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The Journal of Antimicrobial... Dec 2022Clostridioides difficile infection (CDI) remains a significant clinical challenge both in the management of severe and severe-complicated disease and the prevention of... (Review)
Review
Clostridioides difficile infection (CDI) remains a significant clinical challenge both in the management of severe and severe-complicated disease and the prevention of recurrence. Guidelines released by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America (IDSA/SHEA) and ESCMID had some consensus as well as some discrepancies in disease severity classification and treatment recommendations. We review and compare the key clinical strategies from updated IDSA/SHEA, ESCMID and current Australasian guidelines for CDI management in adults and discuss relevant issues for clinicians, particularly in the management of severe-complicated infection. Updated IDSA/SHEA and ESCMID guidelines now reflect the increased efficacy of fidaxomicin in preventing recurrence and have both promoted fidaxomicin to first-line therapy with an initial CDI episode in both non-severe and severe disease and endorsed the role of bezlotoxumab in the prevention of recurrent infection. Vancomycin remains acceptable therapy and metronidazole is not preferred. For severe-complicated infection the IDSA/SHEA recommends high-dose oral ± rectal vancomycin and IV metronidazole, whilst in an important development, ESCMID has endorsed fidaxomicin and tigecycline as part of combination anti-CDI therapy, for the first time. The role of faecal microbiota transplantation (FMT) in second CDI recurrence is now clearer, but timing and mode of FMT in severe-complicated refractory disease still requires further study.
Topics: Adult; Humans; Vancomycin; Fidaxomicin; Metronidazole; Clostridioides difficile; Clostridium Infections; Anti-Bacterial Agents
PubMed: 36441203
DOI: 10.1093/jac/dkac404 -
Clinical Infectious Diseases : An... Jun 2021Case reports have described instances of peripheral and central nervous system toxicity during treatment with metronidazole; however, no large-scale studies have...
BACKGROUND
Case reports have described instances of peripheral and central nervous system toxicity during treatment with metronidazole; however, no large-scale studies have examined this association.
METHODS
We conducted a population-based nested case-control study of adults aged 66 years or older living in Ontario, Canada, between 1 April 2003 and 31 March 2017. Cases were individuals who attended hospital for any of cerebellar dysfunction, encephalopathy, or peripheral neuropathy within 100 days of a prescription for either metronidazole or clindamycin. We matched each case patient with up to 10 event-free control subjects who also received metronidazole or clindamycin. We used conditional logistic regression to test the association between metronidazole exposure and neurologic events, with clindamycin as the reference exposure.
RESULTS
We identified 1212 cases with recent use of either metronidazole or clindamycin and 12 098 controls. Neurologic adverse events were associated with an increased odds of metronidazole exposure compared to clindamycin (odds ratio [OR], 1.72 [95% confidence interval {CI}, 1.53-1.94]), which persisted after accounting for patient demographics, comorbidities, and other medication exposures (adjusted odds ratio [aOR], 1.43 [95% CI, 1.26-1.63]). We found a consistent association limited to either central (aOR, 1.46 [95% CI, 1.27-1.68]) or peripheral (aOR, 1.34 [95% CI, 1.02-1.76]) nervous system events. Among metronidazole recipients, the overall incidence of neurologic events at 100 days was approximately 0.25%.
CONCLUSIONS
Metronidazole is associated with an increased risk of adverse peripheral and central nervous system events relative to clindamycin. Clinicians and patients should be aware of these rare but potentially serious adverse events.
Topics: Adult; Case-Control Studies; Clindamycin; Humans; Metronidazole; Odds Ratio; Ontario
PubMed: 32303736
DOI: 10.1093/cid/ciaa395 -
American Family Physician Aug 2015Rosacea is a chronic facial skin condition of unknown cause. It is characterized by marked involvement of the central face with transient or persistent erythema,...
Rosacea is a chronic facial skin condition of unknown cause. It is characterized by marked involvement of the central face with transient or persistent erythema, telangiectasia, inflammatory papules and pustules, or hyperplasia of the connective tissue. Transient erythema, or flushing, is often accompanied by a feeling of warmth. It usually lasts for less than five minutes and may spread to the neck and chest. Less common findings include erythematous plaques, scaling, edema, phymatous changes (thickening of skin due to hyperplasia of sebaceous glands), and ocular symptoms. The National Rosacea Society Expert Committee defines four subtypes of rosacea (erythematotelangiectatic, papulopustular, phymatous, and ocular) and one variant (granulomatous). Treatment starts with avoidance of triggers and use of mild cleansing agents and moisturizing regimens, as well as photoprotection with wide-brimmed hats and broad-spectrum sunscreens (minimum sun protection factor of 30). For inflammatory lesions and erythema, the recommended initial treatments are topical metronidazole or azelaic acid. Once-daily brimonidine, a topical alpha-adrenergic receptor agonist, is effective in reducing erythema. Papulopustular rosacea can be treated with systemic therapy including tetracyclines, most commonly subantimicrobial-dose doxycycline. Phymatous rosacea is treated primarily with laser or light-based therapies. Ocular rosacea is managed with lid hygiene, topical cyclosporine, and topical or systemic antibiotics.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Dermatologic Agents; Education, Medical, Continuing; Female; Humans; Male; Metronidazole; Middle Aged; Phototherapy; Rosacea
PubMed: 26280139
DOI: No ID Found -
Journal of Veterinary Internal Medicine Sep 2020Metronidazole has a substantial impact on the gut microbiome. However, the recovery of the microbiome after discontinuation of administration, and the metabolic...
