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Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(ε-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi’s diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 µg/cm2) than LNCs (12.7 ± 1.52 µg/cm2). The antifungal activity of the PNCs was high 19.07 mm compared to 11.4 mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections.

Background Cooperative defect is 1 of the earliest manifestations of disease patients with Alzheimer disease (AD) exhibit, but the underlying mechanism remains unclear. Methods We evaluated the cooperative function of APP/PS1 transgenic AD model mice at ages 2, 5, and 8 months by using a cooperative drinking task. We examined neuropathologic changes in the medial prefrontal cortex (mPFC). Another experiment was designed to observe whether miconazole, which has a repairing effect on myelin sheath, could promote the cooperative ability of APP/PS1 mice in the early AD-like stage. We also investigated the protective effects of miconazole on cultured mouse cortical oligodendrocytes exposed to human amyloid β peptide (Aβ1-42). Results We observed an age-dependent impairment of cooperative water drinking behavior in APP/PS1 mice. The AD mice with cooperative dysfunction showed decreases in myelin sheath thickness, oligodendrocyte nuclear heterochromatin percentage, and myelin basic protein expression levels in the mPFC. The cooperative ability was significantly improved in APP/PS1 mice treated with miconazole. Miconazole treatment increased oligodendrocyte maturation and myelin sheath thickness without reducing Aβ plaque deposition, reactive gliosis, and inflammatory factor levels in the mPFC. Miconazole also protected cultured oligodendrocytes from the toxicity of Aβ1-42. Conclusions These results demonstrate that mPFC hypomyelination is involved in the cooperative deficits of APP/PS1 mice. Improving myelination through miconazole therapy may offer a potential therapeutic approach for early intervention in AD.

The treatment of invasive aspergillosis caused by cryptic species remains a challenge due to the lack of randomised clinical trials and investigation of the efficacy and safety of different therapeutic strategies. We aimed to evaluate the in vitro activity of 23 conventional and new antifungal drugs against 54 clinical and environmental Aspergillus oryzae isolates by using the Clinical and Laboratory Standards Institute (CLSI) standard M38-A3. The lowest geometric mean MIC values were found for luliconazole and lanoconazole (0.001 μg/ml), followed by anidulafungin (0.104 μg/ml), posaconazole (0.15 μg/ml), itraconazole (0.37 μg/ml), efinaconazole (0.5 μg/ml), voriconazole (0.51 μg/ml), tavaborole (0.72 μg/ml), and amphotericin B (0.79 μg/ml). In contrast, ketoconazole, terbinafine, econazole, tioconazole, ravuconazole, miconazole, nystatin, clotrimazole, griseofulvin, sertaconazole, natamycin, tolnaftate, and fluconazole had no or low activity. Further studies are required to determine how well this in vitro activity translates into in vivo efficacy.

The crystal structures of miconazole {MIC, C18H14Cl4N2O, systematic name (RS)-1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole}, its ethanol monosolvate (C18H14Cl4N2O·C2H5OH) and its hemihydrate (C18H14Cl4N2O·0.5H2O) were compared. A detailed comparison of the molecular conformation of the miconazole molecules showed a structural similarity of the solvate forms, whereas the unsolvated form is related to the gas-phase structure. This suggests that the molecular conformation of miconazole is influenced by solvent molecules. The crystal architectures of the considered solvatomorphs are differentiated by the intermolecular interactions formed by ethanol and water molecules. The structural studies are enriched by Hirshfeld surface and energy framework analysis. The pairwise model energies of the dominant contacts were estimated to be in the range 20–70 kJ mol−1. It is interesting that the contribution of dispersive forces predominates over the electrostatic forces.

OBJECTIVE: This study investigated the antifungal and antibiofilm activity of Cymbopogon nardus essential oil (EO) and its major compound, citronellal, in association with miconazole and chlorhexidine on clinical strains of Candida albicans. The likely mechanism(s) of action of C. nardus EO and citronellal was further determined. MATERIALS AND METHODS: The EO was chemically characterized by gas chromatography coupled with mass spectrometry (GC-MS). The antifungal activity (MIC/MFC) and antibiofilm effects of C. nardus EO and citronellal were determined by the microdilution method, and their likely mechanism(s) of action was determined by the sorbitol and ergosterol assays. Then, the samples were tested for a potential association with standard drugs through the checkerboard technique. Miconazole and chlorhexidine were used as positive controls and the assays were performed in triplicate. RESULTS: The GC-MS analysis tentatively identified citronellal as the major compound in C. nardus EO. Both samples showed antifungal activity, with MIC of 256 µg/mL, as compared to 128 µg/mL and 8 µg/mL of miconazole and chlorhexidine, respectively. C. nardus EO and citronellal effectively inhibited biofilm formation (p < 0.05) and disrupted preformed biofilms (p < 0.0001). They most likely interact with the cell membrane, but not the cell wall, and did not present any synergistic activity when associated with standard drugs. CONCLUSION: C. nardus EO and citronellal showed strong in vitro antifungal and antibiofilm activity on C. albicans. CLINICAL RELEVANCE: Natural products have been historically bioprospected for novel solutions to control fungal biofilms. Our data provide relevant insights into the potential of C. nardus EO and citronellal for further clinical testing. However, additional bioavailability and toxicity studies must be carried out before these products can be used for the chemical control of oral biofilms.

Isoconazole with an asymmetrical carbon is a broad-spectrum antimicrobial imidazole, but there is still lack of relevant report about the potential enantioselectivity in biological samples. The object of this research was to develop and validate a sensitive and effective high performance liquid chromatography-electrospray ionization coupled with tandem mass spectrometry (HPLC-ESI-MS/MS) method for stereoselective separation and determination of isoconazole enantiomers in Sprague-Dawley (SD) rat plasma and tissues. The greater enantioseparation of isoconazole enantiomers was obtained on a Chiralpak IC column with a mobile phase consisted of acetonitrile-10 mM aqueous ammonium acetate (90:10, v/v) under the reversed-phase mode. Subsequently, the studied compounds and internal standard (IS) were detected on a multiple reaction monitoring (MRM) mode with positive electrospray ionization source. The experimental and theoretical Electronic Circular Dichroism (ECD) spectra were employed to confirm the absolute configuration of isoconazole enantiomers. Eventually, after full method validation, the newly developed method was successfully applied to the study of enantioselectivity in plasma and tissues in SD rats. Results illustrated that the enantioselective differences in plasma were observed for the evidence that the concentrations of S-(-)-isoconazole were always higher than R-(+)-isomer. In terms of tissue distribution, liver, kidney, lung, spleen, and small intestine were the mainly distributed tissues and then followed by heart and muscle. This is the first study to reveal the stereoselective behavior of isoconazole enantiomers in vivo, which also provides reliable and valuable reference for further elucidating the enantioselective metabolisms of isoconazole enantiomers.

