Global perspectives for the management of onychomycosis.

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophyte molds, and yeasts. This difficult-to-treat chronic infection has a tendency to relapse despite treatment. This paper aims to offer a global perspective on onychomycosis management from expert physicians from around the world. Overall, the majority of experts surveyed used systemic, topical, and combination treatments approved in their countries and monitored patients based on the product insert or government recommendations. Although the basics of treating onychomycosis were similar between countries, slight differences in onychomycosis management between countries were found. These differences were mainly due to different approaches to adjunctive therapy, rating the severity of disease and use of prophylaxis treatment. A global perspective on the treatment of onychomycosis provides a framework of success for the committed clinician with appreciation of how onychomycosis is managed worldwide.

Blad-containing oligomer: a novel fungicide used in crop protection as an alternative treatment for tinea pedis and tinea versicolor.

PURPOSE: The lack of novel antifungal drugs and the increasing incidence and severity of fungal infections are major concerns worldwide. Herein, we tested the activity of the Blad-containing oligomer (BCO), a new antifungal molecule already in use for agriculture, on Malassezia spp. and dermatophytes, the causal agents of human tinea versicolor and tinea pedis. Given the lack of a standard method for Malassezia susceptibility testing and the plethora of published methods, we also developed an improved method for this genus. METHODOLOGY: The efficacy of BCO was assessed in vitro and compared to that of the drugs currently utilized in the treatment of tinea versicolor (fluconazole and itraconazole) and tinea pedis (itraconazole and terbinafine). For dermatophytes, the standard microdilution broth-based method was used, with small adjustments, and several broth formulations and inocula sizes were tested to develop an improved susceptibility method for Malassezia spp. RESULTS: We successfully developed a microdilution broth-based method with considerable advantages over other available methods, and used it for all in vitro susceptibility tests of Malassezia spp. isolates. We report that, on a molar basis, BCO was more effective than fluconazole or itraconazole on most strains of Malassezia spp. isolated from clinical samples (n=29). By contrast, BCO was less effective than itraconazole or terbinafine on the common dermatophytes Trichophyton rubrum and Trichophyton interdigitale. CONCLUSION: These data place BCO as a promising drug for the treatment of Malassezia-associated skin diseases. Further in vivo studies are now required to ascertain its applicability in the clinical setting.

Oxyresveratrol, a Stilbene Compound from Morus alba L. Twig Extract Active Against Trichophyton rubrum.

Morus alba L. (mulberry) twig is known to have an inhibitory effect on pathogens in traditional Chinese medicine. In the present study, the dermophytic fungus, Trichophyton rubrum, was used to evaluate the inhibitory effect of total M. alba twig extract and extracts obtained using solvents with different polarities by the method of 96-well MTT colorimetry. The main active substance was isolated and identified by tracking its activity. In addition, the inhibitory effects of active extracts and a single active substance were investigated in combination with miconazole nitrate. Our data indicated that ethyl acetate extracts of mulberry twig (TEE) exhibited a desired inhibitory activity on T. rubrum with the minimum inhibitory concentration (MIC) of 1.000 mg/mL. With activity tracking, the main substance showing antimicrobial activity was oxyresveratrol (OXY), which was isolated from TEE. Its MIC for inhibiting the growth of T. rubrum was 0.500 mg/mL. The combined use of miconazole nitrate and OXY showed a synergistic inhibitory effect, as shown by a significant decrease in the MIC of both components. Based on the OXY content in TEE, the contribution rate of OXY to the inhibitory effect of TEE on T. rubrum was 80.52%, so it was determined to be the main antimicrobial substance in M. alba twig. Copyright © 2017 John Wiley & Sons, Ltd.

Discovery of antifungal constituents from the Miao medicinal plant Isodon flavidus.

ETHNOPHARMACOLOGICAL RELEVANCE: Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara. AIM OF THE STUDY: The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant. MATERIALS AND METHODS: The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A (1) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum. They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans, Porphyromonas gingivalis and Candida albicans. RESULTS: Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A (1) and lophanic acid (2). Fladin A (1) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid (2) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8µg/mL, and fladin A (1) also showed inhibition activity against the fungus with a MIC value of 62.5µg/mL. CONCLUSIONS: Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study.

