Discovery of evodiamine derivatives as potential lead antifungal agents for the treatment of superficial fungal infections.

Mycosis, especially superficial fungal infections (SFIs), has been a serious threat to humans in recent years. Evodiamine (EVO), as an effective component of the Traditional Chinese Medicine Evodia rutaecarpa, has good antibacterial effects and low toxicity. In order to find out the potential therapeutic agents against SFIs, a series of EVO derivatives were synthesized and systematic evaluations of antifungal activity were carried out. Among them, compound A7 exhibited great antifungal activity with the values of MIC100 were 38, 38 and 2 µg/mL, respectively, against T. rubrum, T. mentagrophytes and C. albicans, and even stronger than that of ketoconazole (KCZ) with the values of MIC100 were 106, 106 and 3 µg/mL, respectively. Further antifungal evaluations in vitro verified that compound A7 indeed had favorable antifungal activity. Moreover, compound A7 could exert excellent antifungal effect on T. rubrum-infected guinea pigs, suggesting that A7 was an attractive molecule and could be a potential lead compound for the development of anti-fungal agents, and providing a great promising therapeutic strategy for fungal disease.

Factors responsible for difficult to treat superficial fungal infections: A study from a tertiary healthcare centre in India.

BACKGROUND: Recurrent and clinically unresponsive dermatophytosis is being increasingly observed in India. However, there is little information regarding the extent of the problem and the factors responsible for these difficult to treat superficial fungal infections. AIM: To identify factors contributing to difficult to treat recurrent superficial fungal infections. MATERIALS AND METHODS: This prospective cross-sectional study enrolled 105 patients of all age groups presenting with either recurrent or long-standing dermatophyte infection attending the outpatient department of Dermatology, Venerology and Leprosy of Bharati Hospital, Pune, India, between September 2018 and March 2020. Patients were clinically examined, clinical history was taken and questions were asked regarding their current complaints and recorded in a proforma. Data were analysed using the SPSS software package. RESULTS: The males outnumbered females (74.3% vs 25.7%). A strong association was observed between the presence of past history and duration of disease (p = .007). The association of use of topical steroids or keratolytic agents with the duration of disease was statistically significant (p = .022). There was a statistically significant inverse association of duration of disease with dermatologist consultation (p < .001). The association between consultation with non-dermatologist and the duration of disease was statistically significant (p = .035). CONCLUSION: Hyperhidrosis, obesity, positive family history, tight clothing and chronic diseases may be considered important factors in acquiring dermatophytic infection. However, when it comes to difficult to treat tinea infections, irrational usage of topical steroids, treatment from non-dermatologists and a past history of tinea appear to be more critical causative factors. Treatment of dermatophytosis by dermatologists/ trained physicians and increasing general awareness of the public regarding the current situation about tinea in the country would help to alleviate the current crisis.

Dermatological diseases presented before COVID-19: Are patients with psoriasis and superficial fungal infections more vulnerable to the COVID-19?

Recent studies have focused on the comorbid conditions of the COVID-19. According to the current studies, numerous diseases including lung disease, cardiovascular disease and immunosuppression appear to be at higher risk for severe forms of the COVID-19. To date, there are no data in the literature on the comorbid dermatologic diseases and COVID-19. We tried to analyze the previous dermatological comorbidity of 93 patients with COVID-19 (51 males, 42 females) who presented to the dermatology outpatient clinics for the last 3 years. The most common dermatologic diseases in patients with COVID-19 who have dermatologic diseases for the last 3 years were superficial fungal infections (24, 25.8%), seborrheic dermatitis (11, 11.8%), actinic keratosis (10, 10.8%), psoriasis (6, 6.5%), and eczema (6, 6.5%), respectively. In addition, the number of COVID-19 patients who presented to dermatology in the last 3 months was 17 (11 men, 6 women). The median age of these patients was 58 (minimum 18, maximum 80) years, and the most common dermatologic diseases before diagnosed COVID-19 were superficial fungal infections (5, 25%), psoriasis (4, 20%), and viral skin diseases (3, 15%). The possible similarity between cutaneous and mucosal immunity and immunosuppression suggests that patients with some dermatologic diseases especially superficial fungal infections and psoriasis may be more vulnerable to the COVID-19.

Superficial fungal infections in the department of dermatology, University Hospital Jena: A 7-year retrospective study on 4556 samples from 2007 to 2013.

