Safety Of Metronidazole Research Articles

Genotoxicity from metronidazole detected in vitro, but not in vivo, in healthy dogs in a randomized clinical trial.

To determine whether metronidazole (MTZ), at recommended therapeutic dosages in dogs, induces peripheral blood cell (PMBC) genotoxicity, using the γ-H2AX assay as a sensitive measure of DNA breaks. The secondary aim was to assess dose-dependent genotoxicity in vitro in dog and cat PBMCs exposed to increasing MTZ concentrations. 12 healthy employee- and student-owned dogs and blood samples from 2 other healthy untreated dogs and 2 healthy untreated cats. Screened dogs were randomized to receive lower-dose MTZ (7.5 mg/kg, PO, q 12 h) or higher-dose MTZ (20 mg/kg, PO, q 12 h) for 7 days. Blood was drawn at baseline, after the 1 week of treatment, and after a 1-week washout, for DNA damage assessment and serum MTZ concentration measurements. For in vitro studies, PBMCs from untreated healthy dogs and cats were exposed to 0 to 500 μg/mL MTZ. No dogs showed a significant increase in DNA damage at these MTZ dosages for 1 week. The highest serum MTZ concentration observed 1 hour after dosing was 36 μg/mL. In vitro, MTZ led to a significant increase in DNA damage at 100 μg/mL in both canine and feline PBMCs. Although MTZ was not significantly genotoxic in vivo in the healthy dogs in this study, MTZ was significantly genotoxic to canine PBMCs in vitro at 3-fold higher concentrations than those documented in vivo. The safety of MTZ in clinically ill dogs, which may have impaired MTZ clearance or DNA repair, should be assessed next.

Feasibility study and evaluation of expert opinion on the semi-automated meta-analysis and the conventional meta-analysis.

To assess the feasibility and acceptance of the semi-automated meta-analysis (SAMA). The objectives are twofold, namely (1) to compare expert opinion on the quality of protocols, methods, and results of one conventional meta-analysis (CMA) and one SAMA and (2) to compare the time to execute the CMA and the SAMA. Experts evaluated the protocols and manuscripts/reports of the CMA and SAMA conducted independently on the safety of metronidazole in pregnancy. Expert opinion was collected using AMSTAR 2 checklist. Time spent was recorded using case report forms. The overall scores of the opinion of all experts for protocols, methods, and results for SAMA (6.75) and CMA (6.87) were not statistically different (p = 0.88). The experts' confidence in the results of each MA was 7.89 ± 1.17 and 8.11 ± 0.92, respectively. The time to completion was 14 working days for SAMA and 24.7 for CMA. MA tasks such as calculation of effect estimates, subgroup/sensitivity analysis, and publication bias investigation required no investment in time for SAMA. In conclusion, our study demonstrated the feasibility of SAMA and suggests acceptance for risk assessment by an expert committee. Our results suggest that SAMA reduces the time required for a MA without altering expert confidence in the methodological and scientific rigor. As our study was limited to one example, the generalization of our results requires confirmation by other studies.

Retrospective study of the efficacy and safety of metronidazole and vancomycin for Clostridioides difficile infection

IntroductionAccording to the Japanese guidelines for the management of Clostridioides difficile infection (CDI), the first choice is metronidazole (MNZ) for non-severe cases and vancomycin (VCM) for severe cases. However, the appropriateness of this first choice in Japanese patients is unclear. We therefore evaluated the appropriateness of the CDI management guidelines and the incidence of adverse drug reactions. MethodsThe electronic chart data at Keio University Hospital between January 2012 and June 2019 were retrospectively reviewed. The response rate, the relapse rate, and the adverse reaction rate of treatment for CDI using MNZ or VCM were investigated according to the disease severity. Factorial analysis associated with the response, relapse, and adverse reaction was also performed. ResultsIn the 352 patients surveyed, no significant difference was observed in the response rate between MNZ and VCM regardless of the severity of CDI. The presence of cancer was a factor related to the persistence of diarrheal symptoms and older age was a risk factor for relapse. MNZ induced nausea significantly more frequently than VCM, and young age and female sex were risk factors for nausea. ConclusionAs no significant difference was observed in the response rate of CDI between MNZ and VCM, the Japanese CDI management guidelines, which recommend MNZ as the first choice, were demonstrated to be appropriate. Attention to nausea was also suggested to be necessary when administering MNZ to young females.

