Treatment Of Fungal Skin Infections Research Articles

Anti-Dermatophyte and Anti-Malassezia Activity of Extracts Rich in Polymeric Flavan-3-ols Obtained from Vitis vinifera Seeds.

Several human skin diseases are associated with fungi as dermatophytes and Malassezia. Skin mycoses are increasing and new alternatives to conventional treatments with improved efficacy and/or safety profiles are desirable. For the first time, the anti-dermatophytes and the anti-Malassezia activities of Vitis vinifera seed extracts obtained from different table and wine cultivars have been evaluated. Geometric minimal inhibitory concentration ranged from 20 to 97 µg/mL for dermatophytes and from 32 to 161 µg/mL for Malassezia furfur. Dried grape seed extracts analyzed by HPLC/DAD/ESI/MS showed different quali-quantitative compositions in terms of monomeric and polymeric flavan-3-ols. The minimal inhibitory concentrations for Trichophyton mentagrophytes and for M. furfur were inversely correlated with the amount of the polymeric fraction (r = -0.7639 and r = -0.7228, respectively). Differently, the antifungal activity against T. mentagrophytes was not correlated to the content of flavan-3-ol monomers (r = 0.2920) and only weakly correlated for M. furfur (r = -0.53604). These results suggest that extracts rich in polymeric flavan-3-ols, recovered from V. vinifera seeds, could be used for the treatment of skin fungal infections. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of chitosan coating on microemulsion for effective dermal clotrimazole delivery

Clotrimazole (CTZ) is a broad spectrum antimycotic agent known to be very effective locally for the treatment of fungal skin infections. The aim of this study was to study the effect of chitosan-coated microemulsion (CME) for topical delivery of CTZ and also evaluate its in vitro antifungal efficacy, ex vivo permeation and retention ability on the skin surface. The pseudo-ternary phase diagrams were developed using clove oil as oil phase, Tween 80 and propylene glycol as surfactant and co-surfactant, respectively, and distilled water as aqueous phase. CME was prepared by the drop wise addition of chitosan solution to the optimized microemulsion. Physicochemical parameters (globule size, zeta potential, drug content, viscosity and pH) and in vitro release of CME were studied. The in vitro antifungal efficacy of CME and ME was studied by cup-plate method against Candida albicans. Ex vivo drug permeation study was also carried out in a modified diffusion cell, using rat skin. The developed CME displayed an average globule size less than 50 nm and a positive surface charge, acceptable physico-chemical behavior, and exhibited sustained drug release in in vitro study. In in vitro anti-fungal study, CME showed greater values of zone of inhibition as compared to ME due to its prolonged action as well as fungistatic nature of chitosan. In ex vivo study, CME showed better retention and sustained permeation property than ME due to the mucoadhesive property of chitosan. These results suggest that positively charged CMEs could be used as novel topical formulation for its ability to retain on the skin and its ability to sustain the release of the drug.

In Vitro Antimicrobial Photodynamic Therapy Against Trichophyton mentagrophytes Using New Methylene Blue as the Photosensitizer

Introduction and objectivesAntimicrobial photodynamic therapy combines the use of a photosensitizing drug with light and oxygen to eradicate pathogens. Trichophyton mentagrophytes is a dermatophytic fungus able to invade the skin and keratinized tissues. We have investigated the use of new methylene blue as the photosensitizing agent for antimicrobial photodynamic therapy to produce the in vitro inactivation of T mentagrophytes. Material and methodsA full factorial design was employed to optimize the parameters for photoinactivation of the dermatophyte. The parameters studied were new methylene blue concentration, contact time between the photosensitizing agent and the fungus prior to light treatment, and the fluence of red light (wavelength, 620–645nm) applied. ResultsThe minimum concentration of new methylene blue necessary to induce the death of all T. mentagrophytes cells in the initial suspension (approximate concentration, 106 colony forming units per milliliter) was 50μM for a fluence of 81J/cm2 after a contact time of 10minutes with the photosensitizing-agent. Increasing the concentration to 100μM allowed the fluence to be decreased to 9J/cm2. ConclusionsComparison of our data with other published data shows that the susceptibility of T. mentagrophytes to antimicrobial photodynamic therapy with new methylene blue is strain-dependent. New methylene blue is a photosensitizing agent that should be considered for the treatment of fungal skin infections caused by this dermatophyte.

