Use Of Oral Metronidazole Research Articles

The frequency and duration of side-effects associated with the use of oral metronidazole; A prospective study of VITA trial participants.

The tolerability of metronidazole is often perceived as being poor and in particular as being a cause of gastrointestinal side effects, but the frequency, severity and duration of adverse effects (AE) is not well characterised. This study assessed the frequency and type of metronidazole associated AEs in women treated for bacterial vaginosis. An exploratory study of participants from the lactic acid gel versus metronidazole for treating bacterial vaginosis (VITA) randomised controlled trial. In this sub-study, women aged ≥16years, diagnosed with bacterial vaginosis and who received oral MTZ (400mg twice daily, for 7days) were followed up prospectively over 2weeks. Baseline demographic and clinical data, and self-reported data on the incidence, time to onset, and duration of AEs were analysed. 155 women were included, of whom 64% (99/155) reported at least one metronidazole AE, including 47% (72/155) who reported gastrointestinal symptoms (nausea and/or vomiting [52/155], abdominal pain [31/154] or diarrhoea [31/154]) mostly within 3days of starting treatment and resolving within 5days of onset. Treatment discontinuation occurred in 8% (12/148) overall and AEs were given as the reason for discontinuing in only 3% (4/148). Overall, metronidazole side effects occurred commonly, but resolved within a few days and had a limited impact on treatment completion.

P03 Improving antimicrobial stewardship and sustainability by promoting oral metronidazole in eligible surgical patients at the Royal Alexandra Hospital

BackgroundAntimicrobial stewardship (AS) is essential to minimize the emergence and spread of antimicrobial resistance.1 Timely IV to oral antibiotic switch and promotion of the oral route are key AS initiatives in the acute hospital setting.1 Metronidazole is commonly prescribed IV in the surgical management of intra-abdominal sepsis; however, metronidazole has excellent oral bioavailability of 95%–100%. In addition to improved AS, the oral route provides advantages to patients, staff and the environment including reduced patient risk of line infections/complications; reduced staff workload and healthcare costs; improved patient comfort/mobility; earlier discharge; and improved sustainability.ObjectivesTo measure baseline proportion of surgical patients meeting the criteria for oral receiving oral metronidazole; introduce tests of change to promote use of oral metronidazole where appropriate; and measure changes in prescribing behaviour to determine if improvement has been achieved, with the aim of increasing the proportion of oral metronidazole prescribed to eligible Royal Alexandra Hospital (RAH) surgical patients to 50% by February 2022.MethodsBaseline metronidazole prescribing data were collected over 6 weeks in surgical wards at the RAH. Exclusions for oral metronidazole included compromised gut absorption, oral route unreliable or worsening clinical condition/sepsis. A quality improvement approach was used to engage and raise awareness of the multidisciplinary surgical team to the benefits of prescribing oral metronidazole where appropriate. A range of methods were used including prospective audit and feedback; departmental presentations to surgical and pharmacy teams; eye-catching posters in key areas; staff champions; staff recognition awards; WhatsApp© group messages; and West of Scotland Surgical Association presentation. To measure improvement the proportion of oral and IV metronidazole prescribed was measured weekly and oral and IV metronidazole usage data in RAH surgical wards was measured monthly. A questionnaire was used to assess the impact of the project on nursing staff.ResultsBaseline data (n = 90) highlighted that only 13.5% of patients meeting the criteria for oral metronidazole were prescribed oral in RAH surgical wards. Post-change: oral metronidazole prescribing increased from a baseline median of 7% to 51%; IV metronidazole usage data decreased by 45%; there were 320 fewer IV metronidazole administrations per month; and nursing staff reported benefits including reduced workload, improved patient comfort and reduced plastic waste.ConclusionsA quality improvement approach to engage and raise staff awareness of the benefits of oral metronidazole resulted in a change in prescribing behaviour and increased the proportion of oral metronidazole prescribed to eligible surgical patients to 50% by February 2022.

