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Journal of Obstetrics and Gynaecology :... Dec 2023At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a... (Review)
Review
At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a microsomal cytochrome P450 (CYP) enzyme. Imidazoles and triazoles impair the biosynthesis of ergosterol for the cytoplasmic membrane and lead to the accumulation of 14-α-methyl sterols. The synthetic imidazole miconazole is additionally able to increase intracellular reactive oxygen species, at least in part through inhibition of fungal catalase and peroxidase. This unique feature of miconazole is probably the basis for its fungicidal activity in , in addition to the fungistatic mode of action. Studies show that miconazole is superior to nystatin treatment and demonstrate its impact as one of the best options in managing vulvovaginal candidiasis. Regarding recurrent vulvovaginal candidiasis, several new drugs are currently developed to ensure effective treatment also for this group of patients.
Topics: Female; Humans; Miconazole; Candidiasis, Vulvovaginal; Antifungal Agents; Imidazoles; Nystatin; Candida albicans; Cytochrome P-450 Enzyme System
PubMed: 37029724
DOI: 10.1080/01443615.2023.2195001 -
Acta Crystallographica. Section E,... Feb 2024The crystal structure of the new triclinic polymorph of miconazole {MIC; CHClNO; systematic name:...
The crystal structure of the new triclinic polymorph of miconazole {MIC; CHClNO; systematic name: ()-1-[2-(2,4-di-chloro-benz-yloxy)-2-(2,4-di-chloro-phen-yl)eth-yl]-1-imidazole} is reported and compared with the monoclinic form of solvent-free miconazole previously reported [Kaspiaruk & Chęcińska (2022 ▸). C, 343-350]. A comparison shows a different orientation of imidazole and one di-chloro-phenyl ring between polymorphic mol-ecules. In the crystal structure of the title compound, only weak halogen bonds and C-H⋯π(arene) inter-actions are found. Hirshfeld surface analysis and energy framework calculations complement the comparison of the two polymorphic forms of the miconazole drug.
PubMed: 38333136
DOI: 10.1107/S2056989024000276 -
Polymers Nov 2022The development of semisolid formulations, gels in particular, has raised the attention of scientists more and more over the last decades. Because of their...
The development of semisolid formulations, gels in particular, has raised the attention of scientists more and more over the last decades. Because of their biocompatibility, hydrophilic nature, and capacity of absorbing large quantities of water, hydrogels are still one of the most promising pharmaceutical formulations in the pharmaceutical industry. The purpose of this study is to develop an optimal formulation capable of incorporating a water-poorly soluble active ingredient such as miconazole used in the treatment of fungal infections with and . A D-optimal design was applied to study the relationship between the formulation parameter and the gel characteristics. The independent parameters used in this study were the Carbopol 940 concentration (the polymer used to obtain the gel matrix), the sodium hydroxide amount, and the presence/absence of miconazole. Ten different dependent parameters (Y1-Y10) were evaluated (penetrometry, spreadability, viscosity, and tangential tension at 1 and 11 levels of speed whilst destructuring and during the reorganization of the gel matrix). The consistency of the gels ranged from 23.2 mm (GO2) to 29.6 mm (GM5). The least spreadable gel was GO7 (1384 mm), whilst the gel that presented the best spreadability was GO1 (3525 mm). The viscosity and the tangential stress at the selected levels (1 and 11) varied due to the different compositions of the proposed gels. The gels were also tested for drug content and antifungal activity. All determinations had satisfying results; the drug content was within limits accepted by Ph. Eur. 10 and all formulations containing miconazole exhibited antifungal activity. An optimal formulation with miconazole was attained, consisting of 0.84% Carbopol 940 and 0.32% sodium hydroxide.
PubMed: 36433136
DOI: 10.3390/polym14225011 -
Journal of Neurology, Neurosurgery, and... Sep 1985Cryptococcosis is a systemic fungal disease and meningitis is the most serious complication. The purpose of this study is to define problems related to its diagnosis and...
Cryptococcosis is a systemic fungal disease and meningitis is the most serious complication. The purpose of this study is to define problems related to its diagnosis and treatment. This is a retrospective analysis of 25 patients admitted from January 1978 to December 1981. All patients had cryptococcal neoformans meningitis proven by culture of cerebrospinal fluid. One patient had a predisposing illness, being on immunosuppressant therapy after a renal transplant 2 years ago. A progressively severe headache of recent onset was the most striking presentation. Fever was frequently absent as a symptom. Cranial nerve palsies were commonly seen. Impairment of consciousness and areflexia signified a poor prognosis as all four patients who died early in the course of treatment were comatose and two of them were areflexic on admission. In newly suspected cases at least 3 separate lumbar punctures are recommended as initial smears or cultures may be negative. Cerebral CT scans were abnormal in 12 patients and those with cerebral oedema or hydrocephalus had a poorer prognosis. Combined amphotericin B and 5-fluorocytosine therapy was the treatment of choice. If there is no relapse 3 years after completion of treatment, patients are considered as cured. Positive smears may remain for years after completion of treatment and retreatment is only indicated if the cultures are positive. Twenty patients are alive today and none of them have relapsed. One patient had vasculitis of both anterior cerebral arteries as a result of cryptococcal meningitis.