BACKGROUND: Superficial fungal infections are often seen in day-to-day clinical practice, and their prevalence continues to rise worldwide. Over the years, a change in the pattern of dermatophytoses has been noted. OBJECTIVES: This study aimed to determine the epidemiologic profile of dermatophytes at the Department of Dermatology, University Hospital Jena, from 2007 to 2013. METHODS: The retrospective study was carried out with a total of 4556 samples collected from 3607 patients suspected of superficial fungal infections during the 7-year study period. RESULTS: Among the 3607 suspected patients, 1951 (54.09%) were men and 1656 (45.91%) were women. Of 4556 samples, 703 (15.43%) samples were positive for fungal culture, which included 585 (83.21%) dermatophytes and 118 (16.79%) non-dermatophytes. Trichophyton (T.) rubrum was the most common isolated pathogen in 73.33% of the dermatophyte cases. Among dermatophyte-infected patients, men were most likely to be affected (63.48%) as well as those of higher age (61 to 80). The most commonly affected areas were nails (33.16%) and feet (33%). T rubrum was recurrently isolated in several regions with exception of the scalp where M canis (58.33%) was the most frequently isolated pathogen. About 16.04% of cases had a history of treatment taken prior to sampling. The majority of the affected individuals did not have any prior animal contact (77.26%). T benhamiae was exclusively associated with contact to guinea pigs. CONCLUSION: Trichophyton rubrum was the most frequently isolated pathogen in several regions except the scalp. New dermatophyte species emerged with time especially T benhamiae.

Species distribution and epidemiological characteristics of superficial fungal infections in Southeastern Serbia.

BACKGROUND: Superficial fungal infections (SFI), one of the most prevalent diseases in the world, are infections of keratin-rich structures of human body mostly caused by dermatophytes and yeasts. OBJECTIVES: The goal of this study was to determine the possible changes in the epidemiology of SFI on the territory of Southeastern Serbia and to investigate epidemiological characteristics and the influence of SFI on the patient's quality of life. METHODS: From 2012 to the end of 2017, samples of 1643 patients (568 males and 1075 females, mean age 40.32 ± 22.44 years) with suspected SFI from Southeastern Serbia were examined using the standard mycological methods. The questionnaires were used to investigate epidemiological characteristics. RESULTS: Superficial fungal infections were diagnosed in 20.5% (n = 336) of patients. In the group of dermatophytes, the most prevalent was Microsporum canis (63.9%, n = 76) followed by Trichophyton mentagrophytes (21.8%, n = 26). Non-albicans Candida species were dominant aetiological agents of superficial candidosis (62.3%). BMI ≥25 kg/m2 (P = 0.019) was determined as an independent risk factor for SFI. There was a statistically significant difference in the EQVAS score between the groups of patients and the control group (P < 0.001). CONCLUSIONS: Results of conducted study indicate that SFI prevalence has not changed in the previous period. However, increase of Candida-SFI prevalence, especially Candida onychomycosis, was established.

Epidemiology of Superficial Fungal Infections in Guangdong, Southern China: A Retrospective Study from 2004 to 2014.

Superficial fungal infections are common worldwide; however, the distribution of pathogenic species varies among geographical areas and changes over time. This study aimed to determine the epidemiologic profile of superficial fungal infections during 2004-2014 in Guangzhou, Southern China. Data regarding the superficial mycoses from outpatients and inpatients in our hospital were recorded and analyzed. From the 3367 patients that were enrolled in the study, 3385 samples were collected from skin, hair and nail lesions. Of the 697 positive cultures, dermatophytes were the most prevalent isolates (84.36 %), followed by yeasts (14.92 %) and non-dermatophyte molds (0.72 %). Trichophyton rubrum (56.24 %) was the most common dermatophyte isolated from cases of tinea unguium (83.92 %), tinea pedis (71.19 %), tinea cruris (91.66 %), tinea corporis (91.81 %) and tinea manuum (65.00 %). Trichophyton mentagrophytes (13.35 %) and Microsporum canis (10.19 %) were the predominant species associated with cases of tinea faciei (54.55 %) and tinea capitis (54.13 %), respectively. Yeasts and molds were identified primarily from other cases of superficial fungal infections. In conclusion, when compared to previous studies in the same area, the epidemiology of superficial mycoses in Guangdong did not significantly change from 2004 to 2014. The prevalence of causative agents and the spectrum of superficial fungal infections, particularly tinea caused by dermatophyte infection, are similar to reports from several specific regions in China and Europe, whereas increasing incidences of Trichophyton mentagrophytes and Microsporum canis occurred in Guangdong, China.

