Diarrhoea, nausea and taste disturbance were significantly reduced in the Lactobacillus GG supplemented group (relative risk=0.1, 95% CI: 0.1-0.9; relative risk=0.3, 95% CI: 0.1-0.9; relative risk=0.5, 95% CI: 0.2-0.9, respectively). An overall assessment of treatment tolerability showed a significant difference in favour of the Lactobacillus GG supplemented group (P=0.04). CONCLUSIONS: Lactobacillus GG supplementation showed a positive impact on H. pylori therapy-related side-effects and on overall treatment tolerability.

Five-day regimens containing ranitidine bismuth citrate plus high-dose clarithromycin and either amoxycillin or tinidazole for Helicobacter pylori infection.

BACKGROUND: Ranitidine bismuth citrate (RBC)-based triple therapies for a period of 7 days have proved to be an effective treatment for Helicobacter pylori. AIM: To investigate the eradication efficacy, safety profile and patient compliance of two RBC-based triple therapies given for 5 days. METHODS: Eighty H. pylori-positive patients with dyspeptic symptoms, referred to us for gastroscopy, were consecutively enrolled in this prospective, randomized, open-label study. These patients were randomly assigned to receive a 5-day course of RBC 400 mg b.d. plus clarithromycin 500 mg b.d. and either tinidazole 500 mg b.d. (RBCCT group) or amoxycillin 1 g b.d. (RBCCA group). The H. pylori status was assessed by means of histology and rapid urease test at entry, and by 13C-urea breath test 8 weeks after the completion of treatment. RESULTS: All enrolled patients completed the study. Thirty-seven of 40 patients treated with RBCCT (both PP and ITT analysis: 93%; 95% CI: 80-98%) and 35 of 40 in the RBCCA group (both PP and ITT analysis: 88%; 95% CI: 73-96%) returned H. pylori-negative. Slight or mild side-effects occurred in 4/40 patients (10%) in the RBCCT group and in 5/40 (12%) in the RBCCA group. CONCLUSIONS: This is the first study demonstrating the efficacy of RBC-based triple therapies given for only 5 days. RBC regimens containing high-dose clarithromycin and either amoxycillin or tinidazole prove to be well tolerated, safe and preserve good eradication rates even when administered for a shorter than conventional duration.

Antibiotic versus maintenance therapy in the prevention of duodenal ulcer recurrence. Results of a multicentric double-blind randomized trial.

OBJECTIVES: Reduction of gastric acid secretion by maintenance therapy and eradication of Helicobacter pylori by antibiotic treatment have been shown to reduce duodenal ulcer relapse. This study compared the effect of two regimens, a 6-month maintenance on an H2 receptor antagonist versus a one-week antibiotic therapy, on the rate of duodenal ulcer relapse in duodenal ulcer patients with gastric H. pylori infection. METHODS: We conducted a 30-week, double-blind, double-dummy, multicentric clinical trial involving 119 patients (97 M, 22 F, mean age 39 +/- 14 years) randomly assigned to a daily dose of 40 mg famotidine for 6 weeks supplemented with, during the first week, either antibiotics (500 mg amoxicillin q.i.d. and 500 mg tinidazole t.i.d.-antibiotic group) or their placebo (maintenance group). Healed patients after 6 weeks entered the 6-month maintenance phase: the maintenance group received 20 mg famotidine at bedtime and the antibiotic group, a placebo. Endoscopy with antral biopsies was performed to allow a rapid urease test, culture and histological examination upon entry, after 6 weeks, 3 months, and 6 months and, whenever symptoms recurred. H. pylori status was regarded as positive if any one of these three tests was positive, and negative if all tests were negative. RESULTS: The 2 treatment groups were well balanced for all baseline characteristics. After 6 weeks, H. pylori was eradicated in 25 (45%) patients in the antibiotic group, and in 1 (2%) in the maintenance group (P < 0.01). In term of intention-to-treat, there was no significant difference in the healing rate after 6 weeks (93 and 83% in the antibiotic and maintenance groups, respectively; P = 0.15) or in the relapse rate after 6 months (13 and 28% in the antibiotic and maintenance groups, respectively; P = 0.17 Log-rank test). However, the overall failure rate (absence of healing, relapse) was lower (P = 0.04, Log-rank test) in the antibiotic group in which all relapses but one were observed in H. pylori positive patients. The rate of ulcer relapse (1/20) in patients of antibiotic group who remained free of H. pylori during the study, was significantly (P < 0.01) lower compared with that of H. pylori positive patients in the maintenance group (11/44). During the first 6-week period, more side effects were observed in the antibiotic group than in the maintenance group (4 vs 1 patient, respectively). CONCLUSIONS: Our results indicate no significant difference between ulcer relapse rates after 6 months following a one-week antibiotic therapy or long-term maintenance therapy. Short-term antibiotic therapy should be considered as a valuable alternative to the long-term maintenance therapy.