BACKGROUND
Metronidazole has a substantial impact on the gut microbiome. However, the recovery of the microbiome after discontinuation of administration, and the metabolic consequences of such alterations have not been investigated to date.
OBJECTIVES
To describe the impact of 14-day metronidazole administration, alone or in combination with a hydrolyzed protein diet, on fecal microbiome, metabolome, bile acids (BAs), and lactate production, and on serum metabolome in healthy dogs.
ANIMALS
Twenty-four healthy pet dogs.
METHODS
Prospective, nonrandomized controlled study. Dogs fed various commercial diets were divided in 3 groups: control group (no intervention, G1); group receiving hydrolyzed protein diet, followed by metronidazole administration (G2); and group receiving metronidazole only (G3). Microbiome composition was evaluated with sequencing of 16S rRNA genes and quantitative polymerase chain reaction (qPCR)-based dysbiosis index. Untargeted metabolomics analysis of fecal and serum samples was performed, followed by targeted assays for fecal BAs and lactate.
RESULTS
No changes were observed in G1, or G2 during diet change. Metronidazole significantly changed microbiome composition in G2 and G3, including decreases in richness (P < .001) and in key bacteria such as Fusobacteria (q < 0.001) that did not fully resolve 4 weeks after metronidazole discontinuation. Fecal dysbiosis index was significantly increased (P < .001). Those changes were accompanied by increased fecal total lactate (P < .001), and decreased secondary BAs deoxycholic acid and lithocholic acid (P < .001).
CONCLUSION AND CLINICAL IMPORTANCE
Our results indicate a minimum 4-week effect of metronidazole on fecal microbiome and metabolome, supporting a cautious approach to prescription of metronidazole in dogs.
Topics: Animals; Dogs; Feces; Metabolome; Metronidazole; Microbiota; Prospective Studies; RNA, Ribosomal, 16S
PubMed: 32856349
DOI: 10.1111/jvim.15871 -
Australian Family Physician 2017Rosacea is a chronic and common cutaneous condition characterised by symptoms of facial flushing and a broad spectrum of clinical signs. The clinical presentation for...
BACKGROUND
Rosacea is a chronic and common cutaneous condition characterised by symptoms of facial flushing and a broad spectrum of clinical signs. The clinical presentation for rosacea is varied, and there are four primary subtypes, which may overlap - erythrotelangiectatic, inflammatory, phymatous and ocular. It is important to recognise the different subtypes because of the differences in therapy.
OBJECTIVE
The objective of this article is to provide evidence-based clinical updates to clinicians, specifically general practitioners (GPs), to assist with their everyday practice, and effective assessment and treatment of rosacea.
DISCUSSION
Therapeutic modalities are chosen on the basis of the subtypes and clinical features identified; often a combination of these therapies is required.
Topics: Anti-Bacterial Agents; Brimonidine Tartrate; Diagnosis, Differential; Doxycycline; Humans; Isotretinoin; Ivermectin; Laser Therapy; Metronidazole; Rosacea
PubMed: 28472572
DOI: No ID Found -
Clinical Infectious Diseases : An... Apr 2021Anaerobic organisms are important pathogens in acute pelvic inflammatory disease (PID). The currently recommended PID regimen of a single dose of ceftriaxone and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Anaerobic organisms are important pathogens in acute pelvic inflammatory disease (PID). The currently recommended PID regimen of a single dose of ceftriaxone and doxycycline for 14 days has limited anaerobic activity. The need for broader anaerobic coverage is unknown and concerns have been raised about metronidazole tolerability.
METHODS
We conducted a randomized, double-blind, placebo-controlled trial comparing ceftriaxone 250 mg intramuscular single dose and doxycycline for 14 days, with or without 14 days of metronidazole in women with acute PID. The primary outcome was clinical improvement at 3 days following enrollment. Additional outcomes at 30 days following treatment were the presence of anaerobic organisms in the endometrium, clinical cure (absence of fever and reduction in tenderness), adherence, and tolerability.