Topics: Adolescent; Adult; Aged; Amphotericin B; Child; Cryptococcosis; Flucytosine; Follow-Up Studies; Garlic; Humans; Ketoconazole; Meningitis; Miconazole; Middle Aged; Plant Extracts; Plants, Medicinal
PubMed: 4045478
DOI: 10.1136/jnnp.48.9.853 -
Journal of Fungi (Basel, Switzerland) Aug 2022A broad range of topical antifungal formulations containing miconazole or terbinafine as actives are commonly used as efficacious choices for combating fungal skin... (Review)
Review
A broad range of topical antifungal formulations containing miconazole or terbinafine as actives are commonly used as efficacious choices for combating fungal skin infections. Their many benefits, owing to their specific mechanism of action, include their ability to target the site of infection, enhance treatment efficacy and reduce the risk of systemic side effects. Their proven efficacy, and positioning in the treatment of fungal skin infections, is enhanced by high patient compliance, especially when appropriate vehicles such as creams, ointments and gels are used. However, inflammation as a result of fungal infection can often impede treatment, especially when combined with pruritus (itch), an unpleasant sensation that elicits an urge to scratch. The scratching that occurs in response to pruritus frequently accelerates skin damage, ultimately aggravating and spreading the fungal infection. To help overcome this issue, a topical antifungal-corticosteroid combination consisting of miconazole or terbinafine and corticosteroids of varying potencies should be used. Due to their inherent benefits, these topical antifungal-corticosteroid combinations can concomitantly and competently attenuate inflammation, relieve pruritus and treat fungal infection.
PubMed: 36012800
DOI: 10.3390/jof8080812 -
Pharmaceutics Feb 2024This research aimed to develop miconazole-based microemulsions using oleic acid as a natural lipophilic phase and a stabilizer mixture comprising Tween 20 and PEG 400 to...
This research aimed to develop miconazole-based microemulsions using oleic acid as a natural lipophilic phase and a stabilizer mixture comprising Tween 20 and PEG 400 to solubilize miconazole as an antifungal agent known for its activity in oral candidiasis and to improve its bioavailability. The formulation and preparation process was combined with a mathematical approach using a 2-full factorial plan. Fluid and gel-like microemulsions were obtained and analyzed considering pH, conductivity, and refractive index, followed by extensive analyses focused on droplet size, zeta potential, rheological behavior, and goniometry. In vitro release tests were performed to assess their biopharmaceutical characteristics. Independent variables coded X-Oleic acid (%, /), X-Tween 20 (%, /), and X-PEG 400 (%, /) were analyzed in relationship with three main outputs like mean droplet size, work of adhesion, and diffusion coefficient by combining statistical tools with response surface methodology. The microemulsion containing miconazole base-2%, oleic acid-5%, Tween 20-40%, PEG 400-20%, and water-33% exhibited a mean droplet size of 119.6 nm, a work of adhesion of 71.98 mN/m, a diffusion coefficient of 2.11·10 cm/s, and together with remarked attributes of two gel-like systems formulated with higher oil concentrations, modeled the final optimization step of microemulsions as potential systems for buccal delivery.
PubMed: 38399325
DOI: 10.3390/pharmaceutics16020271 -
Iranian Journal of Otorhinolaryngology Jan 2022Fungal otitis extern or otomycosis, is common worldwide, and resistance of fungal organisms to antifungal drugs has been reported in otomycosis and other fungal...
INTRODUCTION
Fungal otitis extern or otomycosis, is common worldwide, and resistance of fungal organisms to antifungal drugs has been reported in otomycosis and other fungal infections. This study aimed to evaluate the clinical efficacy of sertaconazole versus placebo, as well as miconazole and clotrimazole topical creams in otomycosis patients.
MATERIALS AND METHODS
In this double-blinded clinical trial, 138 otomycosis patients (230 ears) were evaluated in four groups. After the first session of the ear canal debridement and irrigation with acetic acid 2% solution, the patients were treated with either A) sertaconazole 2% cream, B) miconazole 2% cream, C) clotrimazole 2% cream, or D) placebo. The results of clinical evaluations and response to treatment (complete, partial, and no response) were recorded at the time of the first visit and by the end of the first, second, and fourth weeks of treatment. A p-value less than 0.05 was considered statistically significant.
RESULTS
Response results to treatments, ear itching, aural fullness, otalgia, and otorrhea revealed significant differences in either group A or groups B and C, compared to the placebo group (P<0.05). Considering both complete and partial responses together, the sertaconazole group showed a 96.43% response rate. For complete response, miconazole revealed better results, compared to the other two creams; however, the differences for the therapeutic outcomes were not statistically significant. No adverse reactions were observed in the study groups.
