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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 -
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 -
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 -
Antimicrobial Agents and Chemotherapy Feb 1976Urine from patients receiving metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitromidazole] orally or per vagina were subjected to paper chromatographic fractionation and...
Urine from patients receiving metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitromidazole] orally or per vagina were subjected to paper chromatographic fractionation and examined for anticlostridial activity. Unmodified metronidazole and several metabolites were detected. These findings indicate that the clostridial bioassay may be limited in its applicability to the study of the pharmacodynamics of metronidazole as it does not differentiate between the parent substance and some of its metabolites. Moreover, some of the latter, although they possess antibacterial activity, may not have antiprotozoan activity.
Topics: Biological Assay; Chromatography, Paper; Clostridium perfringens; Female; Humans; Metronidazole
PubMed: 178274
DOI: 10.1128/AAC.9.2.260 -
CMAJ : Canadian Medical Association... Oct 2021
Topics: Anti-Infective Agents; Humans; Metronidazole; Neurotoxicity Syndromes; Peripheral Nervous System Diseases
PubMed: 34697097
DOI: 10.1503/cmaj.201671 -
Sexual Medicine Reviews Apr 2022Secnidazole (SEC), newly FDA-approved for trichomoniasis, is a potent 5-nitroimidazole with selective toxicity against various infections. It has been used... (Review)
Review
INTRODUCTION
Secnidazole (SEC), newly FDA-approved for trichomoniasis, is a potent 5-nitroimidazole with selective toxicity against various infections. It has been used internationally to treat trichomoniasis, bacterial vaginosis, and other infections for decades. Trichomoniasis is the most common non-viral sexually transmitted infection worldwide and is associated with significant morbidity. In comparison to the only other approved treatments for trichomoniasis in the U.S.-metronidazole and tinidazole-SEC has favorable pharmacokinetics, including a longer half-life, and a lower minimal lethal concentration against Trichomonas vaginalis.
OBJECTIVES
Provide an updated, comprehensive review of the literature evaluating SEC as a treatment for trichomoniasis in women and men.
METHODS
We conducted a search to identify existing research on SEC and trichomoniasis. On August 6, 2021, we searched MEDLINE using the terms "secnidazole" and "trichomon.*" We excluded reviews, editorials, case reports, and small case series.
RESULTS
We identified 29 articles; 14 of which were included: 5 reported in vitro pharmacologic data on SEC, 6 were observational studies, and 4 were controlled clinical trials (1 observational study also reported in vitro pharmacologic data). Six studies reported data on women only, 1 on men only, and 3 on women and men. These studies showed that SEC-as a single dose or 3-day course-had comparable efficacy to multi-dose metronidazole for treating trichomoniasis in women and men, was generally well tolerated by patients, and had a favorable pharmacokinetic profile. A single 2-g dose of SEC also led to a microbiologic cure rate of 92.2% in the first randomized, double-blind, placebo-controlled study of trichomonas-infected US-based women.
CONCLUSION
SEC is an efficacious and safe treatment for women and men with trichomoniasis. Single-dose administration makes it a favorable treatment option for patients, especially in cases where adherence to other multi-dose treatment regimens could be problematic. Christina A. Muzny and Olivia T. Van Gerwen. Secnidazole for Trichomoniasis in Women and Men. Sex Med Rev 2022;10:255-262.
Topics: Female; Humans; Male; Metronidazole; Observational Studies as Topic; Randomized Controlled Trials as Topic; Trichomonas Infections; Trichomonas vaginalis; Vaginosis, Bacterial
PubMed: 35153156
DOI: 10.1016/j.sxmr.2021.12.004 -
Neurology India Jan 2024
Topics: Humans; Metronidazole
PubMed: 38443042
DOI: 10.4103/neurol-india.Neurol-India-D-23-00690 -
Internal Medicine (Tokyo, Japan) Apr 2024
Topics: Humans; Metronidazole; Brain Diseases; Anti-Infective Agents; Magnetic Resonance Imaging
PubMed: 37558473
DOI: 10.2169/internalmedicine.2288-23 -
Neurology India 2011
Topics: Animals; Antiprotozoal Agents; Humans; Metronidazole; Neurotoxicity Syndromes
PubMed: 21339650
DOI: 10.4103/0028-3886.76848 -
Swiss Dental Journal 2017Non-surgical periodontal therapy is often performed as a combinational approach using supplemental systemic amoxicillin and metronidazole. Better clinical outcomes, less...
Non-surgical periodontal therapy is often performed as a combinational approach using supplemental systemic amoxicillin and metronidazole. Better clinical outcomes, less need for periodontal surgery and limited systemic complications are arguments to justify such an approach. However, combination therapy with systemic antibiotic treatment is still a matter of debate due to emerging antibiotic resistance patterns. In this case report, a 61-year-old women suffering from an acute pancreatitis following systemic antibiotic combinational treatment as part of a non-surgical periodontal therapy is described. Following adequate symptomatic treatment during a hospitalization of three days, the patient recovered and periodontal conditions improved significantly thereafter. This case report illustrates a rare, but potentially serious complication when prescribing systemic combinational antibiotics in non-surgical periodontal therapy. Adequate history taking and timely diagnosis of pancreatitis if developing is important to provide relevant treatment and to avoid pancreatitis-associated complications.
Topics: Amoxicillin; Biofilms; Combined Modality Therapy; Dental Scaling; Female; Humans; Metronidazole; Middle Aged; Pancreatitis, Acute Necrotizing; Periodontitis; Referral and Consultation
PubMed: 28480950
DOI: No ID Found