Contact allergy has been reported as a side effect of topical antifungals (TAFs), although most evidence has come from small case series.To investigate the frequency and associated factors of contact allergy to TAFs.We performed a retrospective analysis of the data of the Contact Allergy Unit of a University Dermatology Department between January 2009 and April 2021. From a cohort of 3788 patients tested in our unit, aimed testing was performed in 482 patients using TAFs from Chemotechnique Diagnostics (Vellinge, Sweden), allergEAZE, and, in some cases, commercial preparations 'as is'.Contact allergy to antifungals was found in 27 patients (0.71% of consecutively tested patients and 5.6% of those who had aimed testing). Foot and leg eczema were the clinical presentation in 12 (44.4%) and 10 (37.0%) patients, respectively. Positive reactions were observed mostly with econazole nitrate 1% alcohol (51.9%), miconazole 1% alcohol (48.9%), tioconazole 28% solution (40.7%), and clotrimazole 5% pet. (18.5%). Fifteen patients (55.6%) had sensitization to more than one antifungal.Contact allergy to antifungals was uncommon and occurred mostly associated with foot dermatitis. Most patients were sensitized to more than one chemical, particularly to azoles, which may limit future choices of TAF treatment.

Purpose. To assess the improvement in oral bioavailability and efficacy in systemic candidiasis treatment of miconazole nitrate (MN) formulations in murine models of candidiasis. Methods. Selected formulations containing 5% of Softisan + Phospholipon 90H lipid matrix with 3% of MN ( A 1 ), 5% of stearic acid + Phospholipon 90H lipid matrix with 3% of MN ( B 1 ), and 5% Softisan + stearic acid + Phospholipon 90H with 3% of MN ( C 1 ) from the in vitro investigation were used for the study. Their acute toxicity was assessed using Lorke’s method (with slight modification) while bioavailability was determined using the bioassay method. The optimized batch ( A 1 ) was tested in murine systemic candidiasis induced in cyclophosphamide-immunosuppressed mice. The mice were treated with a single oral dose (100 mg/kg) of the formulations for five days. Serum fungal counts (cfu/mL) were determined on days 1, 3, and 5 of the treatment period. Haematological assessments were done. Results. The lipid formulations were safer than MN powder with LD50 values of 3162.8 and 1118.3 mg/kg. Bioavailability determination revealed a higher area under the curve (AUC) value for formulations A 1 (6.11 μg/hr/mL) and B 1 (4.91 μg/hr/mL) while formulation C 1 (1.80 μg/hr/mL) had a lower AUC than MN (4.46 μg/hr/mL). Fungi were completely cleared from the blood of animals treated with the optimized formulation by day 3 as opposed to the controls (MN and Tween® 20) which still had fungi on day 5. No significant increase ( p > 0.05 ) in haematological parameters was observed in mice treated with A 1 . Conclusion. Formulation A 1 successfully cleared Candida albicans from the blood within a shorter period than miconazole powder. This research has shown the potential of orally administered MN-loaded SRMS-based microparticles in combating systemic candidaemia.

Candida albicans is the fungus responsible for oral candidiasis, a prevalent disease. The development of antifungal-based delivery systems has always been a major challenge for researchers. This study was designed to develop a nanostructured lipid carrier (NLC) of sesame oil (SO) loaded with miconazole (MZ) that could overcome the solubility problems of MZ and enhance its antifungal activity against oral candidiasis. In the formulation of this study, SO was used as a component of a liquid lipid that showed an improved antifungal effect of MZ. An optimized MZ-loaded NLC of SO (MZ-SO NLC) was used, based on a central composite design-based experimental design; the particle size, dissolution efficiency, and inhibition zone against oral candidiasis were chosen as dependent variables. A software analysis provided an optimized MZ-SO NLC with a particle size of 92 nm, dissolution efficiency of 88%, and inhibition zone of 29 mm. Concurrently, the ex vivo permeation rate of the sheep buccal mucosa was shown to be significantly (p

This study aimed to evaluate the antifungal activity of grapefruit seed extract (GSE) against Candida species and to confirm the biological safety. Two-fold serial dilutions of GSE or miconazole were prepared. Cell suspensions of Candida albicans, Candida glabrata, Candida tropicalis, or Candida parapsilosis were added to each diluted solution, and the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined. The MFC/MIC ratio was calculated to determine whether the substance had a fungistatic or fungicidal activity. Each Candida species treated with GSE were examined using a scanning electron microscope (SEM) and fluorescence microscopy. The effect of GSE on EpiOral™, a three-dimensional tissue model, was assessed by tissue viability assay and histological analysis. GSE was applied to the mandibular gingiva of Japanese white rabbits, and the gingival tissues were histopathologically assessed. GSE demonstrated a fungicidal effect against all tested Candida species, whereas miconazole demonstrated a fungicidal effect against only C. albicans. SEM images showed various cell damage patterns in GSE-treated Candida cells. Fluorescence microscopy revealed that almost all Candida cells were killed by GSE-treated. EpiOral™ treated with GSE showed no effect on the tissue viability and there was no remarkable difference between GSE and control groups in the histological analysis. The histopathological observation in the oral mucosa treated with GSE showed no significant histopathological changes. Taken together, GSE has a fungicidal activity against C. albicans, C. glabrata, C. tropicalis, and C. parapsilosis, and no adverse effects were observed in vitro and in vivo.

Candida albicans and Candida tropicalis are the leading causes of human fungal infections worldwide. There is an increase in resistance of Candida pathogens to existing antifungal drugs leading to a need to find new sources of antifungal agents. Tormentic acid has been isolated from different plants including Callistemon citrinus and has been found to possess antimicrobial properties, including antifungal activity. The study aimed to determine the effects of tormentic and extracts from C. citrinus on C. albicans and C. tropicalis and a possible mode of action. The extracts and tormentic acid were screened for antifungal activity using the broth microdilution method. The growth of both species was inhibited by the extracts, and C. albicans was more susceptible to the extract compared to C. tropicalis. The growth of C. albicans was inhibited by 80% at 100 μg/ml of both the DCM: methanol extract and the ethanol: water extract. Tormentic acid reduced the growth of C. albicans by 72% at 100 μg/ml. The effects of the extracts and tormentic acid on ergosterol content in C. albicans were determined using a UV/Vis scanning spectrophotometer. At concentrations of tormentic acid of 25 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml, the content of ergosterol was decreased by 22%, 36%, 48%, and 78%, respectively. Similarly, the DCM: methanol extract at 100 μg/ml and 200 μg/ml decreased the content by 78% and 88%, respectively. A dose-dependent decrease in ergosterol content was observed in cells exposed to miconazole with a 25 μg/ml concentration causing a 100% decrease in ergosterol content. Therefore, tormentic acid inhibits the synthesis of ergosterol in C. albicans. Modifications of the structure of tormentic acid to increase its antifungal potency may be explored in further studies.

The aim of the present work was to formulate and evaluate Miconazole nitrate (MN) polymeric nanoparticles (NPs) for systemic delivery of the active ingredient after topical administration. The Solvent evaporation approach was used to make nanoparticles for topical delivery of MN. Particle size, entrapment efficiency and SEM were all measured in MN-SLN. A consistent size distribution (PI 0.300) was used to generate aqueous NPs dispersions with a mean particle size less than 250 nm. After 3 months of storage, the produced semi-solid systems had a mean particle size of less than 250 nm and a PI of less than 0.500. The F5 formulation was been chosen as the model formulation from among the nine nanoparticle formulations developed (F1 to F9). The reason for this was that, according to the ICH stability guidelines, formulation F5 was judged to be optimal and stable. The F5 formulations of miconazole nanoparticles shows the highest entrapment efficiency (93.28%) and drug loading (86.64%). In conclusion, there are two major advantages of using miconazole nanoparticle drug delivery systems. i.e., they are topical preparations that assemble in the hair follicles and wrinkles to produce a systemic and local action. It is possible that nanoparticles will be the most effective treatment for fungal skin infections.