SP7.1.3 An integrated and upgraded meta-analysis of published randomized, controlled trials exploring the role of oral metronidazole as post-operative proctological analgesic agent

Abstract Aims Proctological procedures such as haemorrhoidectomy have been reported with significant post-operative pain affecting quality of life as well as capacity to perform daily activities. The objective of this article is to explore the role of conventionally used antibiotic metronidazole as a proctological analgesic. Methods A systematic review of the randomized, controlled trials reporting the use of oral metronidazole as post-operative proctological analgesic agent in patients undergoing haemorrhoidectomy published on Embase, Medline, PubMed, PubMed Central and Cochrane databases was performed using the principles of meta-analysis. Results A total of eight randomized, controlled trials on 447 patients were included in this study. In the random effects model analysis using the statistical software Review Manager, the use of oral metronidazole as a post-operative proctological analgesic agent was significantly associated with the reduced pain score on day 1 (Standardized mean difference (SMD), -0.56; 95% CI, -1.04, -0.07; z = 2.26; P = 0.02), day 3 (SMD, -0.82; 95% CI, -1.33, -0.31; z = 3.15; P = 0.002) and day 7 (SMD, -1.48; 95% CI, -2.51, -0.45; z = 2.82; P = 0.005). There was significant heterogeneity (Tau2 = 0.39, chi2 = 38.38, df = 7, [p = 0.00001]; I2 = 82 %) among included studies. Conclusion The use of oral metronidazole as a post-operative proctological analgesic agent following haemorrhoidectomy seems to have proven clinical advantages and may routinely be used.

Improving metronidazole prescription practices in surgical patients: a full cycle audit

IntroductionMetronidazole is commonly prescribed for intra-abdominal infections. Oral metronidazole has high bioavailability (>95%) and intravenous metronidazole should be reserved for patients not suitable for oral preparations.Methods and materialsThis full cycle...

Intermittent Lactobacilli-containing Vaginal Probiotic or Metronidazole Use to Prevent Bacterial Vaginosis Recurrence: A Pilot Study Incorporating Microscopy and Sequencing

Bacterial vaginosis (BV) is associated with HIV acquisition and adverse pregnancy outcomes. Recurrence after metronidazole treatment is high. HIV-negative, non-pregnant Rwandan BV patients were randomized to four groups (n = 17/group) after seven-day oral metronidazole treatment: behavioral counseling only (control), or counseling plus intermittent use of oral metronidazole, Ecologic Femi+ vaginal capsule (containing multiple Lactobacillus and one Bifidobacterium species), or Gynophilus LP vaginal tablet (L. rhamnosus 35) for two months. Vaginal microbiota assessments at all visits included Gram stain Nugent scoring and 16S rRNA gene qPCR and HiSeq sequencing. All interventions were safe. BV (Nugent 7–10) incidence was 10.18 per person-year at risk in the control group, and lower in the metronidazole (1.41/person-year; p = 0.004), Ecologic Femi+ (3.58/person-year; p = 0.043), and Gynophilus LP groups (5.36/person-year; p = 0.220). In mixed effects models adjusted for hormonal contraception/pregnancy, sexual risk-taking, and age, metronidazole and Ecologic Femi+ users, each compared to controls, had higher Lactobacillus and lower BV-anaerobes estimated concentrations and/or relative abundances, and were less likely to have a dysbiotic vaginal microbiota type by sequencing. Inter-individual variability was high and effects disappeared soon after intervention cessation. Lactobacilli-based vaginal probiotics warrant further evaluation because, in contrast to antibiotics, they are not expected to negatively affect gut microbiota or cause antimicrobial resistance.

Treatment of bacterial vaginosis before 28weeks of pregnancy to reduce the incidence of preterm labor.