Investigating the efficacy and safety of metronidazole during pregnancy; A systematic review and meta-analysis.

ObjectiveWe aimed to review and analyze studies focusing on the efficacy of metronidazole in reducing the risk of preterm birth and the safety of metronidazole taking into account the different doses, duration of treatment and routes of administration.Study designsEmbase, Cochrane Library and PubMed were searched up to 29 July 2019 to identify studies assessing metronidazole exposure during pregnancy. Additional studies were identified from reference lists of retrieved papers. Measured outcomes were preterm births (<37 weeks of gestation) and associated delivery outcomes such as spontaneous abortions (≤ 20 weeks of gestation), stillbirths (≥20 weeks of gestation) and low birth weight (<2500 g) irrespective of the period of exposure and major malformations after first-trimester exposure. Overall effect estimates for RCTs and observational studies were calculated using the random-effects model and pooled using Risk Ratios (RR) and Odds Ratios (OR) respectively. ROB-2 and ROBINS-I tool were used to assess Risk of Bias for RCTs and observational studies, respectively.ResultsTwenty-four studies (17 observational studies and 7 RCTs) were selected. Pooled RR was 1.10 (95 % CI 0.78–1.55; n = 7; I2 = 72 %) for preterm birth. Subgroup analysis found RR 1.67; 95 % CI 1.07–2.62; n = 3; I² = 32 %) for treatment duration of ≤3 days among women with a previous preterm delivery. Pooled OR for spontaneous abortion was 1.72 (95 % CI 1.40–2.12; n = 5; I2 = 72 %) and 1.15 (95 % CI 0.98–1.34; n = 12; I2 = 25 %) for major malformations. After exclusion of studies with critical risk of bias, pooled OR were 1.7 (1.42–2.04; n = 3; I2 = 19 %) and 1.13 (0.93–1.36; n = 9; I2 = 28 %) respectively. Among several specific malformations analyzed, only congenital hydrocephaly was significantly increased at 4.06 (95 % CI 1.75–9.42; n = 2; I² = 0%).ConclusionsData do not confirm the efficacy of metronidazole in reducing the risk of preterm birth and associated delivery outcomes. Further research is required to confirm the effect of high dose and short duration of metronidazole treatment on preterm birth among the high-risk group. Regarding the increased odds of spontaneous abortion, RCTs are required to assess the role of the underlying infection. The need for further studies to confirm the risk of congenital hydrocephaly is paramount.

Antimicrobial therapy ofClostridium difficileinfection. Systematic literature review and meta-analysis

Introduction:Clostridium difficile is the leading cause of antibiotic associated infectious nosocomial diarrhoea. Limited number of new pharmaceutical products have been developed and registered in the past decades for the treatment of Clostridium difficile infection. The available scientific evidence is limited and hardly comparable. Aim: To analyse the clinical efficacy and safety of metronidazole, vancomycin and fidaxomicin in the therapy of Clostridium difficile infection. Methods: Systematic review and meta-analysis of the literature data. Results: Meta-analysis of literature data showed no significant difference between these antibiotics in clinical cure endpoint (odss ratios: fidaxomicin vs. vancomycin 1.19; vancomycin vs. metronidazol 1.69 and fidaxomicin vs. metronidazol 2.00). However, fidaxomicin therapy was significantly more effective than vancomicin and metronidazol in endpoints of recurrence and global cure (odds ratios: fidaxomicin vs. vancomycin 0.47; vancomycin vs. metronidazol 0.91 és fidaxomicin vs. metronidazol 0.43). There was no significant difference between fidaxomicin, vancomycin and metronidazole in safety endpoints. Conclusions: Each antibiotic similarly improved clinical cure. Fidaxomicin was the most effective therapeutic alternative in lowering the rate of recurrent Clostridium difficile infections. Orv. Hetil., 2013, 154, 890–899.