Serious oral mucositis develops during radiation therapy (RT) for head and neck cancer, but there is no effective preventive method. We have used a steroid ointment to prevent oral mucositis during RT, but the use of steroid ointment is discontinued when oral candidiasis develops. Therefore, prevention of oral candidiasis is important. The purpose of this study was to examine whether administration of a miconazole oral patch reduced the amount of Candida albicans in saliva and prevented the development of oral candidiasis during RT. Participants were patients with head and neck cancer receiving RT ≥ 60 Gy. Patients in the intervention group received miconazole oral patches for 14 days after the appearance of grade 2 oral mucositis. The control group received oral care only. Total bacteria and C. albicans counts in the saliva were analyzed by real-time polymerase chain reaction. The incidence of oral candidiasis was compared between the groups. Total bacterial counts did not change throughout RT in either the intervention or the control group. However, C. albicans count significantly increased at 30 Gy and 60 Gy in the control group but was suppressed in the intervention group. The saliva pH did not show a significant change throughout RT in either group. The incidence of oral candidiasis in the intervention group tended to be lower than that in the control group. This study suggested that prophylactic use of a miconazole oral patch was effective in suppressing the growth of C. albicans count in saliva during RT for head and neck cancer.

Aseries of 1-(2-aryloxy-2-phenylethyl)-1,2,3-triazole derivatives (Miconazole analogs) was obtained via copper catalyzed azide-alkyne cycloaddition as the key step. The synthesized compounds were evaluated for antimicrobial activity against Candida genus strains as well as filamentous fungi (Mucor hiemalis, Aspergillus fumigatus and Rhizopus oryzae). A 1-(2-aryloxy-2-phenylethyl)-1,2,3-triazole derivative exhibited remarkable selectivity comparable to that of Itraconazole against Rhizopus oryzae.

Topical preparations have a problem of being wiped off after a short time, which results in low activity of the active moiety. In this research, topical organogels (OGs) were prepared with different oils for the controlled action of miconazole nitrate. Various oils were checked for their gel-forming ability. Controlled release OGs were prepared with a 15% concentration of glyceryl monostearate. Differential scanning calorimetry was performed to study the thermal behavior of gels. X-ray diffraction revealed that the drug was changed into an amorphous form from the crystalline form. The absence of any interaction between the active ingredient and excipients was concluded by Fourier Transform Infrared spectroscopy. Permeability studies were carried out with cellulose acetate membrane by using Franz diffusion cell containing phosphate buffer saline pH 7.4. The release of drug followed the Weibull model. A frequency sweep test was performed to study the rheological behavior of optimized formulations. Rheology revealed the true nature of formulations whether they are gels or just viscous fluids. Images of scanning electron microscopy showed a network formed by the gelator molecules. The antifungal activity was checked against C. albicans and A. niger and it was best by the formulation made by TT. It was concluded that all the OGs gave controlled topical antifungal action.

Oropharyngeal candidiasis (OPC) is an opportunistic infection treated with anti-fungal agents. Herein, we evaluate the efficacy and safety of miconazole buccal tablets (MBT) and itraconazole capsules in the localized treatment of patients with OPC. In this multi-centered, double-blinded, phase III trial (CTR20130414), both males and non-pregnant females (≥18 years) with OPC were randomized (1:1) to MBT plus placebo (experimental group) or itraconazole capsules plus placebo (control group). The primary endpoint was clinical cure at the end-of-treatment period [visit 4 (V4)] while secondary endpoints were clinical remission rates, partial remission rates, mycological cure, clinical relapse, and adverse events (AEs). All endpoints were statistically analyzed in both the full analysis set (FAS) and per-protocol (PP) set. A total of 431 (experimental: 216; control: 215) subjects were included. At V4, in the FAS set, the clinical cure was achieved in 68% and 59% patients in experimental and control groups, respectively with a treatment difference of 9% [95% confidence interval (CI): -1,19; P.001] demonstrating non-inferiority of MBT over itraconazole. At V4, mycological cure rates were 68.2% and 42.0% in the experimental group and control groups (P.001), respectively in FAS. The relapse rates were 5.4% and 6.6%, respectively, in the experimental and control groups. A total of 210 patients experienced AEs during treatment with 47.7% in the experimental group and 49.8% in the control group with no deaths. This study demonstrated that once-daily treatment with MBT was non-inferior to itraconazole with higher mycological cure rates and was tolerable with mild AE in patients with OPC.Miconazole is an antifungal drug against certain types of fungus or yeast infections. In this study, we showed that treatment with once-daily miconazole buccal tablets was as effective as systemic itraconazole capsules in Chinese patients infected by oropharyngeal candidiasis with minimum side effects.

Objective To present and evaluate the treatment of keratosis obturans (KO) using miconazole/triamcinolone 0.1% creme gauzes. Study design A retrospective clinical capsule report. Patients Twelve patients diagnosed with KO between January 2000 and July 2020 visiting our tertiary hospital setting, were retrospectively reviewed. Interventions Either miconazole/triamcinolone 0.1% creme gauzes or periodic microscopic removal of the keratin plug. Main outcome measures No evidence of disease during microscopic inspection of the ear canal. Results Successful treatment with miconazole/triamcinolone 0.1% gauzes was seen in 4/7 patients (57%) and successful treatment of periodic cleaning of the ear canal was seen in 1/5 patients (20%). Conclusions Topical treatment of KO with miconazole/triamcinolone 0.1% creme gauzes in the ear canal could be considered as a treatment option for patients diagnosed with KO.

This article reports the results obtained from the investigation of the influence of miconazole administration on the physiological fluctuation of the markers of the steroid profile included in the “steroidal module” of the Athlete Biological Passport. Urines collected from male Caucasian subjects before, during, and after either systemic (i.e., oral and buccal) or topical (i.e., dermal) treatment with miconazole were analyzed according to validated procedures based on gas chromatography coupled to tandem mass spectrometry (GC–MS/MS) (to determine the markers of the steroid profile) or liquid chromatography coupled to MS/MS (LC–MS/MS) (to determine miconazole urinary levels). The results indicate that only after systemic administration, the markers of the steroid profile were significantly altered. After oral and buccal administration, we have registered (i) a significant increase of the 5α‐androstane‐3α,17β‐diol/5β‐androstane‐3α,17β‐diol ratio and (ii) a significant decrease of the concentration of androsterone, etiocholanolone, 5β‐androstane‐3α,17β‐diol, and 5α‐androstane‐3α,17β‐diol and of the androsterone/etiocholanolone, androsterone/testosterone, and 5α‐androstane‐3α,17β‐diol/epitestosterone ratios. Limited effects were instead measured after dermal intake. Indeed, the levels of miconazole after systemic administration were in the range of 0.1–12.5 μg/ml, whereas after dermal administration were below the limit of quantification (50 ng/ml). Significant alteration started to be registered at concentrations of miconazole higher than 0.5 μg/ml. These findings were primarily explained by the ability of miconazole in altering the kinetic/efficacy of deglucuronidation of the endogenous steroids by the enzyme β‐glucuronidase during the sample preparation process. The increase of both incubation time and amount of β‐glucuronidase was demonstrated to be effective countermeasures in the presence of miconazole to reduce the risk of uncorrected interpretation of the results., The results obtained from the investigation of the influence of miconazole administration on the parameters included in the “steroidal module” of the Athlete Biological Passport were presented. After oral and buccal administration of miconazole, the levels of the markers of the steroid profile were significantly altered, whereas no effects were registered after topical administration. These findings were primarily explained by the effect of miconazole on the kinetics/efficacy of the enzymatic hydrolysis during the sample preparation process.

