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Journal of Animal Science Jan 2023In recent dog and cat experiments, a novel milk oligosaccharide biosimilar (GNU100) positively modulated fecal microbiota and metabolite profiles, suggesting benefits to...
Effects of a milk oligosaccharide biosimilar on fecal characteristics, microbiota, and bile acid, calprotectin, and immunoglobulin concentrations of healthy adult dogs treated with metronidazole.
In recent dog and cat experiments, a novel milk oligosaccharide biosimilar (GNU100) positively modulated fecal microbiota and metabolite profiles, suggesting benefits to gastrointestinal health. The objective of this study was to investigate the effects of GNU100 on the fecal characteristics, microbiota, and bile acid (BA) concentrations of healthy adult dogs treated with antibiotics. Twelve healthy adult female dogs (mean age: 3.74 ± 2.4 yr) were used in an 8-wk crossover design study (dogs underwent both treatments). All dogs were fed a control diet during a 2-wk baseline, then randomly allotted to 1 of 2 treatments (diet only or diet + 1% GNU100) for another 6 wk. From weeks 2 to 4, dogs were orally administered metronidazole (20 mg/kg BW) twice daily. Fecal scores were recorded daily and fresh fecal samples were collected at weeks 2, 4, 5, 6, and 8 for measurement of pH, dry matter, microbiota populations, and BA, immunoglobulin A, and calprotectin concentrations. On weeks 0, 4, and 8, blood samples were collected for serum chemistry and hematology analysis. All data were analyzed as repeated measures using the Mixed Models procedure of SAS version 9.4, with significance considered P < 0.05. Metronidazole increased (P < 0.0001) fecal scores (looser stools) and modified (P < 0.05) fecal microbiota and BA profiles. Using qPCR, metronidazole reduced fecal Blautia, Fusobacterium, Turicibacter, Clostridium hiranonis, and Faecalibacterium abundances, and increased fecal Streptococcus and Escherichia coli abundances. DNA sequencing analysis demonstrated that metronidazole reduced microbial alpha diversity and influenced the relative abundance of 20 bacterial genera and families. Metronidazole also increased primary BA and reduced secondary BA concentrations. Most antibiotic-induced changes returned to baseline by week 8. Fecal scores were more stable (P = 0.01) in GNU100-fed dogs than controls after antibiotic administration. GNU100 also influenced fecal microbiota and BA profiles, reducing (P < 0.05) the influence of metronidazole on microbial alpha diversity and returning some fecal microbiota and secondary BA to baseline levels at a quicker (P < 0.05) rate than controls. In conclusion, our results suggest that GNU100 supplementation provides benefits to dogs treated with antibiotics, providing more stable fecal scores, maintaining microbial diversity, and allowing for quicker recovery of microbiota and secondary BA profiles which play an essential role in gut health.
Topics: Dogs; Female; Animals; Cats; Metronidazole; Biosimilar Pharmaceuticals; Bile Acids and Salts; Milk; Leukocyte L1 Antigen Complex; Cat Diseases; Gastrointestinal Microbiome; Dog Diseases; Feces; Microbiota; Anti-Bacterial Agents; Immunoglobulins; Oligosaccharides; Animal Feed
PubMed: 36617268
DOI: 10.1093/jas/skad011 -
Sultan Qaboos University Medical Journal Feb 2022
Topics: Humans; Metronidazole; Radiography
PubMed: 35299800
DOI: 10.18295/squmj.5.2021.080 -
The Pediatric Infectious Disease Journal Jan 2023Infants frequently receive metronidazole at variable doses and duration for surgical site infection prophylaxis and treatment of intra-abdominal infections. Seizures are...
Exposure-response Relationships of Metronidazole in Infants: Integration of Electronic Health Record Data With Population Pharmacokinetic Modeling-derived Exposure Simulation.
BACKGROUND
Infants frequently receive metronidazole at variable doses and duration for surgical site infection prophylaxis and treatment of intra-abdominal infections. Seizures are a rare (but potentially devastating) side effect of metronidazole, yet the prevalence of seizures in infants, as well as the relationship with metronidazole dose and exposure, are unknown.