Terapia fotodinámica antimicrobiana in vitro aplicada sobre Trichophyton mentagrophytes con nuevo azul de metileno como fotosensibilizador

Introduction and objectivesAntimicrobial photodynamic therapy combines the use of a photosensitizing drug with light and oxygen to eradicate pathogens. Trichophyton mentagrophytes is a dermatophytic fungus able to invade the skin and keratinized tissues. We have investigated the use of new methylene blue as the photosensitizing agent for antimicrobial photodynamic therapy to produce the in vitro inactivation of T mentagrophytes. Material and methodsA full factorial design was employed to optimize the parameters for photoinactivation of the dermatophyte. The parameters studied were new methylene blue concentration, contact time between the photosensitizing agent and the fungus prior to light treatment, and the fluence of red light (wavelength, 620–645nm) applied. ResultsThe minimum concentration of new methylene blue necessary to induce the death of all T. mentagrophytes cells in the initial suspension (approximate concentration, 106 colony forming units per milliliter) was 50μM for a fluence of 81J/cm2 after a contact time of 10minutes with the photosensitizing-agent. Increasing the concentration to 100μM allowed the fluence to be decreased to 9J/cm2. ConclusionsComparison of our data with other published data shows that the susceptibility of T. mentagrophytes to antimicrobial photodynamic therapy with new methylene blue is strain-dependent. New methylene blue is a photosensitizing agent that should be considered for the treatment of fungal skin infections caused by this dermatophyte.

Primary care physicians’ knowledge and self-perception of competency in dermatology: An evaluation study from Yemen

AbstractPurpose: Dermatologists recognize the role of primary care clinics where 6–7% of visits are for skin complaints and are seen by primary care physicians (PCPs). Previous studies investigated PCPs’ competency in dermatology but few studies investigated PCPs’ knowledge and self-perception of competency in dermatology which is the main aim for the current study. Methods: A cross-sectional study was conducted and 40 PCPs were recruited from nine randomly selected clinics in Aden, Yemen during April–May 2014. Findings: The majority (47.5%) of PCPs perceived their competencies in diagnosing and treating skin diseases as average. There were no significant differences in classification scores of skin lesions among PCPs by self-perception competency group “Good, Average, Bad”. Half of the PCPs identified correctly that topical antifungal monotherapy is superior to topical antifungal/corticosteroid combinations for the treatment of fungal skin infections. Only 12.5% of PCPs correctly identified that glucocor...

Recent advances in topical formulation carriers of antifungal agents.

Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal infections. Examples of these newer carriers include micelles, lipidic systems such as solid lipid nanoparticles and nanostructured lipid carriers, microemulsions and vesicular systems such as liposomes, niosomes, transfersomes, ethosomes, and penetration enhancer vesicles.

Development of solid lipid nanoparticles based controlled release system for topical delivery of terbinafine hydrochloride

The study describes the development and evaluation of solid lipid nanoparticles (SLNs) of terbinafine hydrochloride (TH) for sustained release and skin targeting. TH-loaded SLNs were prepared by solvent-injection technique and optimized using 33 full-factorial design. Effect of drug:lipid ratio, surfactant concentration and volume of organic solvent were studied on % entrapment efficiency (%EE) and particle size (PS). The optimum formulation based on desirability (0.945) exhibited %EE of 73.74% and PS of 300nm. Optimized SLNs were incorporated into Carbopol gel and evaluated for drug content, pH, in vitro release, ex vivo retention, in vivo pharmacodynamic and stability studies. Drug release from SLNs dispersion followed Korsmeyer–Peppas model, indicating Fickian drug release, while that from the gel followed Higuchi model. The ex vivo studies through rat abdominal skin indicated skin retention ability of SLNs as compared to commercial product. In vivo pharmacodynamic studies showed that the SLNs based gel reduced fungal burden of Candida albicans in rats as compared to commercial product in shorter duration of time. The SLNs dispersion and gel exhibited physicochemical stability under refrigeration upto 3months. It was concluded that SLNs incorporated Carbopol gel had skin targeting ability and may serve as a promising carrier in treatment of fungal skin infections.