The study aimed to investigate the in vitro antifungal activity of miconazole entrapped in microemulsion based gel with clove oil as permeation enhancer and chitosan as antifungal agent. SEM confirmed spherical droplets of microemulsion in the 2 micron size range. The viscosity of emugel was 2251 cP, excellent spreadability 31.27 ±0.219 g.cm/cc as compared to marketed formulation. pH was 5.528 ± 0.032, homogeneity was excellent and drug content was 98 % in optimized batch. No drug-excipients interaction was reported in FTIR spectroscopy. In vitro drug release showed 94.8 % in 6 h. Ex vivo skin permeation showed higher steady state flux than conventional cream. Antifungal activity on Candida albicans showed a zone of inhibition more than that of marketed preparation. Thus, it can be concluded that the formulation may hold some promise for the treatment of severe fungal infections.

Navicula arenaria Donkin 1861 is a marine microalga belongs to class of bacillariophycea. Recently, microalgae and their products are used as biological control of diseases caused by phytopathogenic fungi. This is considered environmentally ecofriendly method to overcome the plant damage caused by soil borne pathogenic fungi and thereby economic loss. Therefore, this study aimed to investigate in vitro the antifungal activity of N. arenaria isolate PS 31 extracellular and intracellular metabolites against two taxa of soil borne phytopathogenic fungi; Macrophomina phaseolina and Fusarium oxysporum. N. arenaria PS 31 hexane extract was the most effective extract on growth inhibition of both phytopathogenic fungi. There is no significant difference between miconazole and N. arenaria hexane extract of 5.6 mg/ml on growth inhibition of F. oxysporum. The inhibitory effect of hexane extract at 5.6, 4.2 and 2.8 mg/ml and ethyl acetate extract at 35% (v/v) was higher than controls. Ethyl acetate extract was effective on growth inhibition of M. phaseolina (29.67%). GC-MS analysis of N. arenaria hexane fraction revealed the presence of potent antifungal compounds such as Phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-, di-n-octyl phthalate, cholestane-3,5-diol, 5-acetate,(3.beta.,5.alpha.), Cholestan-3-ol,(3.beta.,5.beta.)- and beta.-Sitosterol. These results suggest that N. arenaria hexane extract can be used in biological control of plant diseases caused by M. phaseolina and F. oxysporum.

Topical preparations of allylamines and imidazoles are the commonly used medications for the treatment of tinea corporis, having extended efficacy and good safety profile. In our study, we have compared topical terbinafine, an allylamine and topical miconazole, which is an imidazole to assess their efficacy and safety in tinea corporis infection. Hundred patients with tinea corporis infection were equally randomized to receive either terbinafine (1%) or miconazole (2%) for 4 weeks. The reduction in clinical symptoms (pruritus, erythema, vesicle, and desquamation), attaining mycological cure, reduction in composite score, as well as physician global assessment were evaluated from baseline to the end of intervention, and at follow up visit, and compared between the groups. Incidence of adverse drug reactions was also noted for safety analysis. Baseline demographic characteristics of terbinafine and miconazole groups were similar. The study demonstrated statistical significance reduction in clinical symptom scores, attaining Mycological cure, composite score and Physician Global Assessment from baseline to 4th week and follow up week between both groups with a p value

OBJECTIVE: To summarize and evaluate the effectiveness and safety of Redcore lotion on treating vulvovaginal candidiasis (VVC) using a systematic review and Meta-analysis of randomized controlled trials. METHODS: A systematic literature search was performed in five English and three Chinese electronic databases up to October 2019. Randomized controlled trials in the treatment for VVC were included; only studies which compared the effectiveness and safety of Redcore lotion plus miconazole with miconazole alone were included. Relative risk (RR) and 95% confidence intervals (CI) were used in the Meta-analysis. RESULTS: Seven studies involving 768 patients suffering from VVC were identified; 468 of the patients were pregnant women (60.9%). Combination group (Redcore lotion plus miconazole) was more effective in reduCIng symptomatic episodes of VVC than miconazole alone, with respect to cure rate (RR, 1.31; 95% CI, 1.09-1.57; P = 0.01), fungal culture negative rate (RR, 1.21; 95% CI, 1.04-1.41; P = 0.01), and effective rate (RR, 1.18; 95% CI, 1.05-1.35; P = 0.01). Subgroup analyses for pregnant women also showed that the combination group had superior outcomes with respect to VVC cure rate (RR, 1.48; 95% CI, 1.16-1.88, P < 0.01), fungal culture negative rate (RR, 1.26; 95% CI; 1.09-1.47; P < 0.01), and effective rate (RR, 1.25; 95% CI, 1.10-1.42; P < 0.01). Additionally, the observed risk of adverse events was lower in the combination medication group (RR, 0.30; 95% CI, 0.14-0.65; P < 0.01). CONCLUSION: Though overall quality of individual studies was low, Redcore lotion plus miconazole can significantly improve clinical effectiveness and safety compared with miconazole alone.

Tineacorporis is a dermatophytic infection of the body, which involves the keratin layer of the skin. These lesions are present as an annular plaque with an advancing border along with central clearing. Miconazole, a topical antifungal drug and has good efficacy, in anti dermatophyte. Sertaconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase.It is claimed to be superior to other old topical imidazoles in tineacorporis. .The present study was aimed to compare the safety, efficacy and cost-effectiveness of topical antifungals, where we have compared Miconazole and Sertaconazole 2% creams in the treatment of fungal infection caused by tineacorporis, by assessing the ADR’s and therapeutic outcomes, using comparative, unicentered, randomized, non-blinded trial with 2 parallel treatment arms of one-month duration. In this study 106 patients were randomly assigned into 2 groups of Miconazole 2% cream and Sertaconazole 2% with 54 and 52 patients in each group respectively. Measurement is carried out at baseline, 1st, 2nd and 3rd follow-up for desired effects like itching, erythema, pain and lesions, physician’s global assessment (PGA), safety and cost-effectiveness. The results showed that sertaconazole 2% cream is efficacious and superior to Miconazole 2% cream in the improvement of clinical parameters and PGA. At the end of the follow-up phase, both groups of drugs are effective and well-tolerated in patients with no recurrence of tineacorporis. Effectiveness of SSertaconazole is early and superior with minor side effects. However, Miconazole is cost effective and safe.

