Search Results (14)

Background and Aims: Ornidazole, a nitroimidazole antibiotic, is widely used for protozoal and anaerobic infections and is generally considered safe. However, ornidazole-induced liver injury (OILI) is an underrecognized yet potentially severe adverse reaction. This multicenter study aims to characterize the clinical features, histopathology, and outcomes of OILI to improve the awareness and management of this rare entity worldwide. Methods: We conducted a retrospective analysis of 101 patients with OILI from eight tertiary centers between 2006 and 2023. Cases were included based on liver enzyme elevations temporally linked to ornidazole and the exclusion of other causes. Causality was assessed using the Roussel Uclaf Causality Assessment Method (RUCAM) score. Clinical data, laboratory parameters, autoantibody profiles, histology, treatments, and outcomes were evaluated. Results: OILI was classified as highly probable in 42.6% of cases (n = 43), probable in 51.5% of cases (n = 52), and possible in 5.9% (n = 6) of cases. The predominant pattern was acute hepatocellular injury (83.2%) (n = 84). Autoimmune-like hepatitis occurred in 5% of cases (n = 5), with ANA positivity in 16.8% of cases (n = 17). Corticosteroids were used in 24.8% of cases (n = 25) and were associated with higher ANA positivity and a 20% (n = 5) relapse rate post-discontinuation. Recovery was achieved in 87.7% of cases (n = 88), while 7.9% of cases (n = 8) required liver transplantation and 4% (n = 4) died. Conclusions: Ornidazole can cause serious idiosyncratic liver injury, including autoimmune phenotypes, and should be considered in the differential diagnosis of acute hepatitis. Given the notable risk of liver failure and death, early recognition, drug discontinuation, and close monitoring are essential. In select cases, corticosteroids and plasmapheresis may be beneficial, though the evidence remains limited. Full article

Background: Antimicrobial resistance (AMR) is a public health concern worldwide, particularly in low-to-middle-income countries with few antimicrobial stewardship programs and few laboratories equipped for diagnosis. Methods: As point-prevalence surveys (PPSs) are a well-known tool for assessing antimicrobial use, we adjusted standardized Global-PPS for use in two hospitals in Benin and included an analysis based on the 2021 WHO AWaRe classification. Results: Of the 450 patients enrolled, 148 received antimicrobials (AMs) (overall prevalence 32.9%), most of them orally (54.2%). Both hospitals had a high rate of Access and Watch antibiotics use, and both prescribed mainly metronidazole. In four prescriptions, hospital A used a non-recommended association of antibiotics, such as ceftriaxone + sulbactam and ofloxacin + ornidazole. While hospital A prescribed predominantly amoxicillin + clavulanic acid (19/92; 21%) and ceftriaxone (14/92; 15%), hospital B prescribed ampicillin (24/120; 20%) and cefuroxime (14/120; n = 12%). In hospital B, surgical antimicrobial prophylaxis (SAP) was suboptimal. While there were no single-dose prophylaxis prescriptions, all one-day prophylaxis (SP2) involved ampicillin for cesarean sections. In patients in intensive care units, prolonged prophylaxis (>1 day, SP3) accounted for all postoperative prescriptions. Conclusions: These findings highlight the critical need for implementing antimicrobial stewardship programs, expanding diagnostic laboratory capacity to minimize empirical prescribing, and strengthening medical student training to ensure quality and rational antibiotic use, thereby addressing the growing challenge of resistance in resource-limited settings. Full article

Levornidazole, a nitroimidazole compound, has been linked to hepatotoxic adverse effects in clinical settings. However, the hepatotoxicity of levornidazole and its impurities has not been fully elucidated. This study aimed to predict and evaluate the potential hepatotoxicity of levornidazole, and elucidate the underlying mechanisms of action. Computational models based on support vector machines (SVM) and artificial neural networks (ANN) predicted that levornidazole, ornidazole, and impurity II exhibited hepatotoxic effects. The hepatotoxicity of levornidazole and impurity II was confirmed using a zebrafish toxicity study, with impurity II demonstrating hepatotoxicity at lower doses. Molecular structure analysis revealed that the electronegativity of the side-chain groups and the molecular polarity structure were correlated with the degree of hepatotoxicity. The toxic response was primarily associated with specific structural domains of the molecule, including the 2-methyl-5-nitro-1H-imiddaster-1-yl structure and the substituent groups of 1-chloro and 2(S)-2-methyloxirane. Transcriptome sequencing analysis indicated that levornidazole and impurity II affect multiple metabolic processes in the liver, including glucose, lipid, protein, hormone, and drug metabolism. These findings highlight the potential hepatotoxic risks associated with levomeprazole and its impurities, emphasizing the importance of further investigation and regulatory attention to ensure patient safety. Full article