Once-daily luliconazole cream 1% for the treatment of interdigital tinea pedis.

Luliconazole is an imidazole antifungal agent with a unique chemical structure. In this article, we summarize the in vitro data, animal studies and clinical trial data relating to the use of topical luliconazole cream 1% in the treatment of tinea pedis. Preclinical studies have demonstrated potent activity against dermatophytes. Luliconazole has strong fungicidal activity against Trichophyton spp., similar to that seen with terbinafine. Evidence from clinical trials in tinea pedis have shown once-daily application of luliconazole cream 1% for 14 days to be effective and well tolerated.

Anti-dermatophytic activity of bakuchiol: in vitro mechanistic studies and in vivo tinea pedis-inhibiting activity in a guinea pig model.

Bakuchiol was an active antifungal compound isolated from Psoraleae Fructus by means of bioassay-guided fractionation in our previous study. The present work aimed to investigate the underlying mechanisms and the therapeutic effect of bakuchiol in Trichophyton mentagrophytes-induced tinea pedis. After exposure to bakuchiol at 0.25-fold, 0.5-fold and 1-fold of minimum inhibitory concentration (MIC) (3.91 µg/ml) for 24h, the fungal conidia of T. mentagrophytes demonstrated a significant dose-dependent increase in membrane permeability. Moreover, bakuchiol at 1-fold MIC elicited a 187% elevation in reactive oxygen species (ROS) level in fungal cells after a 3-h incubation. However, bakuchiol did not induce DNA fragmentation. In a guinea pig model of tinea pedis, bakuchiol at 1%, 5% or 10% (w/w) concentration in aqueous cream could significantly reduce the fungal burden of infected feet (p<0.01-0.05). In conclusion, this is the first report to demonstrate that bakuchiol is effective in relieving tinea pedis and in inhibiting the growth of the dermatophyte T. mentagrophytes by increasing fungal membrane permeability and ROS generation, but not via induction of DNA fragmentation.

Sanitization of contaminated footwear from onychomycosis patients using ozone gas: a novel adjunct therapy for treating onychomycosis and tinea pedis?

BACKGROUND: Ozone gas possesses antimicrobial properties against bacteria, viruses, and yeasts. Previously, we demonstrated the efficacy of ozone in killing ATCC strains of the dermatophyte fungi Trichophyton rubrum and Trichophyton mentagrophytes. OBJECTIVE: To test the efficacy of ozone gas in sanitizing onychomycosis patient footwear contaminated with fungal material as a means of minimizing the risk of reinfection. METHODS: Swabs of footwear from onychomycosis patients were cultured prior to and after ozone exposure to test the ability of ozone to sanitize these items. RESULTS: We identified contamination of footwear from most onychomycosis patients, a potential source of reinfection in these individuals. Furthermore, ozone gas was effective in sanitizing contaminated footwear. CONCLUSION: Ozone gas is effective in sanitizing footwear and represents a novel adjunct therapy to be used in conjunction with antifungal medications and/or devices to better treat onychomycosis and tinea pedis patients in both the short and the long term.

Topical treatment of tinea pedis using 6% coriander oil in unguentum leniens: a randomized, controlled, comparative pilot study.

BACKGROUND: The antifungal activity of coriander oil has already been demonstrated in vitro. OBJECTIVE: Evaluation of the efficacy and tolerability of 6% coriander oil in unguentum leniens in the treatment of interdigital tinea pedis. METHODS: Half-side comparative pilot study on subjects with symmetric, bilateral interdigital tinea pedis. Active drug and placebo control were applied twice daily on the affected areas, and follow-up visits were performed on days 14 and 28. RESULTS: 40 participants (mean age 52.5 years, 60% male) were included in the study. For 6% coriander oil in unguentum leniens, a highly significant improvement of the clinical signs (p < 0.0001) was observed during the entire observation period; the number of positive fungal cultures also tended to decrease (p = 0.0654). The tolerability of the tested substances was good. CONCLUSION: Coriander oil is effective and well tolerated in the treatment of interdigital tinea pedis.