Controversy exists regarding the benefits of treating bacterial vaginosis (BV) during pregnancy to reduce the incidence of preterm labor (PTL). To evaluate whether treatment of BV with vaginal clindamycin or oral metronidazole before 28weeks of pregnancy reduces PTL incidence. PubMed, Scopus, Web of Science, Science Direct, CENTRAL, and SciELO databases were searched until December 30, 2017. Search terms included "bacterial vaginosis" and "preterm labor." No language restrictions were applied. Randomized clinical trials that evaluated treatment of BV with clindamycin or metronidazole to reduce PTL incidence. The risk of PTL was evaluated by the odds ratio (OR) and 95% confidence interval (CI). Dichotomous data from each study were combined for meta-analysis using the Mantel-Haenszel model. Nine reports were included in the systematic review, with eight reports included in the meta-analysis. No reduction in the incidence of PTL was found for either metronidazole (OR 0.94, 95% CI 0.71-1.25) or clindamycin (OR 1.01, 95% CI 0.75-1.36). Use of oral metronidazole or vaginal clindamycin to treat BV before 28weeks of pregnancy did not reduce the incidence of PTL. PROSPERO registration: CRD42018086173.

The Impact of Diagnostic Stewardship on Clostridium difficile Infections

Background Clostridium difficile infections (CDI) pose a growing threat to hospitalized patients. This study assesses the impact of changing from a nucleic acid amplification test (NAAT) to a stepwise testing algorithm (STA) by using an enzyme immunoassay (GDH and toxin A/B) and confirmatory NAAT confirmation in specific cases.MethodsIn an 885 bed academic medical center a 24 month pre-/post design was used to assess the effect of the STA for the following parameters: rates of enterocolitis due to C.diff (CDE), NHSN C.diff LabID events, CDI complications, mortality, antimicrobial prescription patterns, cluster occurrences; and testing, treatment, and isolation costs. Inpatient data were extracted from ICD-9/10 diagnosis codes, infection prevention, and laboratory databases.ResultsThe STA significantly decreased the number of CDE ICD9/10 codes, HO, CO, and CO-HCFA C.diff LabID event rates by 65%, 78%, 75%, and 75%, respectively. Similar reductions were noted for associated complications such as NHSN defined colon surgeries (-61%), megacolon (-64%), and acute kidney failure (-55%). CDE unrelated complication rates for colon surgeries and acute kidney failure remained constant while the diagnosis of megacolon decreased but not significantly (-71%; P > 0.05). Inpatient mortality did not change with or without CDE. Significant reductions were observed in the use of oral metronidazole (total: -32%; CDE specific: -70%) and vancomycin (total: -58%; CDE specific: -61%). There were no clusters detected pre-/post STA introduction. The need for isolation decreased from 748 to 181 patients post-intervention (-76%; P < 0.05). Annual cost savings were over $175,000 due to decreases in laboratory testing followed by isolation, and antibiotic use.ConclusionThe switch to an STA from NAAT did not affect the diagnosis, treatment, or control of clinically relevant CDI in our institution. Benefits included avoidance of unnecessary antibiotic treatment, reduction in isolation, achieving publicly reported objectives, and costs savings. Selection of clinically relevant tests can help to improve hospitalization and treatment of patients and should be considered as part of diagnostic stewardship.Disclosures All authors: No reported disclosures.

Chilean consensus of prevention, diagnosis and treatment of Clostridium difficile-associated diarrhea

Clostridium dijfficile-associated diarrhea (CDAD) has become very important due to the increase in its incidence, severity, recurrence and the associated economic burden. Having a national consensus guideline is essential to improve its management. To build a multidisciplinary and evidence-based consensus in prevention, diagnosis and treatment of CDAD. We convened a panel of experts in the field of infectious diseases, gastroenterology, evidence-based medicine and consensus methodology. The panel conducted a structured review of published literature in CDAD evaluating evidence levels and recommendation degree according to the methodology proposed by the GRADE working-group. A modified three-round Delphi technique was used to reach a consensus among the experts. A group of 16 experts was established, 12 of them answered 18 clinically relevant questions. The levels of agreement achieved by the panel of 16 experts were 79% in the first round and 100% in the second and third round. The main consensus recommendations in prevention are: restricting the use of proton-pump inhibitors, primary prophylaxis with probiotics in antibiotics users, education of health personnel, isolation for patients hospitalized with CDAD, and cleaning the rooms exposed to C. difficile with products based in chlorine or hydrogen peroxide. In the diagnosis: use of biology molecular-based techniques is preferred and if not available, glutamate dehydrogenase-based algorithms may be recommended. With regard to treatment: the use of oral metronidazole in mild-moderate CDAD and oral vancomycin in severe CDAD are recommended. Treat the first recurrence with the same antibiotics according to severity. In the case of second and subsequent recurrences consider prolonged therapy with vancomycin, rifaximin or fecal microbiota transplant. The first Chilean consensus on prevention, diagnosis and treatment of CDAD is presented, which is a major step in improving national standards in the management of this disease.

