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Fungal disease affects over a billion people worldwide. Naamidine A inhibits the growth of diverse fungal pathogens through an unknown mechanism. Here, we show that the supplementation of medium with excess zinc abolishes the antifungal activity of naamidine A. Furthermore, we highlight that naamidine A has in vitro activity against terbinafine-resistant Trichophyton spp . and in vivo efficacy in a mouse model of dermatomycosis caused by T. mentagrophytes, highlighting its therapeutic potential as a topical treatment., Competing Interests: L.E.C. and L.W. are co-founders and shareholders in Bright Angel Therapeutics, a platform company for the development of novel antifungal therapeutics. L.E.C. is a Science Advisor for Kapoose Creek, a company that harnesses the therapeutic potential of fungi.

Deep dermatophytosis is a rare condition in which dermatophytes invade deep into the skin. Predisposing factors include chronic superficial dermatophytosis, immunosuppression or the use of topical steroids. Clinical, mycological, and histological examination are crucial for accurate diagnosis. Microscopy and culture or molecular diagnostic are useful tools when identifying the causative dermatophyte species. Species-directed systemic antimycotic treatment is golden standard and require careful consideration of potential drug-drug interactions and monitoring for both efficacy and side effects, as argued in this review., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Competing Interests: Declaration of interests We declare no competing interests.

Malassezia species are commensal fungi residing on the skin and in the gut of humans and animals. Yet, under certain conditions, they become opportunistic pathogens leading to various clinical conditions including dermatological disorders. The emergence of drug resistance and adverse effects associated with conventional antifungal agents has propelled the search for alternative treatments, among which phytomedicine stands out prominently. Phytochemicals, including phenolic acids, flavonoids, and terpenoids, demonstrate potential antifungal activity against Malassezia by inhibiting its growth, adhesion, and biofilm formation. Furthermore, the multifaceted therapeutic properties of phytomedicine (including anti-fungal and, antioxidant properties) contribute to its efficacy in alleviating symptoms associated with Malassezia infections. Despite these promising prospects, several challenges hinder the widespread adoption of phytomedicine in clinical practice mostly since the mechanistic studies and controlled experiments to prove efficacy have not been done. Issues include standardization of herbal extracts, variable bioavailability, and limited clinical evidence. Hence, proper regulatory constraints necessitate comprehensive research endeavors and regulatory frameworks to harness the full therapeutic potential of phytomedicine. In conclusion, while phytomedicine holds immense promise as an alternative or adjunctive therapy against Malassezia, addressing these challenges is imperative to optimize its efficacy and ensure its integration into mainstream medical care. In this review we provide an update on the potential phytomedicines in combating Malassezia-related ailments, emphasizing its diverse chemical constituents and mechanisms of action., Competing Interests: Declaration of competing interest The authors do hereby declare that they have no affiliations with or involvement in any organization or entity with any financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Non-tuberculous mycobacteria (NTM) are present widely in the natural environment and can invade the human body through the respiratory tract, gastrointestinal tract, and skin. Immunocompromised patients are particularly prone to infection, which primarily affects multiple organs, including the lungs, lymph nodes, and skin. However, cases of NTM bloodstream infections are rare. Here, we report a rare case of Mycobacterium marseillense bloodstream infection with concurrent skin fungal infection in a patient after kidney transplantation. Related literature was reviewed to enhance the understanding of this rare condition., Case Presentation: A 58-year-old male with a history of long-term steroid and immunosuppressant use after kidney transplantation presented with limb swelling that worsened over the past two months. Physical examination revealed redness and swelling of the skin in all four limbs, with a non-healing wound on the lower left limb. Skin tissue analysis by metagenomic next-generation sequencing (mNGS) and fungal culture indicated infection with Trichophyton rubrum. Blood culture results suggested infection with Mycobacterium marseillense. After receiving anti-NTM treatment, the patient's symptoms significantly improved, and he is currently undergoing treatment., Conclusion: Mycobacterium marseillense is a NTM. Gram staining suffered from misdetection, and the acid-fast staining result was positive. This bacterium was identified by mass spectrometry and mNGS analyses. Antimicrobial susceptibility tests for NTM were performed using the broth microdilution method. The results of the susceptibility test showed that Mycobacterium marseillense was sensitive to clarithromycin, an intermediary between moxifloxacin and linezolid. Bacterial clearance requires a combination of drugs and an adequate course of treatment. NTM bloodstream infections are relatively rare, and early identification and proactive intervention are key to their successful management., (© 2024. The Author(s).)