Effects of a foot bath containing green tea polyphenols on interdigital tinea pedis.

BACKGROUND: It has been shown that green tea polyphenols (GTP) can directly kill Trichophyton in vitro; however, there are no published clinical studies that show anti-fungal activity of GTP. OBJECTIVES: To identify the effects of GTP on interdigital tinea pedis in elderly patients. METHOD: Ninety-four patients with interdigital tinea pedis were enrolled and were either given a lukewarm water foot bath containing GTP or placebo treatment. Effects of GTP were assessed based on changes in the size of the affected area, the rate of recurrence, microscopy findings, and overall assessment of skin changes. RESULTS: After 12 weeks of treatment with either GTP or placebo, a significant reduction in the size of the affected area was observed (p<0.001). There were no significant differences between the GTP or placebo groups in the size of the affected area (p=0.638), the recurrence rate (p=0.172), or the microscopy findings (p=1.000). However, the overall assessment demonstrated significant improvements (p=0.010) in the GTP group. CONCLUSIONS: These results show that GTP was effective in improving the symptoms of tinea pedis in comparison to only lukewarm water. Our results suggest that GTP could have anti-fungal activity.

Therapeutic effectiveness of Ageratina pichinchensis on the treatment of chronic interdigital tinea pedis: a randomized, double-blind clinical trial.

OBJECTIVES: Interdigital tinea pedis is the most frequent presentation, as well as the most severe clinical form of tinea pedis, constituting a therapeutic challenge. The aim of the study was to evaluate the effectiveness and tolerability of two concentrations of Ageratina pichinchensis extract (encecalin content, 0.76 and 1.52%, respectively) on patients with clinical and mycological diagnosis of chronic interdigital tinea pedis. DESIGN: By means of a randomized, double-blind clinical trial, three groups of patients were treated topically for 4 weeks with a cream containing the following: Group I-the lower concentration of A. pichinchensis extract, group II-the higher concentration, group III-2% ketoconazole. SUBJECTS: One hundred and sixty (160) ambulatory patients of either sex between the ages of 18 and 65 years were enrolled. OUTCOME MEASURES: The primary outcome variables were: clinical effectiveness, mycological effectiveness, therapeutic cure, tolerability, and treatment compliance. The secondary outcome variable was therapeutic success. RESULTS: At the end of treatment, therapeutic cure was achieved by 34.1, 41.8, and 39.53% of Groups I, II, and III, respectively. No statistical difference between the groups was observed. CONCLUSIONS: Both treatments were effective for the treatment of interdigital-type tinea pedis, while better results were observed on patients that received the higher concentration of the extract.

In vitro antifungal susceptibility of dermatophyte strains causing tinea pedis and onychomycosis in patients with non-insulin-dependent diabetes mellitus: a case-control study.

BACKGROUND: The efficacy of antifungal treatment may be reduced and/or delayed in diabetic patients. To date, no study has investigated the in vitro antifungal susceptibility of dermatophytes in this patient group. OBJECTIVE: We aimed to determine the dermatophyte species causing tinea pedis and onychomycosis, and in vitro susceptibility of these dermatophytes to terbinafine, itraconazole, and fluconazole in patients with non-insulin-dependent diabetes mellitus. We compared the findings in diabetic patients with those in non-diabetic individuals. MATERIALS AND METHODS: One hundred patients with non-insulin-dependent diabetes mellitus and 100 otherwise healthy controls clinically suspected with tinea pedis and/or onychomycosis were included. Skin scrapings and/or nail clippings were taken and cultured on Sabouraud dextrose agar, mycobiotic agar, and dermatophyte test medium. In vitro antifungal susceptibility tests were carried out according to the Clinical and Laboratory Standards Institute (CLSI) M-38P protocol with some modifications. RESULTS: Fifty-seven samples of 54 diabetics and 50 samples of 50 controls grew dermatophytes. In both groups, Trichophyton rubrum was the most common isolate. Mean MIC values of terbinafine, itraconazole, and fluconazole for all of the isolated dermatophyte strains were similar in two groups (P>0.05). The difference in mean MIC values of three antifungals for T. rubrum and T. mentagrophytes between two groups was not statistically significant (P>0.05). CONCLUSIONS: Dermatophyte types causing tinea pedis and onychomycosis, their frequency patterns, and in vitro activity of three antifungals against dermatophytes in diabetics are similar to the non-diabetics. Terbinafine is the most active agent in vitro in both groups.