Antifungal activity of Andrographis paniculata extracts and active principles against skin pathogenic fungal strains in vitro

Context: Andrographis paniculata Nees. (Acanthaceae) is an annual herbaceous plant widely cultivated in southern Asia, China, and Europe. It is used in the treatment of skin infections in India, China, and Malaysia by folk medicine practitioners.Objective: Antifungal activity of the whole plant extracts and isolation of active principles from A. paniculata were investigated.Materials and methods: Dichloromethane (DCM) and methanol (MEOH) extracts of A. paniculata whole plant were screened for their antifungal potential using broth microdilution method in vitro against seven pathogenic fungal species responsible for skin infections. Active principles were detected through bioguided assays and isolated using chromatography techniques. Structures of compounds were elucidated through spectroscopy techniques and comparisons were made with previously reported data for similar compounds.Results: DCM extract revealed lowest minimum inhibitory concentration (MIC) value (100 μg/mL) against Microsporum canis, Candida albicans, and Candida tropicalis, whereas MEOH extract revealed lowest MIC (150 µg/mL) against C. tropicalis and Aspergillus niger. DCM extract showed lowest minimum fungicidal concentration (MFC) value (250 µg/mL) against M. canis, C. albicans, C. tropicalis and A. niger, whereas MEOH extract showed lowest MFC (250 µg/mL) against Trichophyton mentagrophytes, Trichophyton rubrum, M. canis, C. albicans, C. tropicalis and A. niger. Bioassay guided isolation from DCM and MEOH extract afforded 3-O-β-d-glucosyl-14-deoxyandrographiside, 14-deoxyandrographolide, and 14-deoxy-11,12-didehydroandrographolide as antifungal compounds. The lowest MIC (50 µg/mL) and MFC (50 µg/mL) was exerted by 14-deoxyandrographolide on M. canis.Discussion and conclusion: This is first report on the isolation of antifungal substances through bioassay-guided assay from A. paniculata. Our finding justifies the use of A. paniculata in folk medicines for the treatment of fungal skin infections.

Influence of various lipid core on characteristics of SLNs designed for topical delivery of fluconazole against cutaneous candidiasis

Dermal delivery of fluconazole (FLZ) is still a major limitation due to problems relating to control drug release and achieving therapeutic efficacy. Recently, solid lipid nanoparticles (SLNs) were explored for their potential of topical delivery, possible skin compartments targeting and controlled release in the skin strata. The retention and accumulation of drug in skin is affected by composition of SLNs. Hence, the aim of this study was to develop FLZ nanoparticles consisted of various lipid cores in order to optimize the drug retention in skin. SLNs were prepared by solvent diffusion method and characterized for various in vitro and in vivo parameters. The results indicate that the SLNs composed of compritol 888 ATO (CA) have highest drug encapsulation efficiency (75.7 ± 4.94%) with lower particle size (178.9 ± 3.8 nm). The in vitro release and skin permeation data suggest that drug release followed sustained fashion over 24 h. The antifungal activity shows that SLNs made up of CA lipid could noticeably improve the dermal localization. In conclusion, CA lipid based SLNs are represents a promising carrier means for the topical treatment of skin fungal infection as an alternative to the systemic delivery of FLZ.