Background: Cryptococcosis is an infectious disease caused by encapsulated heterobasidiomycete yeasts. As an opportunistic pathogen, cryptococcal inhalation infection is the most common. While Primary cutaneous cryptococcosis is extremely uncommon., Case Presentation: A 61-year-old woman with a history of rheumatoid arthritis on long-term prednisone developed a red plaque on her left thigh. Despite initial antibiotic treatment, the erythema worsened, leading to rupture and fever. Microbiological analysis of the lesion's secretion revealed Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus epidermidis. Skin biopsy showed thick-walled spores, and culture confirmed primary cutaneous infection with Cryptococcus neoformans. Histopathological stains were positive, and mass spectrometry identified serotype A of the pathogen. The patient was treated with oral fluconazole and topical nystatin, resulting in significant improvement and near-complete healing of the skin lesion within 2.5 months., Conclusions: Primary cutaneous cryptococcosis was a primary skin infection exclusively located on the skin. It has no typical clinical manifestation of cutaneous infection of Cryptococcus, and culture and histopathology remain the gold standard for diagnosing. The recommended medication for Primary cutaneous cryptococcosis is fluconazole. When patients at risk for opportunistic infections develop skin ulcers that are unresponsive to antibiotic, the possibility of primary cutaneous cryptococcosis needs to be considered., (© 2024. The Author(s).)

Topical antifungals with activity against dermatophytes include amorolfine, allylamines, azoles, ciclopiroxolamine, and tolnaftate. Polyene antimycotics, such as amphotericin B and nystatin, alternatively, miconazole are suitable for yeast infections of the skin and mucous membranes. For severe yeast infections of the skin and mucous membranes, oral triazole antimycotics, such as fluconazole and itraconazole, are used. Pityriasis versicolor is treated topically with antimycotics, and in severe forms also orally with itraconazole, alternatively fluconazole. Terbinafine, itraconazole and fluconazole are currently available for the systemic treatment of severe dermatophytoses, tinea capitis and onychomycosis. In addition to proven therapeutic regimens, unapproved (off-label use) intermittent low-dose therapies are increasingly being used, particularly in onychomycosis. Oral antimycotics for the treatment of tinea capitis and onychomycosis in children and adolescents can only be used off-label in Germany. In general, any oral antifungal treatment should always be combined with topical antifungal therapy. In tinea corporis and tinea cruris caused by Trichophyton (T.) mentagrophytes ITS (internal transcribed spacer) genotype VIII (T. indotineae), there is usually terbinafine resistance. Identification of the species and genotype of the dermatophyte and resistance testing are required. The drug of choice for T. mentagrophytes ITS genotype VIII dermatophytoses is itraconazole. In individual cases, treatment-refractory onychomycosis may be due to terbinafine resistance of T. rubrum. Here too, resistance testing and alternative treatment with itraconazole should be considered. Therapy monitoring should be carried out culturally and, if possible, using molecular methods (polymerase chain reaction). Alternative treatment options include laser application, and photodynamic therapy (PDT)., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Abstract: This article reports an elderly male patient with nodules and ulcers on the face and behind the left ear after trauma. Primary cutaneous cryptococcosis was confirmed using pathological biopsy, special staining, tissue culture, and fungal sequencing. The patient received a therapeutic intervention involving the administration of the antifungal agent itraconazole. Substantial amelioration of cutaneous manifestations was observed after a 3-month course of treatment. After an elapsed interval, the patient was diagnosed with esophageal tumor. Moreover, the literature on 33 patients with primary cutaneous cryptococcosis published in the past 10 years was also reviewed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Trichophyton indotineae is a recently identified dermatophyte that frequently causes extensive and persistent dermatomycosis, particularly tinea corporis, tinea cruris, and tinea faciei. The infection is frequently encountered in countries of the Indian subcontinent and surrounding areas. In Europe, T. indotineae has mainly been detected in patients with an epidemiological link to the aforementioned regions. Unlike dermatomycoses caused by other dermatophyte species, infections caused by T. indotineae often exhibit treatment failure with commonly prescribed antifungal drugs. Reduced susceptibility to terbinafine is often observed in T. indotineae . In addition, reduced susceptibility to itraconazole has also been reported. Due to the extensive and persistent nature of the infection, as well as the reduced susceptibility to antifungal drugs, international experts recommend aggressive treatment of T. indotineae using a combination of oral and topical antifungals. Susceptibility testing may be warranted to guide treatment decisions. Early recognition of T. indotineae infections is crucial to prevent prolonged recurrences.