Active compounds against tinea pedis dermatophytes from Ageratina pichinchensis var. bustamenta.

Secondary metabolites 5-acetyl-3beta-angeloyloxy-2beta-(1-hydroxyisopropyl)-2,3-dihydrobenzofurane (1), 5-acetyl-3beta-angeloyloxy-2beta-(1-hydroxyisopropyl)-6-methoxy-2,3-dihydrobenzofurane (2), espeletone (3), encecalinol (4), O-methylencecalinol (5), encecalin (6), sonorol (7), taraxerol (8), (+)-beta-eudesmol (9), and a mixture of beta-sitosterol and stigmasterol, were isolated from the aerial parts of Ageratina pichinchensis var. bustamenta. The antimicrobial activity of compounds 6, 8 and 9, together with derivatives 9a and 9b against the most important dermatophytes responsible for tinea pedis infection, Trichophyton rubrum and T. mentagrophytes, and against Candida albicans and Aspergillus niger were determined, showing that the three natural products were active against both Trichophyton species. Ageratina pichinchensis var. bustamenta is used in folk medicine to treat skin infections and wounds, and this study confirms that the n-hexane extract contains metabolites which are responsible for these utilities.

Effectiveness and tolerability of a standardized extract from Ageratina pichinchensis on patients with tinea pedis: an explorative pilot study controlled with ketoconazole.

Ageratina pichinchensis has been used for many years in Mexican traditional medicine for the treatment of superficial mycosis. Previous studies have demonstrated the antifungal effectiveness of a hexane extract from aerial parts of this plant on in vitro cultures of Candida albicans, Aspergillium niger, Trichophyton mentagrophytes, and Trichophyton rubrum. To compare the effectiveness and tolerability of A. pichinchensis with ketoconazole in patients with the clinical and mycological diagnosis of tinea pedis, we carried out a double-blind pilot study. The experimental group was treated topically with a cream containing A. pichinchensis standardized extract (10 %), while the control group was administered a similarly colored cream containing 2 % ketoconazole. All patients were clinically followed weekly for 4 weeks. By means of a mycological examination (direct microscopic detection), the mycological diagnosis of tinea pedis was performed. This technique was also used for evaluating the mycological effectiveness at the end of treatment. A total of 120 patients were included, 60 in each treatment group. Of these, 97 patients were included in the statistical analysis, 51 from the experimental group and 46 controls. The remainder of the patients withdrew from the study due to non-medical causes. Clinical effectiveness was reached in 80.3 and 76 %, while therapeutic success was achieved in 80.3 and 71.7 % of the experimental and control groups, respectively. There were no statistical differences between groups (P = 0.31). Our results suggest the effectiveness and tolerability of a standardized extract from A. pichinchensis in treatment of patients with tinea pedis.

Autosensitization dermatitis associated with propolis-induced allergic contact dermatitis.

Propolis is a beehive product known for its anti-inflammatory properties. With its growing use, propolis-induced contact dermatitis is increasing. While the dermatitis mostly occurs on areas directly exposed to propolis, our case presented an additional eczema at a site distant from the primary propolis-induced contact dermatitis twice in the same individual. We diagnosed it as an autosensitization dermatitis associated with propolis-induced allergic contact dermatitis.

What defines the quality of patient care in tinea pedis?