In Vitro Killing of Clinical Fungal Strains by Low-Temperature Atmospheric-Pressure Plasma Jet

Plasma medicine is an expanding focus and offers new aspects of therapy combining potent physical partial efficacies, like such as ultraviolet, infrared, and reactive species and particles, and nowadays, many successful treatments of different illnesses have been described. Fungal skin and nail infections pose significant therapeutic and economical problems. To test the plasma susceptibility of clinical strains of the most frequently encountered fungal species involved in dermatomycosis, clinical isolates of Trichophyton interdigitale, Trichophyton rubrum, Microsporum canis, and Candida albicans were irradiated by a cold atmospheric pressure plasma jet. Punctual plasma irradiation eradicated fungal growth of all species with the largest inactivation zones with most progress in the first 15 s of treatment, treating C. albicans and least progress in that of , the lowest being M. canis. No isolate exhibited resistance to plasma treatment. Plasma treatment also completely eradicated reproductive fungal elements of T. interdigitale in dandruff of patients with tinea pedis ex vivo and in the environment in contaminated shoes. Accordingly, cold plasma seems suited to antifungal in vivo treatment of fungal skin infections and decontamination of environmental infective material.

Transdermal iontophoretic delivery of terbinafine hydrochloride: Quantitation of drug levels in stratum corneum and underlying skin

The objective of this study was to determine the effect of iontophoresis on the delivery of terbinafine hydrochloride (4%, w/w) into and across hairless rat skin. In vitro skin uptake and permeation studies were performed using Franz diffusion cells. Anodal iontophoresis was applied for 1 h at current densities of 0.2, 0.3 and 0.4 mA/cm 2. In addition, iontophoresis was applied for 15, 30, 45 and 60 min. Studies were conducted in which the formulation was either removed or left in contact with the skin following iontophoresis and then passive delivery was assessed 23 h later. Tape stripping and skin extraction were performed to quantify drug levels in the stratum corneum and the underlying skin, respectively. The samples were analyzed using HPLC. The amount of drug delivered into the stratum corneum following iontophoresis was not significantly different from the amount delivered passively ( p > 0.05). However, drug levels in the underlying skin were significantly higher for the iontophoretic group. The amount of terbinafine delivered into the skin layers was influenced by current density and duration of current application. Leaving the drug formulation in contact with the skin during the post-iontophoretic period had a significant effect on drug levels delivered into skin layers. Iontophoresis enhanced the delivery of terbinafine hydrochloride into the skin layers and, therefore, may be used to improve the treatment of skin fungal infections.

Physically Cross-Linked Polyvinyl Alcohol for the Topical Delivery of Fluconazole

The aim of this study was to develop fluconazole in an ultrapure polyvinyl alcohol (PVA) hydrogel able to deliver the drug in a sustained release pattern for local treatment of skin fungal infections. The topical fluconazole hydrogels were prepared using PVA hydrogels physically cross-linked by freeze–thaw technique. Polyethylene glycol (PEG) was added as a hydrophilic excipient as a release enhancer of fluconazole. The effects of PVA molecular weight, PEG molecular weight, and PEG concentration were studied using a 2 × 4 × 2 factorially designed experiment. The selected fluconazole hydrogel proved to be physically stable over a period of 6 months and to be effective in the topical treatment of cutaneous candidiasis. Therefore, it could be concluded that the formula composed of 10% PVA 205000 and 1.5% PEG 4000 and 2% fluconazole and prepared by three cycles of freezing, and thawing is very promising in the local treatment of skin fungal infection as an alternative to the systemic use of fluconazole.

Comparative Study of 2% Sertaconazole Solution and Cream Formulations in Patients with Tinea Corporis, Tinea Pedis Interdigitalis, or a Corresponding Candidosis

Based on the results of numerous preclinical and clinical studies, sertaconazole can be considered a safe and effective drug for the treatment of fungal skin infections. The objective of the study was to compare the efficacy of a solution containing 2% sertaconazole with the well established 2% sertaconazole cream formulation in patients with tinea corporis, tinea pedis interdigitalis, or a corresponding candidosis. This was a prospective, open-label, randomized, controlled, parallel-group, multicenter, noninferiority therapy study. Patients received either sertaconazole solution or cream twice daily for 28 days. The full analysis set comprised 160 patients in the solution group and 153 patients in the cream group. The primary efficacy parameter was a combination of culture test result and total clinical score. Efficacy was defined by eradication of the pathogen and reduction of the total clinical score between pretreatment and the final visit. Efficacy was documented in 90.6% of patients using the solution and 88.9% of those using the cream (full analysis set). No adverse events occurred. Solution and cream formulations of 2% sertaconazole applied for 28 days were associated with comparable efficacy and safety in the treatment of fungal skin infections.