RESULTS
We enrolled 233 women (116 to metronidazole and 117 to placebo). Clinical improvement at 3 days was similar between the 2 groups. At 30 days following treatment, anaerobic organisms were less frequently recovered from the endometrium in women treated with metronidazole than placebo (8% vs 21%, P < .05) and cervical Mycoplasma genitalium was reduced (4% vs 14%, P < .05). Pelvic tenderness was also less common among women receiving metronidazole (9% vs 20%, P < .05). Adverse events and adherence were similar in each treatment group.
CONCLUSIONS
In women treated for acute PID, the addition of metronidazole to ceftriaxone and doxycycline was well tolerated and resulted in reduced endometrial anaerobes, decreased M. genitalium, and reduced pelvic tenderness compared to ceftriaxone and doxycycline. Metronidazole should be routinely added to ceftriaxone and doxycycline for the treatment of women with acute PID.
CLINICAL TRIALS REGISTRATION
NCT01160640.
Topics: Anti-Bacterial Agents; Ceftriaxone; Doxycycline; Female; Humans; Metronidazole; Mycoplasma genitalium; Pelvic Inflammatory Disease
PubMed: 32052831
DOI: 10.1093/cid/ciaa101 -
Clinical Infectious Diseases : An... Jun 2016When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections.... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Ceftazidime-Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results From a Randomized, Controlled, Double-Blind, Phase 3 Program.
BACKGROUND
When combined with ceftazidime, the novel non-β-lactam β-lactamase inhibitor avibactam provides a carbapenem alternative against multidrug-resistant infections. Efficacy and safety of ceftazidime-avibactam plus metronidazole were compared with meropenem in 1066 men and women with complicated intra-abdominal infections from 2 identical, randomized, double-blind phase 3 studies (NCT01499290 and NCT01500239).
METHODS
The primary end point was clinical cure at test-of-cure visit 28-35 days after randomization, assessed by noninferiority of ceftazidime-avibactam plus metronidazole to meropenem in the microbiologically modified intention-to-treat (mMITT) population (in accordance with US Food and Drug Administration guidance), and the modified intention-to-treat and clinically evaluable populations (European Medicines Agency guidance). Noninferiority was considered met if the lower limit of the 95% confidence interval for between-group difference was greater than the prespecified noninferiority margin of -12.5%.
RESULTS
Ceftazidime-avibactam plus metronidazole was noninferior to meropenem across all primary analysis populations. Clinical cure rates with ceftazidime-avibactam plus metronidazole and meropenem, respectively, were as follows: mMITT population, 81.6% and 85.1% (between-group difference, -3.5%; 95% confidence interval -8.64 to 1.58); modified intention-to-treat, 82.5% and 84.9% (-2.4%; -6.90 to 2.10); and clinically evaluable, 91.7% and 92.5% (-0.8%; -4.61 to 2.89). The clinical cure rate with ceftazidime-avibactam plus metronidazole for ceftazidime-resistant infections was comparable to that with meropenem (mMITT population, 83.0% and 85.9%, respectively) and similar to the regimen's own efficacy against ceftazidime-susceptible infections (82.0%). Adverse events were similar between groups.
CONCLUSIONS
Ceftazidime-avibactam plus metronidazole was noninferior to meropenem in the treatment of complicated intra-abdominal infections. Efficacy was similar against infections caused by ceftazidime-susceptible and ceftazidime-resistant pathogens. The safety profile of ceftazidime-avibactam plus metronidazole was consistent with that previously observed with ceftazidime alone.
CLINICAL TRIALS REGISTRATION
NCT01499290 and NCT01500239.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Drug Combinations; Female; Humans; Intraabdominal Infections; Male; Meropenem; Metronidazole; Middle Aged; Thienamycins; Treatment Outcome; Young Adult
PubMed: 26962078
DOI: 10.1093/cid/ciw133 -
JAMA Sep 2017The rate of obesity among US women has been increasing, and obesity is associated with increased risk of surgical site infection (SSI) following cesarean delivery. The... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The rate of obesity among US women has been increasing, and obesity is associated with increased risk of surgical site infection (SSI) following cesarean delivery. The optimal perioperative antibiotic prophylactic regimen in this high-risk population undergoing cesarean delivery is unknown.
OBJECTIVE
To determine rates of SSI among obese women who receive prophylactic oral cephalexin and metronidazole vs placebo for 48 hours following cesarean delivery.
DESIGN, SETTING, AND PARTICIPANTS
Randomized, double-blind clinical trial comparing oral cephalexin and metronidazole vs placebo for 48 hours following cesarean delivery for the prevention of SSI in obese women (prepregnancy BMI ≥30) who had received standard intravenous preoperative cephalosporin prophylaxis. Randomization was stratified by intact vs rupture of membranes prior to delivery. The study was conducted at the University of Cincinnati Medical Center, Cincinnati, Ohio, an academic and urban setting, between October 2010 and December 2015, with final follow-up through February 2016.