RELATIONSHIP BETWEEN METRONIDAZOLE AND CO-TRIMOXAZOLE ON ERADICATION OF ENTAMOEBA HISTOLYTICA

To present the efficacy and safety of Metronidazole and co-trimoxazole in the treatment of diarrhea ca used by Entamoeba histolytica, cyst and trophozyed in pa tients presented to the emergency department and emergency pediatric clinic in Queen Alia Hospital ( Jordan). A strategy for diagnosis Entamoeba histoly tica was evaluated by studying 181 patients aged 2-50 ye ars. Between the 1st of May 2009 and the beginning of May 2010, 181 patients with intestinal amoebiasis w ere recruited for this study from the Emergency Department and emergency Pediatric Clinic at Queen Alia Military Hospital. After doing stool analysis for every patient, Metronidazole 500 mg three times was given to the adult group and 40 mg kg -1 day in three divided doses for the pediatric group for 10 days a nd two tablets twice daily for adults and 5 mL twic e daily for children for ten days of co-trimaxazole, with f ollow up stool analysis after one week of treatment . Out of 181 patients (81) patients were adult’s age (14-50 years) and (100 patients) were children aged (2-14 years). About 5.5% of the patient showed the amoebic trophozoite in their stool while the remaining showed onl y the amoebic cysts. Over all metronidazole and co-tr imoxazole produced a clinical response rate of 95% in both adults and children group after 10 days course of Metronidazole. Our findings demonstrated the efficacy of 10 day of course Metronidazole and co-t rimoxazole in eradication intestinal amoebiasis for which the causative organism is identified by simpl e stool examination.

Liver abscess presentation and management in Saudi Arabia and the United Kingdom

BACKGROUND AND OBJECTIVES:Liver abscess (LA) is a well-described disease in the medical literature; however, information about its characteristics and outcome in the Middle East is lacking. We compared the mode of presentation, risk factors, management and outcome of LA patients in Saudi Arabia with cases from the United Kingdom (UK).DESIGN AND SETTING:Retrospective review of LA patients from three tertiary care centers (2 from Saudi Arabia and 1 from the UK) over a period of 10 years, from 1995 to 2005.PATIENTS AND METHODS:Data collected included demographic characteristics; clinical presentation; biochemical, microbiological and radiological findings; treatment modalities; and outcome.RESULTS:A total of 83 patients were diagnosed with LA, including 48 patients from Saudi Arabia and 35 patients from the UK. The mean (SD) age was 45.2 (20.3) years for those from Saudi Arabia and 55.4 (18.8) years for those from the UK (P=.022). The majority of the patients were males (70% from Saudi Arabia and 80% from the UK). Upper abdominal pain and fever were the commonest symptoms, each reported in 87% of the cases. Alkaline phosphatase elevation was the commonest liver function abnormality, seen in 66 (80%) patients. Organisms were isolated in 43 (52%) cases and the majority of these were coliforms (58%). Amebic liver abscesses occurred in 19 (23%) patients and all of those patients were either from or had traveled recently to the Indian subcontinent. Complete resolution of the abscesses was achieved in 66 (80%) patients with aspiration and/or antibiotics, and 9 (10.8%) patients died. On multivariate analysis, underlying malignancy, hypotension and chest signs at presentation were predictors of poor outcome (P=.008, .029 and .001, respectively).CONCLUSIONS:Successful resolution of LA is achievable in the majority of the cases, although underlying malignancy is associated with poor outcome. Amebic liver abscesses must be considered in patients with a history of travel to endemic areas.