Griseofulvin Enhances the Effect of Aminolevulinic Acid–Based Photodynamic Therapy in Vitro

In this study, we investigated whether or not griseofulvin (GF), which is an antimycotic widely used for the oral treatment of skin fungal infections, enhanced the effect of aminolevulinic acid-based photodynamic therapy (ALA-PDT) in vitro, using several tumor cell lines. A human squamous cell carcinoma line (KB), two human osteosarcoma cell lines from mandible (HOSM-1, HOSM-2), and the human gingiva-derived fibroblast line (HF), representing normal cells, were used. GF enhancement of ALA-PDT was evaluated by comparing the effect of ALAin combination with GF to the effect of ALAalone (GF enhancement rate of ALA-PDT). Also, the effect of GF on intracellular accumulation of protoporphyrin IX (PpIX) was evaluated by comparing the intracellular accumulation of PpIX in the ALA and GF combined treatment with that of ALA treatment alone (pGF enhancement rate of intracellular PpIX). GFenhancement rate of ALA-PDT was 2.51 in KB cells, and 1.65 and 1.27 in HOSM-1 and HOSM-2 cells, respectively. GF enhancement rates of intracellular PpIX were 1.94 in KB cells, 1.53 in HOSM-1 cells, and 1.19 in HOSM-2 cells. GF enhancement rate of intracellular PpIX followed the same trends as the levels of GF enhancement rate of ALA-PDT in the different cell types. For HF, a large effect was not revealed in this study. The present study, although preliminary, strongly suggests that concomitant treatment with ALAand GF may be very useful to enhance the effect of ALA-PDT.

Antidermatophyte activity of ether extract of Nigella sativa and its active principle, thymoquinone

The antifungal activity of ether extract of Nigella sativa seed and its active principle thymoquinone was tested against eight species of dermatophytes: four species of Trichophyton rubrum and one each of Trichophyton interdigitale, Trichophyton mentagrophytes, Epidermophyton floccosum and Microsporum canis. Agar diffusion method with serial dilutions of ether extract of Nigella sativa, thymoquinone and griseofulvin was employed. The incubation was carried out at 30 °C for 14 days. The diameter of fungal colonies and the percentage inhibition of the fungal growth at each dilution were determined, taking those of the controls as 100%. The minimum inhibitory concentration (MIC) was considered as the minimum concentration of the drug, which inhibited 80–100% of the fungal growth. The MICs of the ether extract of Nigella sativa and thymoquinone were between 10 and 40 and 0.125 and 0.25 mg/ml, respectively, while those of griseofulvin ranged from 0.00095 to 0.0155 mg/ml. These results denote the potentiality of Nigella sativa as a source for antidermatophyte drugs and support its use in folk medicine for the treatment of fungal skin infections.

An alternative treatment for pityriasis versicolor, tinea cruris, tinea corporis and tinea faciei with topical application of honey, olive oil and beeswax mixture: an open pilot study

Objective: To evaluate the possible role of honey, olive oil and beeswax in the treatment of skin fungal infections. Patients and methods: Thirty-seven patients with pityriasis versicolor, tinea cruris, tinea corporis and tinea faciei were studied. After clinical evaluation of redness, scaling, pruritis and burning/pain sensation and mycological assessment, honey mixture containing honey, olive oil and beeswax (1:1:1) was applied to the lesions three times daily for a maximum of 4 weeks. Results: Clinical response was obtained in 86% of patients with pityriasis versicolor, 78% of patients with tinea cruris and in 75% of patients with tinea corporis. Mycological cure was obtained in 75, 71 and 62% of patients with PV, tinea cruris and tinea corporis, respectively. The patient with tinea faciei showed clinical and mycological cure 3 weeks after commencement of therapy. Conclusion: Honey mixture may have place in the management of these skin conditions and rigorous, controlled trials are justified.