METHODS
We examined the Pediatrix Clinical Data Warehouse for infants in neonatal intensive care units from 1997 to 2018 who received at least 1 dose of metronidazole during their first 120 days of life. We used an existing population pharmacokinetic model to simulate exposure parameters, estimating multivariable associations between metronidazole dosing and exposure parameters, and the occurrence of seizure.
RESULTS
There were 19,367 intravenous doses of metronidazole given to 1546 infants, and 31 experienced a seizure. Infants with a seizure had a longer median (interquartile values) duration of metronidazole exposure than those without (11 days [6, 15] vs. 7 [4, 11], P = 0.01). Each added day of metronidazole (OR = 1.06, 95% CI: 1.02-1.10), and each standard deviation increase in cumulative area under the plasma concentration-time curve (OR = 1.27, 95% CI: 1.11-1.45) were associated with increased odds of seizure. Higher simulated maximum plasma concentration was associated with lower odds of seizure (OR = 0.88, 95% CI: 0.81-0.96).
CONCLUSIONS
Longer metronidazole exposure and higher cumulative exposure could be associated with increased odds of infant seizures. Using a large observational dataset allowed us to identify a rare adverse event, but prospective studies are needed to validate this finding and further characterize metronidazole dose- and exposure-safety relationships.
Topics: Infant, Newborn; Humans; Metronidazole; Electronic Health Records
PubMed: 36201670
DOI: 10.1097/INF.0000000000003726 -
Neurologia 2020
Topics: Anti-Infective Agents; Humans; Metronidazole; Neurotoxicity Syndromes
PubMed: 31780322
DOI: 10.1016/j.nrl.2019.08.001 -
Journal of Chemical Information and... Aug 2023Our skin constitutes an effective permeability barrier that protects the body from exogenous substances but concomitantly severely limits the number of pharmaceutical...
Our skin constitutes an effective permeability barrier that protects the body from exogenous substances but concomitantly severely limits the number of pharmaceutical drugs that can be delivered transdermally. In topical formulation design, chemical permeation enhancers (PEs) are used to increase drug skin permeability. skin permeability experiments can measure net effects of PEs on transdermal drug transport, but they cannot explain the molecular mechanisms of interactions between drugs, permeation enhancers, and skin structure, which limits the possibility to rationally design better new drug formulations. Here we investigate the effect of the PEs water, lauric acid, geraniol, stearic acid, thymol, ethanol, oleic acid, and eucalyptol on the transdermal transport of metronidazole, caffeine, and naproxen. We use atomistic molecular dynamics (MD) simulations in combination with developed molecular models to calculate the free energy difference between 11 PE-containing formulations and the skin's barrier structure. We then utilize the results to calculate the final concentration of PEs in skin. We obtain an RMSE of 0.58 log units for calculated partition coefficients from water into the barrier structure. We then use the modified PE-containing barrier structure to calculate the PEs' permeability enhancement ratios (ERs) on transdermal metronidazole, caffeine, and naproxen transport and compare with the results obtained from experiments. We show that MD simulations are able to reproduce rankings based on ERs. However, strict quantitative correlation with experimental data needs further refinement, which is complicated by significant deviations between different measurements. Finally, we propose a model for how to use calculations of the potential of mean force of drugs across the skin's barrier structure in a topical formulation design.
Topics: Molecular Dynamics Simulation; Skin Absorption; Naproxen; Caffeine; Metronidazole; Skin; Water; Permeability
PubMed: 37462219
DOI: 10.1021/acs.jcim.3c00625 -
Antimicrobial Agents and Chemotherapy Jul 2022Metronidazole (Met) is the first choice for treating Helicobacter pylori (). However, is easy to resistant, making Met unable to be widely used. How to overcome 's Met...