Elevated numbers of candida in the oral cavity often lead to oral candidiasis development in patients undergoing radiotherapy for oral or oropharyngeal cancer. This study aimed to verify the efect of iconazole mucoadhesive tablets on suppression of oral candida infection during radiotherapy. For this preliminary interventional study, miconazole mucoadhesive tablets were attached to the oral mucosa for 14 days from when grade 2 oral mucositis appeared in patients with oral or oropharyngeal cancer receiving radiotherapy, and the incidence of oral candidiasis was investigated. Various clinical factors were examined; univariate and multivariate Cox regression analyses were performed to investigate and compare the efcacy of this drug in preventing oral candidiasis with results of our previous study as historical control. Miconazole mucoadhesive tablets were administered to 18 patients, and oral candidiasis was observed in one patient (5.6%) after treatment completion. Among 144 historical control patients, 43 (29.9%) developed oral candidiasis. Multivariate Cox regression showed that miconazole mucoadhesive tablets signifcantly reduced oral candidiasis development during radiotherapy (p= 0.049, Hazard ratio 0.136, 95% confdence interval 0.019–0.994). This preliminary study suggests the efcacy of miconazole mucoadhesive tablets in preventing oral candidiasis in oral or oropharyngeal cancer patients treated with radiotherapy., Scientific Reports, 12 (1), art. no. 10188; 2022

Human cytochrome P450 8B1 (CYP8B1) is involved in conversion of cholesterol to bile acids. It hydroxylates the steroid ring at C12 to ultimately produce the bile acid cholic acid. Studies implicated this enzyme as a good drug target for nonalcoholic fatty liver disease and type 2 diabetes, but there are no selective inhibitors known for this enzyme and no structures to guide inhibitor development. Herein, the human CYP8B1 protein was generated and used to identify and characterize interactions with a series of azole inhibitors, which tend to be poorly selective P450 inhibitors. Structurally related miconazole, econazole, and tioconazole bound with submicromolar dissociation constants and were effective inhibitors of the native reaction. CYP8B was cocrystallized with S-tioconazole to yield the first X-ray structure. This inhibitor bound in the active site with its azole nitrogen coordinating the heme iron, consistent with inhibitor binding and inhibition assay data. Additionally, the CYP8B1 active site was compared with similar P450 enzymes to identify features that may facilitate the design of more selective inhibitors. Selective inhibitors should promote a better understanding of the role of CYP8B1 inhibition in normal physiology and disease states and provide a possible treatment for nonalcoholic fatty liver disease and type 2 diabetes.

Introduction Dermatophytosis is a common skin disease in cats and dogs caused by Microsporum and Trichophyton fungi. Species identification and knowledge of their antifungal susceptibility are therapeutically and epidemiologically important. This study assessed the prevalence of feline and canine dermatophytosis in Iran, identified the aetiological agents molecularly and tested their antifungal susceptibility. Material and Methods A total of 308 companion animals (134 dogs and 174 cats) with skin lesions were examined from March 2015 to March 2018. Hair and skin samples were examined by microscopy with 20% KOH and cultured on Sabouraud dextrose agar with cycloheximide and chloramphenicol. Fungal isolates were confirmed by sequencing of the internal transcribed spacer (ITS) r-DNA region. The antifungal susceptibility of dermatophytes was tested by broth microdilution assay using standard drugs. Results Dermatophytes were found in 130 (42.2%) samples, 62 of them feline and 68 canine. Based on sequencing of all strains, M. canis (78.5%, PM. gypseum (10.7%), and T. mentagrophytes (10.7%) were the dermatophytes isolated. The non-dermatophyte species Nannizziopsis vriesii was also isolated from two feline dermatomycosis cases. Dogs and cats younger than one year (61.5%) showed a statistically significantly higher prevalence of infection (P Conclusion This is the first molecular study to identify the causes of pet dermatophytosis in north-western Iran. ITS-PCR was shown to be a useful and reliable method for the identification of closely related species of dermatophytes in clinical and epidemiological settings. The lowest MIC of caspofungin indicated that this drug was the most potent in vitro.

Background Trichophyton mentagrophyte (TM), a zoonotic pathogen, has been endangering public health due to emerging drug resistance. Although increased attention is paid to this issue, there is very limited research available on drug resistance in TM. In this study, we studied the gene and proteomic changes, morphological changes, cellular fat localization, fat content changes, and biofilm of TM treated with different substances. Results The TM growth curve showed a positive correlation with the concentration of Fenarimol (FE), genistein (GE), clotrimazole (KM), and Miconazole nitrate salt (MK). The morphology of TM cells changed in different degrees after treatment with different substances as observed by TEM and SEM. The results showed that under KM and berberine hydrochloride (BB) treatment, a total of 3305 differentially expressed genes were detected, with the highest number in the KM-treated group (578 up-regulated and 615 down-regulated). A total of 847 proteins and 1850 peptides were identified in TM proteomics. Nile red staining showed that the fat content of TM was significantly higher in the BB-, ethidium bromide- (EB), FE-, KM-, Adriamycin hydrochloride- (YA), and MK-treated group compared to the control group. Results of the biofilm thickness showed that it gradually increased under treatment with specific concentrations of KM or BB, which may be related to the up-regulation of ERG25 and CYP related gene proteins. Conclusions It is suggested that in order to effectively deal with dermatomycosis caused by TM, it is necessary to inhibit the expression of ERG25 and CYP related genes and fat metabolism, which can result in the inhibition of the production of biofilm by the fungus and solve the problem of fungal drug resistance in clinical settings.

The main aims of this investigation were the isolation of dimeric naphthoquinones, a new class of dinaphthodiospyrols (1-7), from chloroform fractions and screening them for antibacterial, antifungal, and antioxidant potential. The susceptibility of the isolated compounds, namely, dinaphthodiospyrol A (1), dinaphthodiospyrol B (2), dinaphthodiospyrol C (3), dinaphthodiospyrol D (4), dinaphthodiospyrol E (5), dinaphthodiospyrol F (6), and dinaphthodiospyrol G (7) was assessed for antibacterial potential using well diffusion methods. The isolated compounds showed excellent antibacterial activity against selected bacterial strains, including Gram-positive Bacillus subtilis, Streptococcus epidermis, and Bacillus subtilis, and Gram-negative bacteria Klebsiella pneumonia with the zones of inhibition 6 to 26 nm. The standard drug Imipenem showed a maximum inhibitory zone 30 to 35 nm. Similarly, the isolated compounds were screened for antifungal properties, which showed an excellent reduction in the growth of selected fungal strain including Candida albicans, Aspergillus flavus, Fusarium solani, Trichyton logifusus, Microsporum canis , and Candida glabrata. Among all the screened compounds, 7 exhibited good activity (30-49 mm), followed by compounds 5 and 6, (35-46 mm), while compounds 1-4 showed a moderate effect (8-28 mm) against the selected fungal strain against miconazole which showed potent effects (101-110.98 mm). The isolated compounds were also screened for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) activity. In vitro-based free radical was employed using ascorbic acid as a standard antioxidant. The tested compounds (1-7) exhibited significant antioxidant activity in a concentration-dependent manner. The dinaphthodiospyrol 7 exhibited 97.32% scavenging activity, followed by dinaphthodiospyrol 6, 92.01%, and compounds 5 and 4 with 89.90 and 88.43% scavenging activity at 100 μg/mL, respectively; ascorbic acid showed 96.45% scavenging effect. Furthermore, docking analysis was performed to know the exact binding mode of the tetra-substituted derivatives of dinaphthodiospyrols to the selected target proteins. From the docking analysis, it was found that the docking results are well correlated with the experimental observations. In conclusion, the dinaphthodiospyrols exhibited excellent antibacterial, antifungal, and free radical scavenging potential.