Dermatomycosis or superficial mycosis is considered one of the chronic fungal infections and a global challenge for the public health system. The severity of dermatomycosis is proportionately increasing with the emerging population of immunocompromised individuals, and it is becoming more prevalent, even life-threatening, in several tropical countries. In this context, improper long-term treatment with synthetic antifungal drugs and their related side effects imposes additional challenges in treating dermatomycosis. Thus, the present scenario highlights the need for a novel and accurate treatment with minimal or no side effects. The multifaceted therapeutic properties of various natural products have garnered the interest of scientific communities in recent years. Generally, plant-based products have low toxicity levels and offer diverse formulations and unique biomolecules for clinical applicability against dermatomycosis. Thus, this study presents an overview of the pathogenesis and different treatment strategies for dermatomycosis. In addition, we highlight the implementation of natural products of plant origin for treating dermatomycosis infections and reducing adverse events. Further, their mode of action and role in the development of pharmaceutical drugs are discussed., (© 2024 the International Society of Dermatology.)

The present study analyses the clinical characteristics of patients diagnosed with cutaneous fusarium through a systematic review of cases reported in literature. A total of 39 cases were included, of which 53% were men, 30% were women, and in 17% the sex was not specified. The age ranged from 5 to 85 years. Most cases were reported in Brazil, followed by Japan and United States of America. The most common agent was Fusarium solani, in 37.5% of the patients. Most of the affected individuals had acute myeloid leukaemia and some of the predisposing factors, which included induction chemotherapy, febrile neutropenia, and bone marrow transplantation. The clinical topography of the lesions was located in 27.5% and disseminated in 72.5%, with the most observed clinical feature outstanding the presence of papules and nodules with central necrosis in 47% of the cases. Longer survival was demonstrated in those treated with more than three antifungals. It is concluded that cutaneous fusarium is a complex and challenging clinical entity, infection in patients with leukaemias underscores the need for thorough care to decrease morbidity and mortality., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Abstract: Fungal infection is a rare condition in immunocompetent individuals, and it is associated with high rates of morbidity and mortality. We report on a case of cutaneous phaeohyphomycosis in healthy 25-year-old man. Based on the clinical findings, the case was first thought to be cervico-facial actinomycosis, but Alternaria was identified on the culture after debridement. Simple surgical excision resulted in the complete cure without administration of systemic antifungals., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Background: Current treatment options for Malassezia folliculitis (MF) are limited. Recent research has demonstrated the inhibitory effect of cold atmospheric plasma (CAP) on the growth of Malassezia pachydermatis in vitro, suggesting CAP as a potential therapeutic approach for managing MF., Objectives: The objective of our study is to assess the in vitro antifungal susceptibility of Malassezia yeasts to CAP. Additionally, we aim to evaluate the efficacy and tolerability of CAP in treating patients with MF., Methods: We initially studied the antifungal effect of CAP on planktonic and biofilm forms of Malassezia yeasts, using well-established techniques such as zone of inhibition, transmission electron microscopy, colony count assay and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt assay. Subsequently, a randomized (1:1 ratio), active comparator-controlled, observer-blind study was conducted comparing daily CAP therapy versus itraconazole 200 mg/day for 2 weeks in 50 patients with MF. Efficacy outcomes were measured by success rate, negative microscopy rate and changes in Dermatology Life Quality Index (DLQI) and Global Aesthetic Improvement Scale (GAIS) scores. Safety was assessed by monitoring adverse events (AEs) and local tolerability., Results: In laboratory investigations, CAP