Metronidazole (Met) is the first choice for treating Helicobacter pylori (). However, is easy to resistant, making Met unable to be widely used. How to overcome 's Met resistance is still an issue. In this study, Met was used as the primary raw material with linolenic acid to prepare a novel compound-linolenic acid-metronidazole (Lla-Met). The MIC, minimum bactericidal concentration (MBC), colonization amount of in gastric mucosa, etc., were evaluated, respectively. Lla-Met was successfully prepared by the detection of nuclear magnetic resonance, etc., and its MIC and MBC to were 2~4 μg/mL, 8~16 μg/mL. Moreover, experiments, Lla-Met significantly reduced the colonization of drug-resistant in gastric mucosa. In the toxicity test, Lla-Met inhibited rate to GES-1 and BGC823 cells were 15% at 128 μg/mL; the mice were administered 10 times treatment Lla-Met treatment (240 mg/kg), have no difference significant injuries were found in their stomach, liver, spleen, kidney, and weight. In addition, G27 continued for 18 days with sub-Lla-Met concentration, G27 did not show drug resistance to Lla-Met; Lla-Met did not exert an effect on non- species with 128 μg/mL; Compared with a neutral environment, when the acid concentration is 3.0, Lla-Met is not decomposed and has better stability. Conclusion: Lla-Met, a newly prepared compound, has relatively well antibacterial of Met-resistant and sensitive , with a capability of overcoming the metronidazole resistance of
Topics: Animals; Anti-Bacterial Agents; Clarithromycin; Drug Resistance; Helicobacter Infections; Helicobacter pylori; Metronidazole; Mice; alpha-Linolenic Acid
PubMed: 35758720
DOI: 10.1128/aac.00073-22 -
Frontiers in Cellular and Infection... 2023Peri-implant diseases are pathological conditions that affect the survival of dental implants. Etiological studies are limited, accepting a prevalence of 20% at the... (Meta-Analysis)
Meta-Analysis Review
Peri-implant diseases are pathological conditions that affect the survival of dental implants. Etiological studies are limited, accepting a prevalence of 20% at the implant level and 24% at the patient level. The benefits of adjuvant metronidazole are controversial. A systematic review and meta-analysis of RCTs according to PRISMA and PICOS was performed with an electronic search over the last 10 years in MEDLINE (PubMed), WOS, Embase, and Cochrane Library. The risk of bias was measured using the Cochrane Risk of Bias tool and the methodological quality using the Jadad scale. Meta-analysis was performed with RevMan version 5.4.1, based on mean difference and standard deviation, with 95% confidence intervals; the random-effects model was selected, and the threshold for statistical significance was defined as < 0.05. A total of 38 studies were collected and five were selected. Finally, one of the studies was eliminated because of unanalyzable results. All studies reached a high methodological quality. A total of 289 patients were studied with follow-up periods from 2 weeks to 1 year. Statistical significance was only found, with respect to the use of adjunctive metronidazole, in the pooled analysis of the studies ( = 0.02) and in the analysis of the radiographic values reported on peri-implant marginal bone levels, in the studies with a 3-month follow-up ( = 0.03). Discrepancies in the use of systemic metronidazole require long-term randomized clinical trials (RCTs) to determine the role of antibiotics in the treatment of peri-implantitis.
Topics: Humans; Peri-Implantitis; Metronidazole; Anti-Bacterial Agents; Combined Modality Therapy; Bias
PubMed: 37287463
DOI: 10.3389/fcimb.2023.1149055 -
Tropical Medicine & International... Jan 1997To assess the efficacy of treatment of parasitological excretion of cysts and trophozoites and symptoms of patients with giardiasis, a systematic review of published... (Review)
Review
To assess the efficacy of treatment of parasitological excretion of cysts and trophozoites and symptoms of patients with giardiasis, a systematic review of published randomized clinical trials was conducted through extensive searches in Medline, Embase and Current Contents from 1966 till 1996 as well as manual reviews of 28 journals. The methodological quality of all trials was assessed by guidelines of the Cochrane Collaboration. Thirty-one trials were included, only one of which had no serious methodological flaws. The mean score of parasitological examination was 4.8 out of a possible 15. There was a considerable effect in cure rate of treatment versus placebo (odds 9.3, 95% CI 4.69-18.4), but all 3 trials in this comparison had serious flaws. Metronidazole treatment over more than 3 days seems to achieve a better parasitological cure rate than other long treatment courses (pooled odds 2.6, 95% 1.7-3.8), but trials are clinically and statistically heterogeneous. Single-dose therapy is as effective as longer treatment courses (pooled odds 0.67, 95% 0.31-1.44). Within the single-dose regimens tinidazole (2 g) reaches a higher parasitological cure rate than other short therapies (pooled odds 55, 95% CI 3.7-8.3) with relatively few side-effects. Placebo-controlled trials with parasitological and clinical outcomes are needed.