Statement of problem The comparative efficacy of antifungal drugs on oral candidiasis remains unclear. Purpose The purpose of this Bayesian network meta-analysis was to investigate the efficacy of antifungal drugs on oral candidiasis. Material and methods Databases, including PubMed, The Cochrane Library, and Web of Science, were accessed from the dates of their establishment to October, 2018, to collect randomized controlled trials (RCTs) of different antifungal drugs for oral candidiasis. A network meta-analysis was then conducted by using R and Stata 12.0 software programs. Results A total of 31 RCTs involving 4042 participants were included. The meta-analysis showed that, in the treatment of oral candidiasis in reducing the mycological cure rate, itraconazole capsules, itraconazole oral solution, miconazole buccal tablets, miconazole oral gel, clotrimazole, fluconazole, ketoconazole, nystatin, and amphotericin B were better than a placebo. Miconazole oral gel, fluconazole, and ketoconazole were better than nystatin. The network meta-analysis also showed that the effects of antifungal drugs in reducing the mycological cure rate in oral candidiasis were better than those of a placebo: itraconazole capsule (OR=1.20, 95% CrI: 1.07-1.34), itraconazole oral solution (OR=1.50, 95% CrI: 1.14-1.86), miconazole buccal tablet (OR=2.80, 95% CrI: 1.20-4.50), miconazole oral gel (OR=2.90, 95% CrI: 1.70-4.30), clotrimazole (OR=3.80, 95% CrI: 1.65-5.95), fluconazole (OR=2.40, 95% CrI: 1.10-3.80), ketoconazole (OR=3.40, 95% CrI: 1.76-7.04), nystatin (OR=2.50, 95% CrI: 1.43-3.57), and amphotericin B (OR=2.60, 95% CrI: 1.91-3.29). The SUCRA values for each antifungal drug were as follows: placebo (6.80%), itraconazole capsule (51.2%), itraconazole oral solution (75.2%), miconazole buccal tablet (34.4%), miconazole oral gel (76.9%), clotrimazole (64.8%), fluconazole (79.3%), ketoconazole (50.7%), nystatin (15.7%), and amphotericin B (44.4%). Conclusions Antifungal drugs have efficacy in the treatment of oral candidiasis. The effect of fluconazole in reducing the risk of the mycological cure rate in oral candidiasis was better than that of other drugs.

Antibiotic effectively controls the bacterial and fungal infections. Pathogens developing multi-drug resistance are a global health concern, which necessitate developing new molecules to overcome the resistance dilemma. This study explores the intrinsic ability of marine oysters synthesizing bioactive compounds. The tissue extracts prepared in n-hexane from two oysters, Magallana bilineata and Magallana cuttackensis compared for broad spectral antimicrobial activates against the fungal, Gram positive and negative pathogens. Regardless, both the species tolerated the same pollution indices; the M. bilineata exhibits stronger antimicrobial activities as compared to M. cuttackensis. M. bilineata potentially inhibited the bacterial growth with minimal inhibitory concentration (0.75–20 μg/ml) and fungal pathogens (0.75–5 μg/ml) as compared to ciprofloxacin and miconazole. Inhibitory potential complimented with reduce bactericidal and fungicidal concentrations required to observed susceptible zone of inhibition (ZOI). The inhibition augmented with increased antimicrobial index (AMI) and total activity index (TAI) against the human pathogen than those of M. cuttackensis. It is widely acknowledged that there is a need to develop novel antimicrobial agents to minimize the threat of emerging multiple antimicrobial resistant pathogens. Therefore, the oysters surviving in the pollution stress modulate the physiological and immune response may exploit to develop potential antibiotics.

In the current research, attempt is made to fabricate a nanoemulsion (NE) containing an antifungal agent. The prepared formulation has been expected to enhance skin penetration. It is also studied for in vitro drug release and toxicity assessment. Spontaneous titration method was used for preparation of NE. Prepared NE were characterized for their charge, size, morphology, rheological behaviour, drug release profile, skin permeability. The drug permeation and skin irritation were investigated. The in vitro antifungal activity was inspected using the well agar diffusion method. Miconazole NE showed good penetration in the skin as compared to marketed products. SEM showed semispherical shapes of the droplets. Zeta potential and zeta sizer showed that size was in nano ranges having positive charge.

Introduction SO-1105 is an oral mucosal adhesive tablet containing 50 mg of miconazole. It had been shown overseas that a once-daily application of the drug continues antifungal effect in the treatment of oropharyngeal candidiasis. We report the results of the phase 3 clinical study of this drug with miconazole gel as a control in Japan. Methods The study included patients aged 20 years or older with oropharyngeal candidiasis who had oral lesions characterized by oropharyngeal candidiasis and whose fungi was confirmed by direct microscopic examination. The primary efficacy endpoint was the clinical cure rate on Day15 after 14 days of administration. The population analyzed for efficacy was per protocol set (PPS). Results 120 subjects were included in PPS. In detail, 59 subjects were in the SO-1105 group (SO-1105 group) and 61 subjects were in the miconazole gel group (Gel group). For efficacy, the clinical cure rate on Day15 was 47.5% in SO-1105 group and 47.5% in Gel group, showing the similar efficacy between both groups. For safety, adverse drug reactions were observed in 29.0% of SO-1105 group and 24.6% of Gel group, showing the similar safety between both groups. Conclusion The efficacy of SO-1105 was shown to be similar to that of miconazole gel. Meanwhile, SO-1105 is an adhesive tablet and is administered once-daily. For this, SO-1105 is expected to better compliance and useful drug for the elderly. Therefore, SO-1105 is considered to be widely used in clinical practice as one of the therapeutic drugs for oropharyngeal candidiasis.

The search for potent therapeutic agents has prompted the design and synthesis of a library of twenty-six aryloxy-tethered and amide-linked symmetrical 1,2,3-triazoles (8a–z) using a copper(I)-catalyzed click chemistry approach. All the synthesized compounds have been screened for their in vitro antifungal activity against four different fungal strains as well as the enzymatic study for the inhibition of 14 α-demethylase enzyme. The bioactivity results show that most of the synthesized compounds were found to be better antifungal agents as compared to Miconazole. Among them, compound 8a showed the most promising antifungal activity against all the tested fungal strains. Furthermore, the enzymatic study reveals that compounds 8i and 8o are the most promising inhibitors of the 14 α-demethylase enzyme. In support of these results, the molecular docking study of the synthesized molecules against the sterol 14 α-demethylase (CYP51) could provide the structural basis for the antifungal activity. These compounds have also been analyzed for the ADME properties.