Safety and efficacy of new generation azole antifungals in the management of recalcitrant superficial fungal infections and onychomycosis.

INTRODUCTION: Terbinafine is considered the gold standard for treating skin fungal infections and onychomycosis. However, recent reports suggest that dermatophytes are developing resistance to terbinafine and the other traditional antifungal agents, itraconazole and fluconazole. When there is resistance to terbinafine, itraconazole or fluconazole, or when these agents cannot used, for example, due to potential drug interactions with the patient's current medications, clinicians may need to consider off-label use of new generation azoles, such as voriconazole, posaconazole, fosravuconazole, or oteseconazole. It is essential to emphasize that we do not advocate the use of newer generation azoles unless traditional agents such as terbinafine, itraconazole, or fluconazole have been thoroughly evaluated as first-line therapies. AREAS COVERED: This article reviews the clinical evidence, safety, dosage regimens, pharmacokinetics, and management algorithm of new-generation azole antifungals. EXPERT OPINION: Antifungal stewardship should be the top priority when prescribing new-generation azoles. First-line antifungal therapy is terbinafine and itraconazole. Fluconazole is a consideration but is generally less effective and its use may be off-label in many countries. For difficult-to-treat skin fungal infections and onychomycosis, that have failed terbinafine, itraconazole and fluconazole, we propose consideration of off-label voriconazole or posaconazole.

An update on antifungal resistance in dermatophytosis.

INTRODUCTION: The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention. AREAS COVERED: This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent). EXPERT OPINION: Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.

Clinico-Demographic Parameters of Oral Fungal Infections: An Institutional Retrospective Study.

Introduction Most fungal infections are responsive to antifungal therapy. However, failure to diagnose the same can significantly affect the quality of lives of patients. Timely identification of fungal infections and their association with varied demographic and clinical parameters will help in improving the prognosis of the patient. The present study aims to evaluate the prevalence of fungal infections among various age groups and genders and also to evaluate the association of fungal infections with demographic parameters. Methods This study included a sample size of n = 600. The demographic and clinical details were compiled and transferred to IBM SPSS Version 23 software (IBM Corp., Armonk, NY) for statistical analysis. Descriptive and Pearson chi-square tests were used to analyze the association of the type of fungal infection with gender, age, and comorbidities. A p-value of less than 0.05 is considered statistically significant. Results Angular cheilitis (40%, 240), followed by denture stomatitis (37.5%, 225), were the most common type of fungal infection among the sample population, and the elderly age group (51-72 years) was the most affected. Angular cheilitis was the most common infection among both males (21.4%, 128) and females (18.6%, 112), but candidiasis was reported more in females (18%, 108) than males (3%, 18) (p = 0.00). Angular cheilitis (32%, 192) and candidiasis (18%, 108) were more observed in association with anemia; however, denture stomatitis (34%, 204) was significantly higher among diabetics (p = 0.00). Conclusion The identification of associated systemic and demographic factors is as important as the treatment of fungal infection itself. The recognition of fungal infections and the role of parameters like age, gender, and systemic comorbidities in the development of fungal infections will have valuable implications for public health. Future research is required for a clear understanding of the same.

Apolipoprotein E Gene Polymorphism, Serum Lipids, and Risk of Superficial Fungal Infections in Egyptian Patients - A Preliminary Case-Controlled Study.