Ciprofloxacin or metronidazole for the treatment of perianal fistulas in patients with Crohnʼs disease: A randomized, double-blind, placebo-controlled pilot study

Although metronidazole and ciprofloxacin are used to treat perianal Crohn's disease (CD), no placebo-controlled trials have been performed. We performed a placebo-controlled pilot trial to evaluate the efficacy and safety of metronidazole and ciprofloxacin in patients with perianal CD. Twenty-five patients with CD and actively draining perianal fistulas were randomized to receive ciprofloxacin 500 mg, metronidazole 500 mg, or placebo twice daily for 10 weeks. Remission and response of perianal fistulas were defined as closure of all fistulas and closure of at least 50% of fistulas that were draining at baseline, respectively. The primary endpoint was remission at 10 weeks. Ten patients were randomized to ciprofloxacin, 7 to metronidazole, and 8 to placebo. Remission at week 10 occurred in 3 patients (30%) treated with ciprofloxacin, no patients (0%) treated with metronidazole, and 1 patient (12.5%) treated with placebo (P = 0.41). Response at week 10 occurred in 4 patients (40%) treated with ciprofloxacin, 1 patient (14.3%) treated with metronidazole, and 1 patient (12.5%) treated with placebo (P = 0.43). Termination of the trial prior to week 10 occurred in 1 patient (10%) treated with ciprofloxacin, 5 patients (71.4%) treated with metronidazole, and 1 patient (12.5%) treated with placebo (P < 0.02). No serious adverse events occurred. Remission and response occurred more frequently in patients treated with ciprofloxacin but the differences were not significant in this pilot study. Ciprofloxacin was well tolerated.

Metronidazole 0.75% gel vs. ketoconazole 2% cream in the treatment of facial seborrheic dermatitis: a randomized, double‐blind study

Recently, two placebo-controlled studies have shown that topical metronidazole was effective in the treatment of seborrheic dermatitis. To compare the efficacy and safety of metronidazole 0.75% gel with that of ketoconazole 2% cream in the treatment of facial seborrheic dermatitis. A total of 60 consecutive patients with facial seborrheic dermatitis were included. Patients were randomized into two groups. One group used ketoconazole 2% cream with metronidazole gel as vehicle; the other group used metronidazole 0.75% gel with ketoconazole cream as vehicle for a 4-week treatment period. Main outcome measures were change in clinical severity scores, patients' and investigator's global evaluation of improvement and frequency of side-effects. All the assessments were made by an investigator who was unaware of which group the patients were allocated to. Mean percentage decrease in clinical severity scores from baseline to last available visit was 63.4% (95% CI 57.7-69) and 54.4% (95% CI 47.9-61) in the ketoconazole- and metronidazole-treated patients, respectively (P = 0.31). Eighty-two per cent of patients in the ketoconazole group vs. 79% of patients in the metronidazole group rated their global improvement as significant or moderate (P > 0.05). No statistically significant difference in the frequency of side-effects was detected between the two groups. The results of this study need to be confirmed in further studies involving large numbers of patients. Our data demonstrated that metronidazole 0.75% gel had a comparable efficacy and safety profile with that of ketoconazole 2% cream in the treatment of facial seborrheic dermatitis.

Randomized, Single-Blind, Placebo-Controlled Multicenter Trial to Compare the Efficacy and Safety of Metronidazole and Satranidazole in Patients With Amebic Liver Abscess

The aims of our randomized, single-blind trial involving 49 patients were to study the efficacy, side effects, and tolerance of metronidazole and satranidazole in patients of amebic liver abscess. Twenty-five patients received metronidazole (800 mg TID) and 24 received satranidazole (300 mg TID with placebo at mealtime). Patients recorded side effects and tolerability through a performa. The time taken for resolution of fever and pain and the fall in abscess size was not significant. However, tolerance of satranidazole as reported by the patients was significantly better than metronidazole (P < .005). The incidence of adverse effects was significantly lower in the group given satranidazole (P < .005). The incidence of nausea and metallic taste was significantly lower in the patients given satranidazole (P < .005). Thus, despite having a similar efficacy, satranidazole showed a far lower incidence of side effects and had a significantly better tolerance than Metronidazole.