In vitro activity of miconazole, salicylic acid and benzoic acid against T.richophyton mentagrophytes was done on Sabouraud’s dextrose agar. The inhibition zones were measured in cm. 2.8 cm, 1.5 cm and no inhibition zone were reported for miconazole, salicylic acid and benzoic acid respectively. Synergistic effect of salicylic acid and benzoic acid against T. mentagrophytes was done using two different bases of cream lanette 20% and aqueous cream 30/70. Four different formula each one contain 2% miconazole with different concentrations of salicylic acid and benzoic acid were used. Biggest inhibition zone (5 cm) was observed of lanette cream which contains 2% miconazole, 3% salicylic acid and 6% benzoic acid.

Dermatophytosis is one of the most frequent fungal skin diseases of pet animals, with high cost of treatment, and difficult control measures. Also, the disease has an important public health consequence. In our study, during a period of 2 year, 183 cats with cutaneous lesions were examined using direct microscopic examination and by fungal culture on Sabouraud Dextrose Agar (SDA). Out of 183 suspected samples, 94 cultured positive (51.4%). Where 73 samples showed colonies of M. canis (77.7%), while 13 showed T. mentagrophytes colonies (13.8%) and only 4 samples (4.3%) yielded mixed infection (M. canis and T. mentagrophytes). One sample (1.1%) was positive for M. gypseum, one sample (1.1%) for T. verrucosum, one sample (1.1%) for T. phaseoforme and one sample (1.1%) for T. violaceum. Randomly, 25 dermatophytes-infected cats were allocated into 5 groups (5 cats each) where they are treated using topical antifungal agents; Terbinafine, Miconazole, Enilconazole, Ketoconazole as well as combined essential oils (EOs) where they were tested for their curative antifungal effects. Results showed that topical treatment with combined essential oils have had a very effective antifungal curative effect. Also, antifungal agents showed clinical improvement of skin lesions in the following order: combined essential oils, Enilconazole, Miconazole, Terbinafine and Ketoconazole. The results also proved that local treatment appears to be effective in most cases with no need for systemic treatment.

A two- year-old Sphynx cat, an unneutered female with multiple erythematous papules with hyperpigmentation was presented. In skin biopsy, in the dermis, well differentiated monomorphic mast cells were found. Fungal culture was positive for Microsporum canis. Diagnosis of urticaria pigmentosa following M. canis infection was made. The animal was successfully treated with itraconazole orally and shampoo containing chlorhexidine and miconazole. To the authors’ knowledge, this is the first reported case of urticaria pigmentosa following the dermatophyte infection in a Sphynx cat.

A chiral separation method coupled with capillary electrophoresis (CE) analysis for ketoconazole and miconazole enantiomers using chiral selectors such as β-cyclodextrin (β-CD) and hydroxypropyl-β-CD (HP-β-CD) was developed in this study, which included the optimisation, validation and application of the method on the antifungal cream samples. The formation of inclusion complex between the hosts (β-CD and HP-β-CD) and guests (ketoconazole and miconazole) were compared and analysed using ultraviolet-visible spectrophotometry, nuclear magnetic resonance (NMR) spectroscopy and molecular docking methods. Results from the study showed that in a concentration that ranged between 0.25 and 50 mg L-1 , the linear calibration curves of each enantiomer had a high coefficient of regression (R2 > 0.999), low limit of detection (0.075 mg L-1 ) and low limit of quantification (0.25 mg L-1 ). The relative standard deviation (RSD) of the intraday and interday analyses ranged from 0.79% to 8.01% and 3.30% to 11.43%, respectively, while the recoveries ranged from 82.0% to 105.7% (RSD < 7%, n = 3). The most probable structure of the inclusion complexes was proposed based on the findings from the molecular docking studies conducted using the PatchDock server.

Background Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. Objectives The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. Design Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. Setting The randomised controlled trial was conducted in 18 neonatal intensive care units in England. Participants Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). Interventions The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin–miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. Main outcome measure Study 1 – time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 – cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 – risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. Results Study 1, clinical effectiveness – 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation – the mean cost of babies’ hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23–27 and 28–32 weeks’ gestation, respectively. Study 3, generalisability analysis – risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. Limitations The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. Conclusions No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin–miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child’s life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. Trial registration Current Controlled Trials ISRCTN81931394. Funding This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.

This study assessed the effects of chitosan (CS) on microcosm biofilms derived from saliva of patients with Candida-associated denture stomatitis.Five removable denture wearers with denture stomatitis were included in the study. The minimum inhibitory concentration (MIC) of CS against clinical isolates of Candida albicans was determined according to the broth microdilution method. Pooled saliva from the donors was used as an inoculum for the formation of biofilms, which were developed during 72 h on acrylic surfaces in the Amsterdam Active Attachment model. The biofilms were then treated with different concentrations of CS, and the antibiofilm effects were evaluated through the quantification of colony-forming units (CFUs), total biomass (TB), metabolic activity (MA), lactic acid production (LAP), and cell viability (by confocal laser scanning microscopy). Chlorhexidine, miconazole, and nystatin were tested as positive controls, while the negative control (NC) was the untreated biofilm. Data were analyzed by 1-way ANOVA and Fischer LSD's post hoc test (α=0.05).MIC values of CS ranged from 500 to 800 µg/mL. For CFUs, 2500 µg/mL CS was the most effective treatment in reducing total anaerobes, mutans streptococci, and Lactobacillus spp., significantly differing from the controls. For C. albicans CFUs, CS and positive controls did not differ from each other but led to significant reductions compared to NC. Regarding TB, MA, LAP, and cell viability, 2500 µg/mL CS promoted the greatest reductions compared to NC.CS has similar or superior effects to conventional active principles on important parameters of oral candidiasis microcosm biofilms.The antibiofilm effects of CS show that this compound has great potential to improve the clinical condition of denture stomatitis patients, and formulations containing this natural polymer could be useful for controlling oral candidiasis.

Background The combined mixture of miconazole nitrate (MIC) and nystatin (NYS) has proven its efficiency as a prodigious remedy to cure women’s frequent infections: vaginal mycosis and vaginal candidiasis. Objective A novel green spectrophotometric technique, namely the Fourier self-deconvolution method (FSD), was employed for the quantitative determination of MIC and NYS in their pure and pharmaceutical forms without prior separation. Moreover, the proposed technique was first employed to study the dissolution profile of the cited drugs in their pharmaceutical formulation according to FDA recommendations without excipient interference. Method The FSD method is based on a simple mathematical manipulation of zero-order spectra of the cited drugs, which suffered from severe overlapping, so zero-order spectra of the cited drugs were deconvoluted using the Fourier wavelet function in spectrophotometer software. The deconvoluted amplitudes for MIC and NYS were measured at 255 nm and 320 nm, respectively. Results Linearity ranges were 70–700 µg/mL for MIC and 1–25 µg/mL for NYS. The greenness of the proposed technique was assessed using two assessment tools, namely eco-scale scoring and green analytical procedure index (GAPI), revealing the excellent greenness of this technique. The proposed technique was validated consistent with ICH guidelines and statistically compared to the reported method with no significant differences between them. Conclusions The proposed technique has advantages of being simple, time-saving, and noting need any modification to be suitable for quantitative analysis of MIC and NYS in both pharmaceutical and laboratory mixtures. Highlights An innovative FSD method was developed for quantitative analysis of MIC and NYS in their synthetic and pharmaceutical mixtures and applied for in vitro dissolution testing of their pharmaceutical mixture, producing satisfactory results.