Background: Apolipoprotein E (APOE) gene isoforms have been found to affect the risk of superficial fungal infections (SFIs). However, the data only cover a few ethnicities. Aims: The present work intended to investigate the association of APOE gene polymorphism and serum lipids with the susceptibility of SFIs among a group of Egyptian patients. Materials and Methods: Standard laboratory methods were used to estimate the serum lipid profile, and polymerase chain reaction-restriction fragment length polymorphism was used to detect APOE gene polymorphism in deoxyribonucleic acid extracted from 150 SFI patients and an equal number of apparently healthy matched controls. Results: Serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol were significantly higher in the studied patients than in controls. The APOE gene ε2, ε4 alleles, and ε3/4 and ε3/2 genotypes were significantly distributed in the patients than in the controls. APOE ε3/3 genotype was predominant in dermatophytosis and tinea versicolour patients, and ε3/4 genotype was predominant in candidiasis. Conclusions: ApoE alleles ε2 and ε4, and genotypes ε2/3 and ε3/4 are linked to SFI and may be risk factors, whereas allele ε3 and genotype ε3/3 may be protective for SFI in the Egyptian population studied. The lipid profile results suggest that hyperlipidemia may provide evidence for SFI pathogenesis. However; further large-scale studies are still needed to validate our results.

The Optimal Dosing Regimen of Super Bioavailable Itraconazole in Obesity: An Experimental Rat Model Study.

Background Obesity may alter tissue distribution and clearance of several drugs, especially lipophilic ones. Itraconazole, a lipophilic drug, has been recently introduced in a super-bioavailable formulation (SB-ITZ) for the treatment of dermatophytosis. Evidence regarding optimal dosing of SB-ITZ in obesity is lacking. A current experimental study was planned to analyze tissue concentrations of SB-ITZ at different doses in obese and non-obese rats.  Materials and methods Thirty-six Wistar albino rats of either sex were divided into obese and non-obese rats equally. Further, rats in both categories were divided into three dosing groups. Group 1 received SB-ITZ 13 mg once daily in the morning, group 2 received SB-ITZ 13 mg in the morning and 6.5 mg in the evening, while Group 3 rats received SB-ITZ 13 mg twice daily, orally. Concentrations of SB-ITZ in the skin, serum, and fatty tissue were assessed in each group on days 7, 14, 21, and 28. Comparison of SB-ITZ concentrations in various tissues in obese and non-obese rats and inter-group comparison of tissue concentrations across the three dosing regimens was done at day 28 and expressed as Mean ± SD.36 Wistar rats were divided into obese and non-obese rats equally. Results At day 28, skin concentrations of SB-ITZ were 5.36±1.1, 8.9±1.7 and 10.13±1.7 µg/g in Groups 1, 2, and 3, respectively, in non-obese rats, which was statistically significant (p<0.05) than skin concentration of obese rats (2.72±0.6, 4.2±0.7 and 4.66±0.5 µg/g) for the corresponding dosing groups respectively. Skin concentration of SB-ITZ was statistically significant for Groups 2 and 3 as compared to Group 1. Still, no statistically significant difference was noted between Groups 2 and 3 in non-obese and obese rats. Fatty tissue concentration of SB-ITZ was comparable in all 3 dosing regimens in non-obese and obese rats. But on the intergroup comparison, a statistically significant difference was observed for Groups 2 and 3 against Group 1 (p<0.05). Increasing the dose of SB-ITZ increased serum concentration. In non-obese rats, a statistically significant difference was noted between Group 2 (74.33±6.6 ng/ml) and Group 1 (52.5±9.9 ng/ml); p<0.01 and also in Group 3 (81.33±6.8 ng/ml) against Group 1; p<0.01. Group 3 achieved significantly higher concentration than the other two groups in obese rats (Group 3; 72±5.3, Group 2; 60.5±4.3, and Group 1; 45±7 ng/ml; p<0.01). Conclusion Overall, skin, fatty tissue, and serum concentrations of SB-ITZ were higher in non-obese rats compared to obese rats in all three dosing groups. Moreover, skin and fatty tissue concentrations were proportionately higher than serum in all the groups in non-obese and obese rats. Though the skin concentration of non-obese rats was significantly higher than obese rats, skin concentration in obese rats was within the minimum inhibitory concentration (MIC) range, demonstrating the efficacy of all dosing regimens.

Developing a new treatment for superficial fungal infection using antifungal Collagen-HSAF dressing.