Comparison of the clinical efficacy and safety of metronidazole 0.75% cream with metronidazole 0.75% gel in the treatment of rosacea

Comparison of the clinical efficacy and safety of metronidazole 0.75% cream with metronidazole 0.75% gel in the treatment of rosacea

Safety of metronidazole in pregnancy: A meta-analysis

OBJECTIVE: Our purpose was to determine from published experience in humans whether metronidazole exposure during the first trimester of pregnancy is associated with an increased teratogenic risk. STUDY DESIGN: All published articles reporting on metronidazole use during pregnancy were screened by two independent reviewers to select those including pregnant patients exposed during the first trimester and comparing the outcomes of their pregnancies with that of patients either not exposed to metronidazole or exposed only during the third trimester. The outcome under consideration was the occurrence of birth defects in live-born infants. The overall odds ratios of first-trimester exposure versus no first-trimester exposure was calculated by combining the selected studies in a meta-analysis according to the procedure of Mantel and Haenszel. RESULTS: From 32 identified studies, 7 met the inclusion criteria for meta-analysis. Six were prospective and included 253 women exposed to the drug in the first trimester of pregnancy; one was retrospective and reported on 1083 exposed women. The overall weighted odds ratio of exposure versus no exposure during the first trimester calculated by meta-analysis of the 7 studies was 0.93 (95% confidence interval 0.73 to 1.18). The odds ratio calculated from the 6 prospective studies was 1.02 (95% confidence interval 0.48 to 2.18). CONCLUSION: Metronidazole does not appear to be associated with an increased teratogenic risk.

Swine dysentery control in the German Democratic Republic and the suitability of injections of tiamulin for the programme.

In 1977 swine dysentery was made a notifiable disease in the German Democratic Republic, with the intention of eradicating it by the systematic treatment of clinically affected herds using intensive medication and hygiene control programmes. On individual farms the scheme appeared to be successful, but the national incidence of the disease did not decline, owing to the continuous presence of latently infected herds and the movement of carrier pigs to uninfected farms. In 1981 the scheme was re-appraised and a new scheme was introduced in one region where all the breeding herds were screened for the presence of Treponema hyodysenteriae; all positive herds were treated with either metronidazole or tylosin, and the movement of pigs into the region was controlled. This programme effectively eradicated the disease from the region and is being introduced to the rest of the country. Owing to concern about the safety of metronidazole and the development of resistance to tylosin, alternative antimicrobials were examined and tiamulin was selected to assess its suitability for inclusion in the programme. A 560 sow breeding herd and progeny were treated for five days with tiamulin at 10 mg/kg bodyweight. This was coupled with extensive cleaning, disinfection and rodent control programmes. The results of the trial showed that the clinical disease stopped in two days and that no further clinical signs were seen in the subsequent two-and-a-half years. Bacterial monitoring of faeces samples and colonic scrapings from dead pigs failed to identify viable T hyodysenteriae. There was a significant increase of 0.6 piglets weaned per litter and improvements in weaning weights and growth rates. It was concluded that tiamulin was suitable for inclusion in the swine dysentery eradication programme in the GDR.

Use of a time-kill technique for susceptibility testing of Trichomonas vaginalis.

The emergence of metronidazole-resistant Trichomonas vaginalis and questions about the safety of metronidazole are significant concerns in treatment of trichomoniasis. At 24 h, a microtiter assay was used to test antimicrobial susceptibility of 16 recent isolates; the MICs of metronidazole ranged from less than 0.06 to 25 micrograms/ml. Observable motility as an endpoint correlated imperfectly with survival as measured in pour plates. Quantitative pour plate cultures of six T. vaginalis isolates after timed exposures to antimicrobial drugs demonstrated exquisite sensitivity to metronidazole with minimal trichomonacidal concentrations of 0.025 to 0.100 micrograms/ml. Killing of some T. vaginalis isolates by clotrimazole and rosoxacin occurred only at concentrations of 100 micrograms/ml. Resistance to both rosoxacin and clotrimazole correlated with increasing resistance to metronidazole (P less than 0.01).

Treatment of Trichomonas vaginalis Infections

dal agent available in the United States. Although the drug is highly effective, recent concerns regarding the safety of metronidazole [2] and the documentation of clinically resistant infections [3-7] indicate a need for a reappraisal of the current and future treatment of infections due to T. vaginalis. The purpose of this paper is to review the scientific literature to develop a perspective on current and future therapeutic strategies in the treatment and control of Trichomonas vaginalis infections.