Despite a certain breadth of expertise and simplicity in diagnosis of candidal vaginitis, current monitoring of the etiological disease structure and a variety of drugs for treatment, the problem of therapy for recurrent forms of this nosology is still unresolved. Among the problematic non albicans (C. glabrata, C. kruzei) species, the strains mainly had a dose-dependent sensitivity to the main antimycotics (fluconazole, itraconazole, miconazole, ketoconazole,), i.e. their efficacy in vivo if taken at doses safe for humans is directly associated with the ability of the drug to accumulate in the mucous membrane, creating the necessary concentration for non albicans. In this regard, determining sensitivity of fungi in clinical practice is currently more justified for non albicans species. The studies of recent years arguing against assumptions concerning pathogenesis associated with the biofilm formation by fungi of the genus Candida on the surface of the vaginal mucosa may allow come closer to the pathogenetic substantiation of the use of local and systemic etiotropic therapy. In this case, at least two factors should be taken into account: the yeast fungus may be resistant to the used antimycotic agent, which is characteristic mainly of non-albicans species, especially C. glabrata and C. krusei, and the invasion of the fungus pseudomycelium into the vaginal mucosa. The article discusses the issues of etiotropic therapy for vulvo-vaginal candidiasis based on the current medical data. The authors provide recommendations for the use of systemic and local antimycotics and substantiated the expediency of their separate and combined use in certain clinical situations.

To evaluate the effectiveness of microwave disinfection in treating Candida-associated denture stomatitis (CADS). The PubMed/MEDLINE, Embase, and Scopus databases were searched for reports on randomized clinical trials (RCTs) published in English until May 2020 (PROSPERO CRD42020192062) that evaluated the treatment of CADS by using microwave disinfection. The main outcomes were the improvement of clinical signs and/or the decrease in the residual yeast present on the dentures and palatal mucosa. The mean differences, standard deviations, risk ratio, and 95% confidence interval were calculated by using the random-effects model. Heterogeneity was assessed by using Cochran’s Q test and I2 values. The level of significance was set at α = 0.05. Five RCTs with 245 participants were included. The descriptive investigations demonstrated that microwave disinfection was as effective (p > 0.05) as 0.2% chlorhexidine, 0.02% sodium hypochlorite, and topical nystatin (100.000 IU/mL), and was superior to topical miconazole in treating CADS. The metaanalysis did not show a statistical difference between microwave disinfection and nystatin (100.000 IU/mL) treatment in terms of mycological counts, cure, and recurrence rates (p > 0.05). Microwave disinfection showed comparable results with those of conventional therapies for treating CADS. In addition, treatment with 650 W for 3 min once a week for 14 days had better cost-effect results, indicating both the prevention and treatment of CADS. Our findings provide evidence regarding the treatment of CADS using microwave disinfection, and also indicating the best cost-effective option for this treatment modality.

The rising prevalence of multidrug-resistant hospital-acquired infections has increased the need for new antibacterial agents. In this study, a library of 1586 FDA-approved drugs was screened against A. calcoaceticus, a representative of the Acinetobacter calcoaceticus-baumannii complex. Three compounds were found to have previously undiscovered antibacterial properties against A. calcoaceticus: antifungal Miconazole, anthelminthic Dichlorophen, and Bithionol. These three drugs were tested against a wide range of Gram-positive and Gram-negative bacteria and confirmed to have broad-spectrum antibacterial properties. Combinations of these three drugs were also tested against the same bacteria, and two novel combination therapies with synergistic effects were discovered. In the future, antibacterial properties of these three drugs and two combination therapies will be evaluated against pathogenic bacteria using an animal model.

In the current experimental study, we have synthesised new monocarbonyl curcumin analogues bearing propargyl ether moiety in their structure and evaluated for in vitro antifungal and radical scavenging activity. The antifungal activity was carried out against five human pathogenic fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Most of the curcumin analogues displayed excellent to moderate fungicidal activity when compared with standard drug Miconazole. Also, synthesised analogues exhibited potential radical scavenging activity as compared with standard antioxidant Butylated hydroxyl toluene (BHT). Based on biological data, structure-activity relationship (SAR) were also discussed. Furthermore, in silico computational study was carried out to know binding interactions of synthesised analogues in the active sites of enzyme sterol 14α-demethylase (CYP51).

Background Dermatomycoses are the most common fungal infections in the world affecting a significant part of the human and animal population. The majority of zoophilic infections in humans are caused by Trichophyton mentagrophytes. Currently, the first-line drug for both oral and topical therapy is terbinafine. However, an increasing number of cases that are difficult to be cured with this drug have been noted in Europe and Asia. Resistance to terbinafine and other allylamines is very rare and usually correlated with point mutations in the squalene epoxidase gene resulting in single amino acid substitutions in the enzyme, which is crucial in the ergosterol synthesis pathway. Purpose Here, we report terbinafine-resistant T. mentagrophytes isolates among which one was an etiological factor of tinea capitis in a man and three were obtained from asymptomatic foxes in Poland. Methods We used the CLSI protocol to determine antifungal susceptibility profiles of naftifine, amphotericin B, griseofulvin, ketoconazole, miconazole, itraconazole, voriconazole, and ciclopirox. Moreover, the squalene epoxidase gene of the terbinafine-resistant strains was sequenced and analysed. Results In the genomes of all four resistant strains exhibiting elevated MICs to terbinafine (16 to 32 µg/ml), single-point mutations leading to Leu393Phe substitution in the squalene epoxidase enzyme were revealed. Among the other tested substances, a MIC50 value of 1 µg/ml was shown only for griseofulvin. Conclusion Finally, our study revealed that the terbinafine resistance phenomenon might not be acquired by exposure to the drug but can be intrinsic. This is evidenced by the description of the terbinafine-resistant strains isolated from the asymptomatic animals.

Azole antifungal drugs are commonly used in antifungal chemotherapy. Antibacterial effects of some topical antifungals, such as miconazole and econazole, have lately been revealed, which suggests a promising venue in antimicrobial chemotherapy. In this study, we tested an in-house azole collection with antifungal properties for their antibacterial activity to identify dual-acting hits using the broth microdilution method. The in vitro screen yielded a number of potent derivatives against gram-positive bacteria, Enterococcus faecalis and Staphylococcus aureus. Compound 73's minimum inhibitory concentration (MIC) value less than 1 μg/ml against S. aureus; however, none of the compounds showed noteworthy activity against methicillin-resistant S. aureus (MRSA). All the active compounds were found safe at their MIC values against the healthy fibroblast cells in the in vitro cytotoxicity test. Molecular docking studies of the most active compounds using a set of docking programs with flavohemoglobin (flavoHb) structure, the proposed target of the azole antifungals with antibacterial activity, presented striking similarities regarding the binding modes and interactions between the tested compounds and the antifungal drugs with crystallographic data. In addition to being noncytotoxic, the library was predicted to be drug-like and free of pan-assay interference compounds (PAINS). As a result, the current study revealed several potential azole derivatives with both antifungal and antibacterial activities. Inhibition of bacterial flavoHb was suggested as a possible mechanism of action for the title compounds.