Fungal pathogens are common causes of superficial clinical infection. Their increasing drug resistance gradually makes existing antifungal drugs ineffective. Heat stable antifungal factor (HSAF) is a novel antifungal natural product with a unique structure. However, the application of HSAF has been hampered by very low yield in the current microbial producers and from extremely poor solubility in water and common solvents. In this study, we developed an effective mode of treatment applying HSAF to superficial fungal infections. The marine-derived Lysobacter enzymogenes YC36 contains the HSAF biosynthetic gene cluster, which we activated by the interspecific signaling molecule indole. An efficient extraction strategy was used to significantly improve the purity to 95.3%. Scanning electron microscopy images revealed that the Type I collagen-based HSAF (Col-HSAF) has a transparent appearance and good physical properties, and the in vitro sustained-release effect of HSAF was maintained for more than 2 weeks. The effective therapeutic concentration of Col-HSAF against superficial fungal infection was explored, and Col-HSAF showed good biocompatibility, lower clinical scores, mild histological changes, and antifungal capabilities in animals with Aspergillus fumigatus keratitis and cutaneous candidiasis. In conclusion, Col-HSAF is an antifungal reagent with significant clinical value in the treatment of superficial fungal infections.

Towards Better CARE for Superficial Fungal Infections: A Consultation Guide for the Community Pharmacy.

Superficial fungal infections (SFIs) are among the most common skin diseases worldwide and are common in many parts of Asia. Community pharmacists are well-placed to help identify and manage SFIs. However, effective management may be hindered by a suboptimal consultation process, attributed to the misalignment between consumers' and pharmacists' viewpoints. The Fungal CARE (Care, Assess, Recommend, Empower) guide, a patient-centered collaborative framework, was developed to improve pharmacist-led SFI consultations in community pharmacy. A survey on real-world consumer experiences with SFIs provided insights for aligning the Fungal CARE guide with consumer perspectives. To further optimize the guide, community pharmacists were surveyed on their current practice and challenges of managing SFIs, as well as views on the usefulness of the Fungal CARE guide. The pharmacists' survey indicated that respondents engaged with some but not all of consumers' top concerns with SFIs, such as emotional and social aspects. Pharmacists identified their greatest challenges as poor compliance with SFI treatment and limited confidence in identifying and/or managing SFIs. Encouragingly, when presented with the Fungal CARE guide, nearly all pharmacists agreed it would be helpful and would use it in practice. Implementing the Fungal CARE guide may help improve pharmacist-led consultations for SFIs and encourage better treatment outcomes.

Risk factors associated with acquiring superficial fungal infections in school children in South Western Nigeria: a comparative study.

INTRODUCTION: Superficial fungal infections (SFI) are caused mainly by dermatophytes and yeasts. SFI is of major public health concern and is a common cause of skin disease among school children. OBJECTIVES: The aim of this study was to identify the risk factors associated with acquiring superficial fungal infections in school children in Ile-Ife, South West Nigeria as this will assist in instituting appropriate interventions. METHODS: A total of 560 children; 280 with superficial fungal infections as subjects and 280 age and sex matched school children as controls were recruited through multistage sampling method from 10 primary schools (private and public owned) in Ile-Ife, Nigeria. DISCUSSION: Pupils were aged 5-16 years with a mean age of 9.42±2.00. Risk factors documented in this study included poor living conditions, use of barbers' clippers, low socio-economic status, poor hygiene, attendance of public schools and not living with both parents. The last four factors remained significant on binary logistic regression. CONCLUSION: The study shows that the risk for acquiring superficial fungal infections remains high in school children and in communities with low socio-economic positions.

Terbinafine-loaded wound dressing for chronic superficial fungal infections.

In spite of developing new drugs and modern formulations, the treatments of chronic fungal infections are still challenging. Fibrous wound dressings are new suggestions for the treatment of chronic superficial infections. In the present study, we formulated an antifungal agent, terbinafine hydrochloride (TFH), which is a hydrophobic drug, in wound dressings prepared by electrospun polycaprolactone, polycaprolactone/gelatin (50:50 w/w) and gelatin. To obtain more water-stable meshes, the preparations were treated by glutaraldehyde and their properties were determined before and after treatment. The morphology of fibrous meshes was observed by scanning electron microscopy. Drug loading efficiency and release rate were measured by high performance liquid chromatography (HPLC) and the release rate was monitored for 144h. Antifungal tests were performed on Trichophyton mentagrophytes, Aspergillus fumigatus and Candida albicans cultured on Muller-Hinton agar. The toxicity of the meshes was measured after 24h and 14days by MTT assay. Terbinafine loading of polycaprolactone/gelatin (50:50) was 100% and it released the highest amount of TFH too. In antifungal tests, all samples were able to hinderT. mentagrophytes and A. fumigatus but not C. albicans growth among them, polycaprolactone fibers made the largest inhibition zone. In MTT assay, none of prepared samples showed toxicity against L929 cells. Teken together, the prepared TFH-loaded PCL/gelatin electrospun meshes were able to release TFH slowly and in a steady state in time. With respect to no obvious cytotoxicity in MTT assay and stong antifungal activity toward T. mentagrophytesin vitro, these TFH-based meshes could be considered as potential candidates in clinical application as wound dressing for treatment of chronic dermatophytosis.