The use of metronidazole during pregnancy: a review of evidence.

To review the available evidence concerning the relationship between the exposure to metronidazole during pregnancy and the risk of preterm delivery and birth defects. Studies investigating the association between gestational use of oral metronidazole on human subjects and the risk of preterm birth or/and birth defects were systematically retrieved from MEDLINE and EMBASE databases. We selected studies published in English or French between 1964 and 2012. Where effect estimates were not reported, crude ORs along with 95% confidence intervals were calculated. We selected 17 studies investigating the association between exposure to oral metronidazole and the risk of preterm birth, from which 12 were randomized clinical trials. In addition, we identified 13 studies devoted to the relationship between metronidazole and birth defects, from which 10 were cohort studies, 1 was a case-control study and 2 were meta-analysis. During pregnancy, treating bacterial vaginosis and trichomoniasis with metronidazole is effective and offers no teratogen risk. Benefit of metronidazole in the reduction of preterm birth was demonstrated for the combination of this medication with other antibiotics. Additional information is needed when metronidazole is used in association with other agents.

ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile-associated disease.

ASHP supports preferential use of oral metronidazole for treating CDAD when antimicrobial therapy is indicated. Oral vancomycin should be reserved for severe, potentially life-threatening cases or when oral metronidazole cannot be used. Oral metronidazole is as safe and effective as oral vancomycin and is considerably less costly. In addition, preliminary data suggest that routine use of oral vancomycin for CDAD may contribute to the spread of VRE--emerging nosocomial pathogens that can be extraordinarily difficult to treat. Pharmacists should work to foster preferential prescribing of oral metronidazole for the treatment of CDAD. Pharmacists should also actively seek opportunities to educate health care providers and counsel patients about the risks associated with the indiscriminate use of vancomycin and other antimicrobial agents.

Clostridium difficile infection.

The spore-forming anaerobe Clostridium difficile has become a serious enteropathogen. Changes in the composition of natural intestinal flora, mainly due to antibiotic therapy, permit its colonization of, and multiplication in, the colon. The disease is caused by (entero)toxin A and (cyto)toxin B, and infection ranges from asymptomatic carrier state and mild diarrhea to pseudomembranous colitis. The clinical diagnosis is made by observing inflammatory, sometimes bloody, diarrhea and by the colonoscopic detection of epithelial necrosis, ulceration, and, in the advanced state, pseudomembrane formation. The laboratory supports the diagnosis by detecting toxin A and/or B by an enzyme-linked immunoassay with high specificity, but sometimes less sensitivity than with the cytotoxin assay in tissue culture cells. Fecal leukocytes or fecal lactoferrin may be found. Culture for the isolation and identification of toxigenic C. difficile is time consuming but necessary for epidemiological studies. Polymerase chain reaction (PCR) tests have been tested for detection of the toxin B gene directly in stool. Therapy consists of stopping all systemic antibiotic treatment and the use of oral metronidazole or vancomycin. There may be more relapses after vancomycin therapy, and the increasing vancomycin resistance of Enterococcus is worrisome. Prevention, especially of nosocomial spread, requires isolation and enforced handwashing. For epidemiological studies, the bacteria can be typed by molecular DNA analyses, including PCR, protein electrophoresis, and immunological tests.