time-dependently inhibited the growth of Malassezia yeasts in both planktonic and biofilm forms. Forty-nine patients completed the clinical study. At week 2, success was achieved by 40.0% of subjects in the CAP group versus 58.3% in the itraconazole group (p = 0.199). The negative direct microscopy rates of follicular samples were 56.0% in the CAP group versus 66.7% in the itraconazole group (p = 0.444). No significant differences were found in the proportion of subjects achieving DLQI scores of 0/1 (p = 0.456) or in the GAIS responder rates (p = 0.588) between the two groups. Three patients in the CAP group and one patient in the itraconazole group reported mild AEs., Conclusion: CAP demonstrated significant antifungal activity against Malassezia yeasts in vitro and exhibited comparable efficacy to itraconazole in treating MF patients. Without the associated adverse effects of oral antifungal drugs, CAP can be considered a promising and safe treatment modality for MF., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Fusarium and allied genera (fusarioid) species are common colonizers of roots and aerial plant parts, or act as phytopathogens in forestry and horticultural or grain crops. However, they can also cause a wide range of infections in humans, including onychomycosis, cutaneous and invasive infections. Fusarioid keratitis is characterized by an infection of the cornea with a suppurative and ulcerative appearance, which may cause damage to vision and permanent blindness. The aim of the present study was to investigate the prevalence of fusarioid species, biofilm formation and antifungal susceptibility profiling of clinical isolates recovered from patients with keratitis and dermatomycoses., Methodology/principal Findings: The study was performed between March, 2012-December, 2022. Demographic, clinical and epidemiological data of patients were also collected. In the present study, most of the patients with keratitis were male (74%), had a median age of 42 years old, worked with plant material or debris and 26% of them reported eye trauma. Regarding dermatomycosis, most of patients were female and exhibited toenail lesions. Forty-seven isolates belonged to the genus Neocosmospora (78.33%), nine to the Fusarium fujikuroi (15%) and four to the Fusarium oxysporum (6.66%) species complexes. Several strains were moderate biofilm producers, specifically among Fusarium annulatum. Most strains showed increased MICs to amphotericin B and ketoconazole and low MICs to itraconazole. MICs ranged from 0.25 to 16 μg/mL for amphotericin B, 0.0625 to >16 μg/mL for ketoconazole and 0.125 to 8 for itraconazole., Conclusions/significance: It is possible to conclude that fusarioid keratitis in Northeastern Brazil is an important and neglected disease, given the high number of cases, increased need for keratoplasty and poor outcome of the disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ferreira da Cunha Neto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Malassezia pachydermatis is often reported as the causative agent of dermatitis in dogs. This study aims to evaluate the in vitro and in vivo antifungal activity of azoles and terbinafine (TRB), alone and in combination with the 8-hydroxyquinoline derivatives (8-HQs) clioquinol (CQL), 8-hydroxyquinoline-5-(n-4-chlorophenyl)sulfonamide (PH151), and 8-hydroxyquinoline-5-(n-4-methoxyphenyl)sulfonamide (PH153), against 16 M. pachydermatis isolates. Susceptibility to the drugs was evaluated by in vitro broth microdilution and time-kill assays. The Toll-deficient Drosophila melanogaster fly model was used to assess the efficacy of drugs in vivo. In vitro tests showed that ketoconazole (KTZ) was the most active drug, followed by TRB and CQL. The combinations itraconazole (ITZ)+CQL and ITZ+PH151 resulted in the highest percentages of synergism and none of the combinations resulted in antagonism. TRB showed the highest survival rates after seven days of treatment of the flies, followed by CQL and ITZ, whereas the evaluation of fungal burden of dead flies showed a greater fungicidal effect of azoles when compared to the other drugs. Here we showed for the first time that CQL is effective against M. pachydermatis and potentially interesting for the treatment of malasseziosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

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.

