UNASSIGNED: 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.
UNASSIGNED: This article reviews the clinical evidence, safety, dosage regimens, pharmacokinetics, and management algorithm of new-generation azole antifungals.
UNASSIGNED: 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.

UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

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.

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.

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.

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.
OBJECTIVE: To identify factors contributing to difficult to treat recurrent superficial fungal infections.
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).
CONCLUSIONS: 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.

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.