A sensitive, easy-to-use, fast, and cost-effective TLC-densitometric method was developed for the separation of metronidazole, secnidazole, ornidazole, tinidazole, and 2-methyl-5-nitroimidazole and for the determination of metronidazole and tinidazole in Metronidazole Polpharma and Tinidazolum Polpharma tablets. Analyses were performed on chromatographic plates precoated with silica gel 60F₂₅₄ using chloroform + methanol + diethylamine in a volume ratio of 9:1:1 as the optimal mobile phase. The method has been validated. The intraday and interday precision values for the three different concentrations ranged from 0.99% to 1.48% and 0.89% to 1.76%, and the precision values ranged from 1.13% to 2.48% and 0.95% to 2.49% for metronidazole and tinidazole, respectively. The limit of quantification (LOQ) was 0.036 and 0.066 µg/spot for metronidazole and tinidazole, respectively. The mean recovery was 103.1% and 100.6% for metronidazole and tinidazole, respectively. The content of metronidazole and tinidazole in tablets in relation to the content declared by the manufacturer was 101.3% and 99.8%, respectively. The obtained results were verified using the pharmacopeial method. The presented method is fast, sensitive, precise, selective, accurate, and robust. It allows for the analysis of several samples on one chromatography plate at the same time. Full article

Ornidazole is frequently used for the prevention and treatment of anaerobic infections after caesarean section. There is still a lack of data on the excretion of ornidazole in breast milk. Therefore, the aim of this study was to investigate the transfer of ornidazole into colostrum and to assess the risk of infant exposure to the drug via breast milk. Population pharmacokinetic analysis was conducted using datasets of plasma and milk concentrations obtained from 77 breastfeeding women to examine the excretion kinetics of ornidazole. Various factors that may affect the excretion of ornidazole were investigated. The final model was then used to simulate ornidazole concentration–time profiles in both plasma and milk. The drug exposure in body fluids and the potential risk for breastfeeding were assessed based on the safety threshold. Plasma ornidazole concentration data could be described well by a one-compartment model, and concentrations in breast milk were linked to this model using an estimated milk-to-plasma concentration ratio (MPRcon). Significant variables that influenced drug exposure and MPRcon were identified as total bilirubin levels (TBIL) and postnatal sampling time, respectively. Simulations showed that women with abnormal liver function (TBIL > 17 μmol/L) had higher ornidazole levels in plasma and milk than those with normal liver function (TBIL < 17 μmol/L), but the exposures through colostrum of lactating women from both groups were below the safety threshold. This work provides a simple and feasible strategy for the prediction of drug exposure in breast milk and the assessment of breastfeeding safety. Full article

Metronidazole, ornidazole, tinidazole, and secnidazole are 5-nitroimidazoles. The purpose of this work was to propose a new economical TLC–densitometric method to evaluate the chemical stability of metronidazole, secnidazole, ornidazole, and tinidazole under stress conditions. A forced degradation study was performed on silica gel and aqueous solutions at various pH values; the metronidazole, secnidazole, ornidazole, and tinidazole solutions were prepared in saline and in hydrogen peroxide, respectively. The samples of the 5-nitroimidazoles were heated. TLC analyses were performed on silica gel 60F₂₅₄ using chloroform–methanol (9:1, v/v) as the mobile phase. As the TLC–densitometric method can effectively separate the metronidazole, secnidazole, ornidazole, and tinidazole from their degradation products which formed as a result of the stress studies, it is considered to can be a good alternative and important tool in the routine quality control and stability testing of metronidazole, secnidazole, ornidazole, and tinidazole in pharmaceutical formulations. The results indicate that the proposed TLC–densitometric method is cost-effective, rapid, specific, accurate, and precise; the TLC–densitometric method also realizes the criterion of the linearity. A major advantage of the proposed method is its low cost and ability to analyze the 5-nitroimidazole which was investigated and all its degradation products simultaneously. Full article

Oropharyngeal avian trichomonosis is a potentially lethal parasitic disease that affects several avian orders. This review is focused on the disease treatments since prophylactic treatment is prohibited in most countries and resistant strains are circulating. A systematic review following the PRISMA procedure was conducted and included 60 articles. Successful and non-toxic treatments of avian oropharyngeal trichomonosis started with enheptin, a drug replaced by dimetridazole, metronidazole, ornidazole, carnidazole and ronidazole. Administration in drinking water was the most employed and recommended method, although hierarchy of the avian flocks and palatability of the medicated water can interfere with the treatments. Besides pigeons, treatments with nitroimidazoles were reported in budgerigars, canaries, finches, bald eagles, a cinereous vulture and several falcon species, but resistant strains were reported mainly in domestic pigeons and budgerigars. Novel treatments include new delivery systems proved with traditional drugs and some plant extracts and its main components. Ethanolic extracts from ginger, curry leaf tree and Dennettia tripetala, alkaloid extracts of Peganum harmala and essential oils of Pelargonium roseum and some Lamiaceae were highly active. Pure active compounds from the above extracts displayed good anti-trichomonal activity, although most studies lack a cytotoxicity or in vivo test. Full article