Cutaneous fungal infections affect millions around the world. However, severe, multi-resistant fungal infections are increasingly being reported over the past years. As a result of the high rate of resistance which urged for drug repurposing, statins were studied and found to have multiple pleiotropic effects, especially when combined with other already-existing drugs. An example of this is the synergism found between several typical antifungals and statins, such as antifungals Imidazole and Triazole with a wide range of statins shown in this review. The main mechanisms in which they exert an antifungal effect are ergosterol inhibition, protein prenylation, mitochondrial disruption, and morphogenesis/mating inhibition. This article discusses multiple in vitro studies that have proven the antifungal effect of systemic statins against many fungal species, whether used alone or in combination with other typical antifungals. However, as a result of the high rate of drug-drug interactions and the well-known side effects of systemic statins, topical statins have become of increasing interest. Furthermore, patients with dyslipidemia treated with systemic statins who have a new topical fungal infection could benefit from the antifungal effect of their statin. However, it is still not indicated to initiate systemic statins in patients with topical mycotic infections if they do not have another indication for statin use, which raises the interest in using topical statins for fungal infections. This article also tackles the different formulations that have been studied to enhance topical statins' efficacy, as well as the effect of different topical statins on distinct dermatologic fungal diseases., (© 2024 the International Society of Dermatology.)

Background: No reports have compared the clinical therapeutic efficacy of fluconazole and itraconazole in canine Malassezia dermatitis., Objectives: The study aimed to compare the clinical therapeutic efficacy of fluconazole and itraconazole and to evaluate the adverse effects of fluconazole in canine Malassezia dermatitis., Animals: Sixty-one client-owned dogs with Malassezia dermatitis., Materials and Methods: The enrolled animals were randomly divided into groups receiving 5 mg/kg fluconazole (5FZ), 10 mg/kg fluconazole (10FZ) or 5 mg/kg itraconazole (5IZ). The drugs were orally administered once daily for 28 days. Cytological examination, clinical index score (CIS), pruritus Visual Analog Scale (PVAS) evaluation and blood analysis (for 5FZ only) were performed on Day (D)0, D14 and D28., Results: On D14, significant reductions in mean yeast count (MYC), CIS and PVAS were observed in the 5FZ (n = 20, p < 0.01), 10FZ (n = 17, p < 0.01) and 5IZ (n = 16, p < 0.05) groups. In all three groups, a significant reduction (p < 0.001) in MYC, CIS and PVAS expression was observed on D28. There was no significant difference in the percentage reduction of MYC, CIS and PVAS among the groups. Moreover, there was a significant difference (p < 0.05) in each group between D14 and D28, except for the percentage reduction in MYC in the 10FZ and 5IZ groups. No adverse effects of fluconazole were observed in the 5FZ or 10FZ groups., Conclusions and Clinical Relevance: This study indicates that 5FZ and 10FZ are as effective as itraconazole in canine Malassezia dermatitis., (© 2024 ESVD and ACVD.)

Head and neck dermatitis (HND) is a form of atopic dermatitis (AD) that affects the seborrheic areas of the body and causes greater quality of life detriments than other types of AD. HND can be challenging to treat since first-line topical therapies may be ineffective or intolerable for long-term use on areas affected by HND while dupilumab may cause dupilumab-associated HND (DAHND). Current evidence implicates fungi, particularly Malassezia spp., in the pathogenesis of HND. Penetration of fungal antigens through the defective AD skin barrier activates the innate and adaptive immune systems to cause cutaneous inflammation via the T helper (Th)17 and/or Th2 axes. Malassezia sensitization may distinguish HND from other forms of AD. Multiple double-blind, placebo-controlled trials have shown antifungals to benefit HND, yet the persistence of symptom relief with sustained use remains unclear. Oral antifungals appear more effective than topical antifungals but may be harmful with long-term use. DAHND may also be fungal-mediated given improvement with antifungals and evidence of an overactive immune response against Malassezia in these patients. Janus kinase inhibitors are effective for HND, including DAHND, but may cause significant side effects when administered systemically. OX40/OX40L inhibitors and tralokinumab may be promising options for HND on the horizon. Demographic and environmental factors influence the host mycobiome and should be considered in future precision-medicine approaches as microbiome composition and diversity are linked to severity of HND., (© 2024. The Author(s).)