Efficacy and safety of itraconazole use in infants.

BACKGROUND: Itraconazole has been used to treat fungal infections, in particular invasive fungal infections in infants or neonates in many countries. DATA SOURCES: Literature search was conducted through Ovid EMBASE, PubMed, ISI Web of Science, CNKI and Google scholarship using the following key words: "pediatric" or "infant" or "neonate" and "fungal infection" in combination with "itraconazole". Based on the literature and our clinical experience, we outline the administration of itraconazole in infants in order to develop evidence-based pharmacotherapy. RESULTS: Of 45 articles on the use of itraconazole in infancy, 13 are related to superficial fungal infections including tinea capitis, sporotrichosis, mucosal fungal infections and opportunistic infections. The other 32 articles are related to systemic fungal infections including candidiasis, aspergillosis, histoplasmosis, zygomycosis, trichosporonosis and opportunistic infections as caused by Myceliophthora thermophila. CONCLUSION: Itraconazole is safe and effective at a dose of 5 mg/kg per day in a short duration of therapy for superficial fungal infections and 10 mg/kg per day for systemic fungal infections in infants. With a good compliance, it is cost-effective in treating infantile fungal infections. The profiles of adverse events induced by itraconazole in infants are similar to those in adults and children.

Management of tinea corporis, tinea cruris, and tinea pedis: A comprehensive review.

The prevalence of superficial mycotic infection worldwide is 20-25% of which dermatophytes are the most common agents. Recent developments in understanding the pathophysiology of dermatophytosis have confirmed the central role of cell-mediated immunity in countering these infections. Hence, a lack of delayed hypersensitivity reaction in presence of a positive immediate hypersensitivity (IH) response to trichophytin antigen points toward the chronicity of disease. Diagnosis, though essentially clinical should be confirmed by laboratory-based investigations. Several new techniques such as polymerase chain reaction (PCR) and mass spectroscopy can help to identify the different dermatophyte strains. Management involves the use of topical antifungals in limited disease, and oral therapy is usually reserved for more extensive cases. The last few years have seen a significant rise in the incidence of chronic dermatophyte infections of skin which have proven difficult to treat. However, due to the lack of updated national or international guidelines on the management of tinea corporis, cruris, and pedis, treatment with systemic antifungals is often empirical. The present review aims to revisit this important topic and will detail the recent advances in the pathophysiology and management of tinea corporis, tinea cruris, and tinea pedia while highlighting the lack of clarity of certain management issues.

Ethosomes for enhanced skin delivery of griseofulvin.

Griseofulvin (GRF) is an important antifungal drug with low bioavailability and, for this reason, a topical formulation with a targeted action and minimal systemic effects, appears to be a preferable solution. GRF poor solubility has limited the development of topical formulations and their release to the market. The aim of this work was to prepare a new GRF formulation for topical application using lipid-based nanosystems; to study its permeation and penetration, cell viability and to evaluate its therapeutic action. Ethosomal systems composed of soy bean phosphatidylcholine, ethanol and water were prepared for incorporating GRF. After the characterization of the vesicles in terms of size, charge and penetrability, permeation through newborn pig using Franz diffusion cells was conducted. Cell viability at different concentrations of the chosen formulation was determined. At last, skin adapted agar diffusion test was performed to assess the therapeutic efficacy of the formulation. GRF vesicles had mean size of 130nm. Permeation and penetration assays revealed that GRF-loaded ethosomes have an adequate profile to be used in a topical formulation since drug retention in the stratum corneum was achieved. Cell viability tests proved this formulation presented no cytotoxicity to HaCaT cells for concentrations below 50µg/mL. The skin diffusion test evidenced the potential of developed formulation to target skin dermatophytes. The results obtained in this study contribute to a new perspective in topical treatment of fungal infections.