Nosema ceranae Fries, 1996, causes contagious fungal nosemosis disease in managed honey bees, Apis mellifera L. It is associated around the world with winter losses and colony collapse disorder. We used a laboratory in vivo screening assay to test curcumin, fenbendazole, nitrofurazone and ornidazole against N. ceranae in honey bees to identify novel compounds with anti-nosemosis activity compared to the commercially available medication Fumagilin-B^®. Over a 20-day period, Nosema-inoculated bees in Plexiglas cages were orally treated with subsequent dilutions of candidate compounds, or Fumagilin-B^® at the recommended dose, with three replicates per treatment. Outcomes indicated that fenbendazole suppressed Nosema spore proliferation, resulting in lower spore abundance in live bees (0.36 ± 1.18 million spores per bee) and dead bees (0.03 ± 0.25 million spores per bee), in comparison to Fumagilin-B^®-treated live bees (3.21 ± 2.19 million spores per bee) and dead bees (3.5 ± 0.6 million spores per bee). Our findings suggest that Fumagilin-B^® at the recommended dose suppressed Nosema. However, it was also likely responsible for killing Nosema-infected bees (24% mortality). Bees treated with fenbendazole experienced a greater survival probability (71%), followed by ornidazole (69%), compared to Nosema-infected non-treated control bees (20%). This research revealed that among screened compounds, fenbendazole, along with ornidazole, has potential effective antifungal activities against N. ceranae in a controlled laboratory environment. Full article

Concerns regarding increasing antibiotic resistance raise the question of the most appropriate oral antibiotic for empirical therapy in dentistry. The aim of this systematic review was to investigate the antibiotic choices and regimens used to manage acute dentoalveolar infections and their clinical outcomes. A systematic review was undertaken across three databases. Two authors independently screened and quality-assessed the included studies and extracted the antibiotic regimens used and the clinical outcomes. Searches identified 2994 studies, and after screening and quality assessment, 8 studies were included. In addition to incision and drainage, the antibiotics used to manage dentoalveolar infections included amoxicillin, amoxicillin/clavulanic acid, cefalexin, clindamycin, erythromycin, metronidazole, moxifloxacin, ornidazole and phenoxymethylpenicillin. Regimens varied in dose, frequency and duration. The vast majority of regimens showed clinical success. One study showed that patients who did not receive any antibiotics had the same clinical outcomes as patients who received broad-spectrum antibiotics. The ideal choice, regimen and spectrum of empirical oral antibiotics as adjunctive management of acute dentoalveolar infections are unclear. Given that all regimens showed clinical success, broad-spectrum antibiotics as first-line empirical therapy are unnecessary. Narrow-spectrum agents appear to be as effective in an otherwise healthy individual. This review highlights the effectiveness of dental treatment to address the source of infection as being the primary factor in the successful management of dentoalveolar abscesses. Furthermore, the role of antibiotics is questioned in primary space odontogenic infections, if drainage can be established. Full article

Novel coronavirus disease (COVID-19) was identified from China in December 2019 and spread rapidly through human-to-human transmission, affecting so many people worldwide. Until now, there has been no specific treatment against the disease and repurposing of the drug. Our investigation aimed to screen potential inhibitors against coronavirus for the repurposing of drugs. Our study analyzed sequence comparison among SARS-CoV, SARS-CoV-2, and MERS-CoV to determine the identity matrix using discovery studio. SARS-CoV-2 M^pro was targeted to generate an E-pharmacophore hypothesis to screen drugs from the DrugBank database having similar features. Promising drugs were used for docking-based virtual screening at several precisions. Best hits from virtual screening were subjected to MM/GBSA analysis to evaluate binding free energy, followed by the analysis of binding interactions. Furthermore, the molecular dynamics simulation approaches were carried out to assess the docked complex’s conformational stability. A total of 33 drug classes were found from virtual screening based on their docking scores. Among them, seven potential drugs with several anticancer, antibiotic, and immunometabolic categories were screened and showed promising MM/GBSA scores. During interaction analysis, these drugs exhibited different types of hydrogen and hydrophobic interactions with amino acid residue. Besides, 17 experimental drugs selected from virtual screening might be crucial for drug discovery against COVID-19. The RMSD, RMSF, SASA, Rg, and MM/PBSA descriptors from molecular dynamics simulation confirmed the complex’s firm nature. Seven promising drugs for repurposing against SARS-CoV-2 main protease (M^pro), namely sapanisertib, ornidazole, napabucasin, lenalidomide, daniquidone, indoximod, and salicylamide, could be vital for the treatment of COVID-19. However, extensive in vivo and in vitro studies are required to evaluate the mentioned drug’s activity. Full article