Oral terbinafine (Lamisil) in the short-term treatment of fungal infections of the skin: results of a post-marketing surveillance study.

Oral terbinafine (Lamisil, Novartis Pharma AG, Basel, Switzerland) is an effective therapy for fungal infections of the skin and nails. A post-marketing surveillance study was undertaken to evaluate the clinical efficacy and safety of oral terbinafine. A total of 454 patients with clinically and mycologically confirmed superficial fungal infections of the skin were enrolled from 79 dermatology clinics. Patients received oral terbinafine (250 mg day-1) for 2 weeks. Specific signs and symptoms were assessed by standard questionnaire before, immediately after, and 4 weeks after treatment. Observed improvements in patients after 2 weeks treatment were: erythema 81%, blistering 33%, exudation 50%, scaling 89%, pruritus 83%. After 4 weeks treatment, erythema was absent in 85% of patients, blistering and exudation in 99.7%, scaling in 82%, and pruritus in 94%. Overall clinical efficacy was assessed as good to excellent in 97% of patients. Adverse effects--mainly gastrointestinal and minor skin rashes--were reported in 5.3% of patients. The results of this study confirm that oral terbinafine is safe and highly effective for the short-term treatment of fungal skin infections.

Dermatophytomycoses in children in rural Kenya: the impact of primary health care.

In a survey of 5780 children from 13 schools in rural Kisumu District (western Kenya) in 1993, a prevalence rate of dermatophytomycoses of 10.1% was found. Three-quarters of the affected children suffered from tinea capitis (prevalence rate 7.8%), caused by Microsporum audouinii var. langeronii, Trichophyton violaceum and Microsporum canis. In 1994, a dermatology programme within the primary health care system was started. Twelve community health workers (CHWs), trained in diagnosis and treatment of the most common skin diseases, carried out regular school visits once a week. All dermatophytomycoses, dry forms of tinea capitis included, were treated locally with Whitfield's ointment. In 1995 the prevalence rate of fungal skin infections in the same schools was found to be 9.3%; the difference to 1993 was not significant. Only tinea capitis, with a prevalence rate of 5.8%, showed a significant reduction (P < 0.05). Altogether, a distinctive improvement regarding the extent and the severity of dermatophytomycoses could be noticed. In the cultures from tinea capitis, Microsporum canis was not found to be present. Trained community health workers are capable of the diagnosis and treatment of fungal skin infections of children in rural areas, which leads to a reduction in the prevalence of tinea capitis.

Electroanalytical and Bacterial Effect on N-(5-Nitro-2-Furfurylidine)3-Amino-2-Oxazolidone) (Furazolidone) and its Metal Complexes

Abstract A number of metal-furazolidone complexes have been synthesized and screened for antibacterial and antifungal activity. The study reveals the remarkable efficacy of Co(II), Cu(II), Zn(II) and Cd(II) complexes against the various strains of bacteria and fungi, viz., Pseudomonas mangiferae, Bacillus pumillus, and Salmonella typhi suggest a strong possibility of its application for the treatment of fungal skin infections. The most striking feature has been the activity of Cu-furazolidone complex, it was found to be uniformly active against all the strains of bacteria and fungi under study. Electroanalytical findings of these metal furazolidone complexes have also been performed.

Treatment of fungal skin infections: State of the art

The number of cases of mycotic infections are increasing, presenting physicians today with an unprecedented challenge in handling the treatment and prophylactic control of these disorders. The increase in mycotic disorders is due to many factors, such as longer life span, organ transplantation, and the acquired immunodeficiency syndrome. The pharmaceutical industry is providing physicians with newer, more potent drugs to manage mycoses. An overview of current practice in the use of topical and oral agents, especially ketoconazole, are given in the following specific mycoses: tinea capitis, pityriasis versicolor, seborrheic dermatitis, Trichophyton rubrum infections, vaginal candidiasis, and moist intertriginous tineas. The efficacy of ketoconazole in various vehicles and dosage schedules and of traditional agents such as griseofulvin are discussed with relation to each of the mycoses.