Antifungal activity of 40 TCMs used individually and in combination for treatment of superficial fungal infections.

ETHNOPHARMACOLOGICAL RELEVANCE: A series of 40 important Traditional Chinese Medicines (TCMs), which were reported effective in treating superficial fungal infections of the skin in Chinese clinical trial publications and Chinese Herbal Classics, were chosen for the investigation of the individual and combination antifungal properties against 8 superficial fungal strains in vitro. MATERIALS AND METHODS: Plant preparations were followed the theory of TCM by using sterile water boiled with plant material at 100°C to produce water decoction of the tested sample. The minimum inhibitory concentration (MIC) of each plant for each fungus was determined. For the compatibility investigation, both invariable (same amounts of each tested TCM) and variable (different amounts of each tested TCM) combinations were evaluated. RESULTS: All the tested TCMs demonstrated varying degrees of antifungal activities against one or more of the tested superficial fungi, and 16 of which were effective on all of the fungi. Strong antifungal activities were exhibited by water decoction of 7 TCMs with MIC at about 100µg/ml, and among these effective antifungal extracts, 4 TCMs including Melaphis chinensis, Polygonum cuspidatum, Punica granatum and Schisandra chinensis showed the significantly inhibitory activities against all of the fungi with MICs among 50µg/ml. Most of the invariable combinations of the above-mentioned 4 TCMs showed synergic effects against 4 of the least susceptible fungi strains, especially the invariable combination of Punica granatum, Melaphis chinensis and Schisandra chinensis, with the MIC at 23.4µg/ml. However, their further variable combinations investigation demonstrated that only the combination of 7.5g Punica granatum with 10g Melaphis chinensis and 7.5g Schisandra chinensis showed synergic effect with the MIC at19.5µg/ml. CONCLUSIONS: The present study aimed the discovery of therapeutically useful agents for treatment of superficial fungal infections. Findings suggested that the combination of 3 TCMs including Punica granatum, Melaphis chinensis and Schisandra chinensis showed potential antifungal activity and thus appeared to be promising agents in preventing superficial fungal skin infectious in a natural way through herbal resources. The synergic effects of invariable and variable combinations of the tested TCMs threw a light on our further animal model and clinical practice as well as the bio-guided isolation and identification of the antifungal compounds.

[Epidemiological and etiological aspects of superficial fungal infections among prison inmates in Ouagadougou, Burkina Faso]. / Aspects épidémiologiques et étiologiques des mycoses cutanéo-phanériennes chez les détenus de la maison d'arrêt et de correction de Ouagadougou (Burkina Faso).

OBJECTIVE: The fight against fungal infections in prisons is within the overall framework of the fight against these diseases in the general population. To contribute to the fight against these diseases, we conducted this study among inmates of the big prison of Ouagadougou. It aimed to analyze the epidemiological and etiological aspects of superficial fungal infections among prison inmates in Ouagadougou. MATERIALS AND METHODS: It was a matter of an analytical descriptive study (December 2011-April 2012) that examined 212 selected using a stratified sampling detainees. It consisted firstly of a survey on risk factors. Secondly, samples were taken from prisoners with suspicious lesions of superficial mycoses. For each lesion, some fragments were examined directly between slide and coverslip in KOH (10% or 30%). The remaining fragments were cultured on Sabouraud-Chloramphenicol and Sabouraud-Chloramphenicol-Actidione. The media were then incubated at 27°C for 1 month before declaring any negativity. RESULTS: The overall prevalence of superficial fungal infections among prison inmates Ouagadougou was 25.5%. The recent prison inmates (≤24 months) were the most affected (89.8%). Dermatophytes (15.56%) were more isolated than non-dermatophytes (12.26%) Anthropophilic species predominated among dermatophytes: T. mentagrophytes (7.0%), T. rubrum (3.3%), M. langeronii (23%), E. floccosum (1.41%) and T. violaceum (0.94%). M. gypseum (0.47%) was the only land-based species encountered. Non-dermatophytes were Malassezia sp. (11.79%) and Candida sp. (0.47%). Polyparasitism was less represented (7.4% of infected prisoners). Several body sites were mostly infected by one fungal agent. Pityriasis versicolor was the most common fungal infection (37.31%). CONCLUSION: Considering the results, specific control measures are to be taken against the superficial fungal infections in prisons and in the general population.