Background: Lagenidium deciduum is an oomycete that can cause infections in mammals that present similarly to pythiosis and mucormycosis. Most of the existing case reports have occurred in canines and have been fatal. In animals, medical therapy has not been successful, so surgical excision is the mainstay of treatment. Lagenidium sp. infections in humans are rare. There is only one case of a human Lagenidium sp. infection in the literature, and it presented as an ocular infection. The human ocular infection was resistant to medical therapy and required a penetrating keratoplasty for cure. Additional reports of effective therapy are needed to guide management of this emerging pathogen. We present the first case of a cutaneous Lagenidium deciduum infection in a human patient, which is also the first documented case of a Lagenidium deciduum infection in an immunocompromised host of any species., Case Presentation: An 18-year-old female with relapsed acute myeloid leukemia, awaiting a haploidentical stem cell transplant, presented with erythematous cutaneous lesions on her left hip and bilateral buttocks that enlarged and blackened over several days. About 1 week later, boil-like lesions appeared on her bilateral buttocks. The skin lesions were initially presumed to be bacterial in origin, so the patient was treated with clindamycin and cefepime with little improvement. Upon further investigation, fungal cultures and skin biopsies revealed aseptate hyphae, so the patient was switched to isavuconazole and amphotericin B due to concern for mucormycosis. Phenotypic characterization and DNA sequencing were performed by the Fungus Testing Laboratory, University of Texas Health Science Center at San Antonio, which identified the causal fungal organism as Lagenidium deciduum. All of her cutaneous lesions were surgically excised, and the patient was treated with micafungin, terbinafine, doxycycline, and azithromycin. Micafungin and terbinafine were continued until she achieved engraftment post-transplant., Conclusions: We report the first successful treatment of a human Lagenidium infection in an immunocompromised host through a combination of aggressive surgical excision and prolonged antifungal therapy during the prolonged neutropenia associated with allogeneic stem cell transplant. Prompt diagnosis and management may prevent disseminated oomycosis., (© 2024. The Author(s).)

Mucormycosis is a rare opportunistic infection caused by Mucorales fungi. Cutaneous mucormycosis typically present as chronic indolent infection, whereas rhino-orbital mucormycosis is rapidly progressive disease often invade the adjacent cerebral tissue associated with high mortality. This case represents the atypical clinical history of rhino-orbital-cutaneous mucormycosis. The patient was presented with a right orbital cellulitis associated with an extensive multiple suppurative deep cutaneous infection and worsening headache. The skin lesion was initiated from a localized abscess at the right periorbital area nine months before admission. Suspicion of fungal infection was raised after weeks of non-responsive antibiotics treatment. Aggressive treatment with exoneration of the right eye and surgical debridement was undertaken. Periodic acid Schiff staining from healthy periorbital tissue revealed ribbon-like hyphae with pauciseptate and 90° branching identified as Mucoraceaefamily. The resolution was seen after four weeks of antifungal treatment with Amphotericin B., Competing Interests: The authors declare no competing interest., (Copyright: Ni Putu Ayu Reza Dhiyantari et al.)