OBJECTIVES: The aim of this study has been to evaluate patients with tinea pedis for their demographic data and attitudes affecting the treatment of disease, and to compare the in vitro activity of 10 antifungal agents and to relate them to their in vivo activity. METHODS: Patients with positive mycological examination were enrolled in the study, and a questionnaire comprised of 22 questions was administered. A mycological culture was carried out for each specimen. The antifungal susceptibility of the subcultured species was determined for griseofulvin, terbinafine, ciclopiroxolamine, fluconazole, ketoconazole, itraconazole, bifonazole, sulconazole, oxiconazole and miconazole with microdilution. RESULTS: Mycological cultures were carried out from 59 patients and there were 35 positive cultures (59.3%). The dermatophytes were Trichophyton rubrum (n = 25) and Trichophyton mentagrophytes (n = 3). The yeasts were Candida albicans (n = 7), Candida glabrata (n = 1) and Trichosporon (n = 2). In the minimum inhibitory concentration (MIC) study, the mean +/- standard error of the mean (SEM) MICs of the antifungals for T. rubrum were as follows: terbinafine 0.01 +/- 0.003, oxiconazole 0.16 +/- 0.05, sulkonazole 0.31 +/- 0.05, miconazole 0.45 +/- 0.15, itraconazole 0.74 +/- 0.01, ketokonazole 1.03 +/- 0.17, ciclopiroxolamine 1.30 +/- 0.12, bifonazole 1.94 +/- 0.51, griseofulvin 4.87 +/- 0.61, and fluconazole 17.91 +/- 3.67 microg/mL. CONCLUSION: Our study supports that azoles could be used as first-line treatment, as oxiconazole is very effective for both dermatophytes and C. albicans. Correlation between in vitro results and clinical outcomes of cases of dermatophytes is still to be established and interpretive breakpoints defined, in order to increase the quality of patient care in tinea pedis.

A novel mycological analysis valuable for evaluating therapeutic efficacy of antimycotics against experimental dermatophytosis in guinea pigs.

Although antimycotic effects are mainly evaluated with regard to whether or not the fungi grow from a specimen obtained from the drug-treated skin, the potential for discrepancies in skin specimens in which the fungi are grown has not been evaluated, in the experimental tinea model. In this study, to evaluate the therapeutic effectiveness of antimycotic agents against fungal skin infection, a novel form of mycological assessment, which focuses on the size of colonies grown from skin specimens was examined and developed. When microconidia of Trichophyton mentagrophytes were inoculated onto a Sabouraud dextrose agar (SDA) plate and incubated at 27 degrees C for 5 days, a linear relationship was observed between the growth area of mycelia and the logarithm of the quantity of microconidia. This relationship between the growth area and the logarithm of the number of T. mentagrophytes microconidia did not change with the addition of skin homogenate and/or keratin powder. Next, the number of fungi in skin blocks attendant upon experimental, cutaneous infection in guinea pigs was evaluated and analyzed via a calibration curve, determined based on a microconidium suspension of T. mentagrophytes. Estimates of severity of dermatophytic infection in experimental animals were parallel to, but more reliable than, results obtained via the conventional mycological method (fungus-positive skin ratio of treated skin) in culture studies of infected dermal tissues. This new analytical method may also be applicable to the in vivo assessment of the therapeutic effect against dermatophytosis experimentally produced in guinea pigs.

Efficacy of flutrimazole 1% powder in the treatment of tinea pedis.

The aim of the study was to compare the efficacy and tolerability of flutrimazole 1% powder vs. bifonazole 1% powder in treating tinea pedis. A multicentre, double blind, randomized, parallel and comparative study was conducted. Two hundred and twenty-two patients with clinically and mycologically confirmed tinea pedis were randomized to flutrimazole (n = 136) or bifonazole (n = 138) 1% powder applied twice daily for 4 weeks. The corresponding clinical cure rates were assessed at 2 and 4 weeks of treatment, and the global (clinical and mycological) cure rates were determined at the fourth week. Clinical cure rates were 83.5 and 82.4% for flutrimazole and bifonazole, respectively (95% CI: -0.0806 to 0.1009). Global cure rates were observed in 65.3 and 70.1% of patients treated with flutrimazole and bifonazole, respectively (95% CI: -0.0828 to 0.1779). Three non serious adverse events at the application site--itching (one patient per group) and dishydrotic eczema (one patient treated with flutrimazole)--were recorded during the study. These results support that flutrimazol 1% powder applied twice daily for a duration of 4 weeks is highly effective in the treatment of tinea pedis, showing a similar therapeutic profile with that of bifonazole 1% powder.