Use of oral metronidazole in pregnancy: Risks, benefits, and practice guidelines

Metronidazole is the recommended treatment for trichomoniasis and bacterial vaginosis in nonpregnant women. Reluctance to use this drug in pregnancy is related to concerns about possible adverse effects on the fetus. However, recent literature suggests associations between these infections during pregnancy and risk of preterm delivery; if such associations are causal and preterm birth is shown to be prevented by effective treatment, the risk-benefit equation may be altered. This article reviews the literature on the carcinogenic and teratogenic potential of metronidazole and discusses the evidence that associates trichomoniasis and bacterial vaginosis with perinatal outcomes. Current practice recommendations are summarized.

Clostridium difficile Colitis

Clostridium difficile has become one of the commonest pathogens of the lower intestinal tract. This organism appears unique in that infection almost always occurs during or after antibiotic therapy, suggesting that some component of the normal microflora prevents colonization by C. difficile. Once it has overgrown in the colon, C. difficile releases several toxins which cause tissue damage and diarrhea. Infection can range from a simple self-limited diarrheal illness to fulminant colitis with perforation and megacolon. Assay of stool filtrates reveals the presence of cytotoxin in nearly all patients with antibiotic-associated pseudomembranous colitis, and in approximately one third to one half of those with less severe infections. Effective therapy is available in the form of oral vancomycin, although the expense of this antibiotic has led to the use of oral metronidazole or bacitracin, which appear to be equally efficacious and considerably cheaper. Although we have learned a great deal about C. difficile in the past decade, a number of fascinating puzzles remain. We know very little about the immune response to this organism or its toxin, or whether a vaccine might someday be feasible. Similarly, we have very little insight into what effects antibodies exert on the normal colonic flora and how these effects allow C. difficile infection in a small percentage of patients. Studies of this pathogen will undoubtedly lead to a fuller understanding of the enormously complex and still mysterious microbial ferment which lives within our gastrointestinal tract.

Multidisciplinary cost-containment program promoting oral metronidazole for treatment of antibiotic-associated colitis

A multidisciplinary cost-containment program for promoting oral metronidazole in place of oral vancomycin as initial therapy of antibiotic-associated colitis (AAC) is described. The pharmacy department and the division of infectious diseases implemented the program in two phases. In the first phase, a one-year retrospective drug-use review in patients with AAC treated with oral vancomycin was conducted to determine the average cost of therapy per treatment course. In the second phase, the use of oral metronidazole instead of oral vancomycin for initial treatment of AAC was promoted using inservice-education programs and distribution of pocket-size brochures containing AAC treatment guidelines to medical staff. The pharmacy and therapeutics committee supported the program by endorsing metronidazole as the drug of choice for AAC and by distributing follow-up progress reports of the program to medical staff. Pharmacists on the nursing units were responsible for enforcing the program stipulations regarding vancomycin and metronidazole use and for collecting data on patient-specific drug use. Six months after implementation of the program, the average cost of drug therapy for AAC had decreased by 89%, from $343.24 per patient to $37.50 per patient. The projected annual savings resulting from the program was $38,829.02. All prescribing physicians and dispensing pharmacists complied 100% with the program stipulations regarding drug use. The multidisciplinary program described here was successful in promoting the use of oral metronidazole for initial therapy of AAC.

Multicentre Study of ‘Flagyl’ in the Prevention of Post-Operative Anaerobic Infection

In a study carried out with 565 patients undergoing gynaecological and general surgical procedures, metronidazole ('Flagyl') was used pre- and post-operatively and the incidence of post-operative infection, particularly that due to anaerobic organisms, was recorded. This was not a controlled study but, by comparison with other series, it would appear that the use of oral metronidazole had substantially reduced the likelihood of supervention of anaerobic sepsis. It is probable that the use of intravenous metronidazole therapy would have reduced the incidence of anaerobic sepsis still further had this preparation been available at the time.