Background: The incidence of Talaromyces marneffei (T. marneffei) infection has increased in recent years with the development of organ transplantation and the widespread use of immunosuppressive agents. However, the lack of clinical suspicion leading to delay or misdiagnosis is an important reason for the high mortality rate in non-human immunodeficiency virus (HIV) and non-endemic population. Herein, we report a case of disseminated T. marneffei infection in a non-HIV and non-endemic recipient after renal transplant, who initially presented with skin rashes and subcutaneous nodules and developed gastrointestinal bleeding., Case Presentation: We describe a 54-year-old renal transplantation recipient presented with scattered rashes, subcutaneous nodules and ulcerations on the head, face, abdomen, and right upper limb. The HIV antibody test was negative. The patient had no obvious symptoms such as fever, cough, etc. Histopathological result of the skin lesion sites showed chronic suppurative inflammation with a large number of fungal spores. Subsequent fungal culture suggested T. marneffei infection. Amphotericin B deoxycholate was given for antifungal treatment, and there was no deterioration in the parameters of liver and kidney function. Unfortunately, the patient was soon diagnosed with gastrointestinal bleeding, gastrointestinal perforation and acute peritonitis. Then he rapidly developed multiple organ dysfunction syndrome and abandoned treatment., Conclusions: The risk of fatal gastrointestinal bleeding can be significantly increased in kidney transplant patients with T. marneffei infection because of the long-term side effects of post-transplant medications. Strengthening clinical awareness and using mNGS or mass spectrometry technologies to improve the detection rate and early diagnosis of T. marneffei are crucial for clinical treatment in non-HIV and non-endemic population., (© 2024. The Author(s).)

BACKGROUND Histoplasmosis is typically associated with immunocompromised individuals, but cases in immunocompetent patients are rare. Primary cutaneous histoplasmosis (PCH) is a challenging diagnosis due to its clinical polymorphism and can mimic other infectious and non-infectious diseases. Previous cases of PCH have been reported in immunocompetent patients with underlying medical conditions or trauma history. So far there have been no reports of PCH after platelet-rich plasma (PRP) application due to inadequate hygiene measures in an immunocompetent host. CASE REPORT This case report presents a rare occurrence of PCH following a cosmetic procedure (PRP injection) in an immunocompetent patient. The patient developed nodule-like lesions at the application sites, which progressed to ulceration with purulent discharge. Initially, atypical mycobacterial infection was suspected, and empirical antibiotic therapy was initiated. Complementary tests were performed, ruling out immunosuppression and systemic pathogens. The patient showed complete resolution of the lesions after one month of atypical treatment with trimethoprim-sulfamethoxazole (TMP/SMX). Pathological examination confirmed the diagnosis of PCH with intracytoplasmic inclusions of Histoplasma sp. CONCLUSIONS This case highlights the importance of considering histoplasmosis as a diagnostic possibility, especially in hyperendemic areas like Venezuela. Direct inoculation of Histoplasma sp. after aesthetic procedures without proper hygiene measures can lead to pathological lesions, even in immunocompetent individuals. TMP/SMX can be considered as an alternative treatment option in the absence of the first-line medication. Further exploration of this treatment approach may benefit patients with similar clinical conditions or when ideal treatment options are unavailable.

Primary cutaneous mucormycosis is caused by environmental fungi and may complicate leg ulcers or traumatic wounds even in immunocompetent individuals. This case report highlights recurrent lower limb ulcers and cellulitis in a patient with type two diabetes mellitus, which was unresponsive to conventional antibiotic treatment. Histopathology revealed the diagnosis of cutaneous mucormycosis, and fungal cultures identified Rhizopus variabilis as the causative organism. Initial courses of oral azole antifungals yielded only partial response and he eventually required more aggressive treatment with i.v. amphotericin B and oral posaconazole. Good treatment outcomes for this condition require a high index of clinical suspicion, early histopathological and microbiological diagnosis, targeted systemic antifungal therapy, and surgical debridement if necessary.