Topics: Antiprotozoal Agents; Giardiasis; Humans; Metronidazole; Randomized Controlled Trials as Topic; Tinidazole
PubMed: 9018304
DOI: 10.1046/j.1365-3156.1997.d01-132.x -
Antimicrobial Agents and Chemotherapy May 2020Periodontitis as a biofilm-associated inflammatory disease is highly prevalent worldwide. It severely affects oral health and yet closely links to systemic diseases like...
Periodontitis as a biofilm-associated inflammatory disease is highly prevalent worldwide. It severely affects oral health and yet closely links to systemic diseases like diabetes and cardiovascular disease. as a "keystone" periodontopathogen drives the shift of microbe-host symbiosis to dysbiosis and critically contributes to the pathogenesis of periodontitis. Persisters represent a tiny subset of biofilm-associated microbes highly tolerant to lethal treatment of antimicrobials, and, notably, metronidazole-tolerant persisters have recently been identified by our group. This study further explored the interactive profiles of metronidazole-treated persisters (M-PgPs) with human gingival epithelial cells (HGECs). cells (ATCC 33277) at stationary phase were treated with a lethal dosage of metronidazole (100 μg/ml, 6 h) for generating M-PgPs. The interaction of M-PgPs with HGECs was assessed by microscopy, flow cytometry, cytokine profiling, and quantitative PCR (qPCR). We demonstrated that the overall morphology and ultracellular structure of M-PgPs remained unchanged. Importantly, M-PgPs maintained the capabilities to adhere to and invade HGECs. Moreover, M-PgPs significantly suppressed proinflammatory cytokine expression in HGECs at a level comparable to that seen with the untreated cells, through the thermosensitive components. The present report reveals that persisters induced by lethal treatment of antibiotics were able to maintain their capabilities to adhere to and invade human gingival epithelial cells and to perturb the innate host responses. Novel strategies and approaches need to be developed for tackling and favorably modulating the dysregulated immunoinflammatory responses for oral/periodontal health and general well-being.
Topics: Cells, Cultured; Epithelial Cells; Gingiva; Humans; Metronidazole; Periodontitis; Porphyromonas gingivalis
PubMed: 32205352
DOI: 10.1128/AAC.02529-19 -
Scientific Reports Sep 2021Imidazole has anti-inflammatory, antituberculotic, antimicrobial, antimycotic, antiviral, and antitumor properties in the human body, to name a few. Metronidazole...
Imidazole has anti-inflammatory, antituberculotic, antimicrobial, antimycotic, antiviral, and antitumor properties in the human body, to name a few. Metronidazole [1-(2-Hydroxyethyl)-2-methyl-5-nitroimidazole] is a widely used antiprotozoan and antibacterial medication. Using fourier transform infrared spectroscopy, the current study models the antibacterial activity of already synthesised Metronidazole (MTZ) complexes ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]) against E. coli, B. bronceptica, S. epidermidis, B. pumilus and S. aureus. To characterise the Metronidazole complexes for antibacterial activity against 05 microbes, the least angular regression and least absolute shrinkage selection operators were used. Asymmetric Least Squares was used to correct the spectrum baseline. Least angular regression outperforms cross-validated root mean square error in the fitted models. Using Least angular regression, influential wavelengths that explain the variation in antibacterial activity of Metronidazole complexes were identified and mapped against functional groups.
Topics: Anti-Bacterial Agents; Bacillus pumilus; Bordetella bronchiseptica; Chemistry, Pharmaceutical; Escherichia coli; Metronidazole; Models, Chemical; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; Staphylococcus epidermidis
PubMed: 34588489
DOI: 10.1038/s41598-021-97897-x