INTERVENTIONS
Participants were randomly assigned to receive oral cephalexin, 500 mg, and metronidazole, 500 mg (n = 202 participants), vs identical-appearing placebo (n = 201 participants) every 8 hours for a total of 48 hours following cesarean delivery.
MAIN OUTCOMES AND MEASURES
The primary outcome was SSI, defined as any superficial incisional, deep incisional, or organ/space infections within 30 days after cesarean delivery.
RESULTS
Among 403 randomized participants who were included (mean age, 28 [SD, 6] years; mean BMI, 39.7 [SD, 7.8]), 382 (94.6%) completed the trial. The overall rate of SSI was 10.9% (95% CI, 7.9%-14.0%). Surgical site infection was diagnosed in 13 women (6.4%) in the cephalexin-metronidazole group vs 31 women (15.4%) in the placebo group (difference, 9.0% [95% CI, 2.9%-15.0%]; relative risk, 0.41 [95% CI, 0.22-0.77]; P = .01). There were no serious adverse events, including allergic reaction, reported in either the antibiotic group or the placebo group.
CONCLUSIONS AND RELEVANCE
Among obese women undergoing cesarean delivery who received the standard preoperative cephalosporin prophylaxis, a postoperative 48-hour course of oral cephalexin and metronidazole, compared with placebo, reduced the rate of SSI within 30 days after delivery. For prevention of SSI among obese women after cesarean delivery, prophylactic oral cephalexin and metronidazole may be warranted.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT01194115.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Cephalexin; Cesarean Section; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Metronidazole; Obesity; Postoperative Care; Surgical Wound Infection
PubMed: 28975304
DOI: 10.1001/jama.2017.10567 -
Nature Microbiology Mar 2022Vaginal microbiota composition affects many facets of reproductive health. Lactobacillus iners-dominated microbial communities are associated with poorer outcomes,...
Vaginal microbiota composition affects many facets of reproductive health. Lactobacillus iners-dominated microbial communities are associated with poorer outcomes, including higher risk of bacterial vaginosis (BV), compared with vaginal microbiota rich in L. crispatus. Unfortunately, standard-of-care metronidazole therapy for BV typically results in dominance of L. iners, probably contributing to post-treatment relapse. Here we generate an L. iners isolate collection comprising 34 previously unreported isolates from 14 South African women with and without BV and 4 previously unreported isolates from 3 US women. We also report an associated genome catalogue comprising 1,218 vaginal Lactobacillus isolate genomes and metagenome-assembled genomes from >300 women across 4 continents. We show that, unlike L. crispatus, L. iners growth is dependent on L-cysteine in vitro and we trace this phenotype to the absence of canonical cysteine biosynthesis pathways and a restricted repertoire of cysteine-related transport mechanisms. We further show that cysteine concentrations in cervicovaginal lavage samples correlate with Lactobacillus abundance in vivo and that cystine uptake inhibitors selectively inhibit L. iners growth in vitro. Combining an inhibitor with metronidazole promotes L. crispatus dominance of defined BV-like communities in vitro by suppressing L. iners growth. Our findings enable a better understanding of L. iners biology and suggest candidate treatments to modulate the vaginal microbiota to improve reproductive health for women globally.
Topics: Cysteine; Female; Humans; Lactobacillus; Male; Metronidazole; Microbiota; Vagina; Vaginosis, Bacterial
PubMed: 35241796
DOI: 10.1038/s41564-022-01070-7 -
Dental and Medical Problems 2018Traditional methods of non-surgical treatment of periodontitis, including mechanical scaling/root planing (SRP), do not guarantee remission of the disease. Local... (Review)
Review
Traditional methods of non-surgical treatment of periodontitis, including mechanical scaling/root planing (SRP), do not guarantee remission of the disease. Local delivery of antimicrobial agents in periodontitis entails antimicrobial therapy placed directly in periodontal pockets. The advantage of this form of treatment is that the concentration of the drug after application significantly exceeds the minimum inhibitory concentration (MIC) and persists for up to several weeks. Therefore, many systems of locally applied devices, using a variety of antibiotics or antiseptics have been developed. There is continuous research aimed at introducing new forms of locally administered drugs, some of which have not proved to be effective, while others are promising. For almost 30 years such systems have been used for treatment as an adjuvant to SRP, and their efficacy has been evaluated. The aim of this article is to systematically review the contemporary literature regarding the currently available chemotherapeutics locally administered in the treatment of periodontitis.
Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Chlorhexidine; Drug Delivery Systems; Humans; Metronidazole; Periodontitis; Tetracycline
PubMed: 30328312
DOI: 10.17219/dmp/94890