CONCLUSIONS
Sertaconazole had comparable results with miconazole and clotrimazole in the treatment of otomycosis, and especially if complete and partial responses were considered together, it was more efficacious than miconazole and clotrimazole creams.
PubMed: 35145933
DOI: 10.22038/IJORL.2021.54805.2872 -
Brazilian Journal of Microbiology :... Mar 2022Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S. aureus strains, there is a need for...
Staphylococcus aureus is a primary cause of hospital and community-acquired infections. With the emergence of multidrug-resistant S. aureus strains, there is a need for new drugs discovery. Due to the poor supply of new antimicrobials, targeting virulence of S. aureus may generate weaker selection for resistant strains, anti-virulence agents disarm the pathogen instead of killing it. In this study, the ability of the FDA-approved drugs domperidone, candesartan, and miconazole as inhibitors of S. aureus virulence was investigated. The effect of tested drugs was evaluated against biofilm formation, lipase, protease, hemolysin, and staphyloxanthin production by using phenotypic and genotypic methods. At sub-inhibitory concentrations, candesartan, domperidone, and miconazole showed a significant inhibition of hemolysin (75.8-96%), staphyloxanthin (81.2-85%), lipase (50-65%), protease (40-64%), and biofilm formation (71.4-90%). Domperidone and candesartan have similar activity and were more powerful than miconazole against S. aureus virulence. The hemolysins and lipase inhibition were the greatest under the domperidone effect. Candesartan showed a remarkable reduction in staphyloxanthin production. The highest inhibitory effect of proteolytic activity was obtained with domperidone and candesartan. Biofilm was significantly reduced by miconazole. Expression levels of crtM, sigB, sarA, agrA, hla, fnbA, and icaA genes were significantly reduced under candesartan (68.98-82.7%), domperidone (62.6-77.2%), and miconazole (32.96-52.6%) at sub-MIC concentrations. Candesartan showed the highest inhibition activity against crtM, sigB, sarA, agrA, hla, and icaA expression followed by domperidone then miconazole. Domperidone showed the highest downregulation activity against fnbA gene. In conclusion, candesartan, domperidone, and miconazole could serve as anti-virulence agents for attenuation of S. aureus pathogenicity.
Topics: Anti-Bacterial Agents; Benzimidazoles; Biofilms; Biphenyl Compounds; Domperidone; Humans; Methicillin-Resistant Staphylococcus aureus; Miconazole; Staphylococcal Infections; Staphylococcus aureus; Tetrazoles; Virulence
PubMed: 34773629
DOI: 10.1007/s42770-021-00655-4 -
Frontiers in Microbiology 2020Cutaneous mycoses, particularly tinea pedis caused by , are commonly known infections in humans. They are still considered as a major public health problem worldwide...
Cutaneous mycoses, particularly tinea pedis caused by , are commonly known infections in humans. They are still considered as a major public health problem worldwide affecting the quality of life due to prolonged period of treatment and development of drug resistance, which leads to recurrence of infections. The objective of our study was to assess the effectiveness of miconazole in the presence and absence of urea, as a penetration enhancer, against and to formulate both of them in a water-soluble film to be applied topically for the purpose of treating tinea pedis caused by this fungus. Drug combination revealed synergism where miconazole minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) (0.5 and 1 mg/L) were considerably declined to 0.001 and 0.004 mg/L, respectively, when combined with 20% urea. This enhanced drug interaction activity against the test strain was explained by the alterations raised on the morphology and ultrastructures observed microscopically. Minimal fungicidal dose of miconazole/urea combination displayed plasmolysis and shrink cytoplasm; however, necrotic cells with punctured walls and degraded cytoplasmic content were observed at high fungicidal dose. Water-soluble films, prepared using increasing values of miconazole MFC and urea, were transparent, smooth, uniform, and flexible. Their physicochemical characters showed homogeneity in weight, thickness, drug content, and folding endurances with normal surface pH values, indicating the reproducibility of the preparation method. The novel simulation model for the film mechanism of action supported the idea and the suggested application method of the new dosage form. Evaluation of these films was carried using disk diffusion assay as well as using guinea pig dermatophytosis model. The assessment revealed an increase in the inhibition zone diameters in a concentration-dependent manner upon using 10 or 20% of urea combined with miconazole. test showed that combination of 0.004 mg/L miconazole with 20% urea (M + U20) showed the highest efficacy percentage (95.83%), which was statistically superior to the infected untreated control ( < 0.001) in fungal burden reduction as well as improvement in clinical scores ( < 0.001). This work supports the hypothesis and suggests a new promising dosage form for the treatment of infections.
PubMed: 32308646
DOI: 10.3389/fmicb.2020.00385