Biochar (BC)-supported nanoscale zero-valent iron (nZVI-BC) was investigated as a heterogeneous Fenton-like activator to degrade the antibiotic ornidazole (ONZ). The characterization of nZVI-BC indicated that BC could enhance the adsorption of ONZ and reduce the aggregation of nZVI. Thus, nZVI-BC had a higher removal efficiency (80.1%) than nZVI and BC. The effects of parameters such as the nZVI/BC mass ratio, pH, H₂O₂ concentration, nZVI-BC dose, and temperature were systematically investigated, and the removal of ONZ followed a pseudo-second-order kinetic model. Finally, possible pathways of ONZ in the oxidation process were proposed. The removal mechanism included the adsorption of ONZ onto the surface of nZVI-BC, the generation of •OH by the reaction of nZVI with H₂O₂, and the oxidation of ONZ. Recycling experiments indicated that the nZVI-BC/H₂O₂ system is a promising alternative for the treatment of wastewater containing ONZ. Full article

Developing multi-selective luminescence sensing technology to differentiate serial compounds is very important but challenging. White-light-emitting decoding sensing based on lanthanide metal-organic frameworks (Ln-MOFs) is a promising candidate for multi-selective luminescence sensing application. In this work, three isomorphic Ln-MOFs based on H₃dcpcpt (3-(3,5-dicarboxylphenyl)-5-(4-carboxylphenl)-1H-1,2,4-triazole) ligand, exhibiting red, blue, and green emission, respectively, have been synthesized by solvothermal reactions. The isostructural mixed Eu/Gd/Tb-dcpcpt is fabricated via the in-situ doping of different Ln³⁺ ions into the host framework, which can emit white light upon the excitation at 320 nm. It is noteworthy that this white-light-emitting complex could serve as a convenient luminescent platform for distinguishing eight frequently-used antibiotics: five through luminescence-color-changing processes (tetracycline hydrochloride, yellow; nitrofurazone, orange; nitrofurantoin, orange; sulfadiazine, blue; carbamazepine, blue) and three through luminescence quenching processes (metronidazole, dimetridazole, and ornidazole). Moreover, a novel method, 3D decoding map, has been proposed to realize multi-selective luminescence sensing applications. This triple-readout map features unique characteristics on luminescence color and mechanism. The mechanism has been systematically interpreted on the basis of the structural analysis, energy transfer and allocation process, and peak fitting analysis for photoluminescence spectra. This approach presents a promising strategy to explore luminescent platforms capable of effectively sensing serial compounds. Full article

The objective of the present study was to investigate the applicability of matrix type mucoadhesive oral multiple unit systems (MUS) for sustaining the release of ornidazole in the gastrointestinal tract (GIT).The MUS were prepared by ionotropic gelation method using chitosan and hydroxypropyl methyl cellulose K4M (HPMC K4M) according to 3² factorial designs and were evaluated in vitro and in vivo. The particle size length ranged from 0.78 to 1.30 mm and breadth from 0.76 to 1.30 mm, respectively. The entrapment efficiency was in range of 80 to 96%. The rapid wash-off test was observed faster at intestinal pH 6.8 as compared to acidic pH 1.2. The fluoroscopic study revealed the retention of MUS in GIT for more than 5 hours. The pharmacokinetic parameters C_max, T_max, mean residence time (MRT) and area under curve (AUC) of developed MUS were found to be improved significantly (p<0.05) when compared with marketed immediate release tablets each containing 500 mg of drug. This study demonstrates that the MUS could be a good alternative to immediate release tablets to deliver ornidazole and expected to be less irritant to gastric and intestinal mucosa. Full article

Methods for spectrophotometric determination of fenbendazole and ornidazde are described. The methods are based on the formation and extraction of the ion-pair complex formed between bromothymol blue and either fenbendazole (FBZ) or ornidazole (ORN). The extracted coloured complexes absorb at 416 and 446 nm, respectively. The effect of different factors, e.g. pH, organic solvent, reagent concentration, extraction time, shaking time and common interfering species have been investigated. Fenbendazole and ornidazole can be determined over the range 1.2 to 24.0 ppm and 5.5 to 77.0 ppm, respectively. The precision of the methods was tested for the determination of pure samples of FBZ and ORN and the mean RSD was found to be 3.0 and 2.3% for FBZ and ORN, respectively.The proposed methods were successfully applied for the determination of FBZ and ORN in commercially dosage fornis. A comparison between the suggested methods and the other reported methods was also studied. Full article