Antifungal stewardship refers to the rational use of antifungal agents. Historically, in some instances, the misuse or overuse of antifungal agents has predisposed patients to an elevated risk of systemic side-effects and treatment resistance, as well as increased healthcare costs. Superficial mycoses, such as onychomycosis, are sometimes treated without any diagnostic testing and is associated with a high likelihood of self-diagnosis and self-treatment, potentially leading to the emergence of resistance against commonly used antifungals like terbinafine. Practitioners need to ensure that a proper clinical diagnosis is backed up by appropriate testing. This may include the traditional light microscopy and culture; additionally, molecular techniques (such as polymerase chain reaction, terbinafine gene mutational analysis) and antifungal susceptibility testing are considerations as appropriate. The choice of antifungal agent should be guided by what is the standard of care in the location where the clinician practices as well as more broadly state and national prescription patterns. Recently, reports of treatment resistance concerning both superficial and deep fungal infections have added another layer of difficulty to clinical practice. This review aims to explore the phenomenon of antifungal drug resistance, and highlights the importance of adopting antifungal stewardship programs. We provide an overview of treatment resistance and mechanisms of resistance reported thus far in dermatophytes. Challenges of performing antifungal susceptibility testing and therapeutic drug monitoring are discussed, as well as principles, recommendations and future directions of antifungal stewardship programs.

Malassezia are members of the mycobiome of dogs and cats. In the presence of an underlying disease, these yeasts can proliferate, attach to the skin or mucosa to induce a secondary Malassezia dermatitis, otitis externa or paronychia. Since allergic dermatitis is one of the most common underlying causes, diagnostic investigation for allergy is often indicated. Cats may suffer from various other underlying problems, especially where Malassezia dermatitis is generalised. Malassezia dermatitis in dogs and cats is chronic, relapsing and pruritic. Direct cytology from dermatological lesions and the ear canal, showing "peanut-shaped" budding yeasts, facilitates a rapid and reliable diagnosis. Topical treatment includes antiseptic and antifungal azole-based products. Systemic treatment with oral antifungals is indicated only in severe or refractory disease. Identification and treatment of the underlying cause is essential for an optimal response. In this evidence-based narrative review, we discuss the clinical presentation of Malassezia dermatitis in dogs and cats, underlying comorbidities, and diagnostic considerations. Treatment is discussed in light of emerging evidence of antifungal resistance and the authors' clinical experience., Competing Interests: Declaration of Competing Interest Ralf Mueller has been a consultant, lectured for or received support for research from the following companies manufacturing or selling antifungal medications: Ceva (topical chlorhexidine), Elanco (Malaseb shampoo, itraconazole), Selectavet (enilconazole) and Virbac (topical chlorhexidine). None of the other authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Fungi are opportunistic eukaryotic entities often taking advantage of susceptibilities offered by a host due to its immunocompromised status, changed microbiome, or ruptured physical barriers and eventually cause infections. They either invade the skin superficially or are deep-seated. Superficial mycosis affects the skin, hair, and nails inhabiting the outermost layer, stratum corneum. In the present study, we report a case of superficial mycosis (onychomycosis in particular) in a 45-year-old immunocompetent man who was an ex-defense personnel and presently serving as a security guard at the University of Jammu, District Jammu, Jammu and Kashmir, India. The infection evolved 17 years ago and negatively affected the quality of life of the patient. For the identification of the causal agent, direct microscopy, cultural, micro-morphological, molecular characterization (ITS sequencing), and phylogenetic analysis were taken into account. A mucoralean fungal species, Thamnostylum piriforme, was isolated from the fingernails (left hand) of the investigated patient, which represents a new global report as the causal agent of superficial mycosis. In vitro antifungal susceptibility testing showed T. piriforme sensitivity to itraconazole, amphotericin B and ketoconazole while resistance to fluconazole. Careful selection of optimal therapy for fungal infection based primarily on correct identification and antifungal susceptibility testing could provide effective results during treatment against these opportunistic human fungal pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite the increasing interest in studying the gut mycobiota of dogs, the association between fungal colonization and the development of digestive disorders in this species remains largely understudied. On the other hand, the high prevalence of antifungal-resistant yeasts detected in previous studies in samples from animals represents a major threat to public health. We analyzed the presence of culturable yeasts in 112 rectal swab samples obtained from dogs with digestive disorders attended in a veterinary teaching hospital. Our results revealed that Malassezia pachydermatis was frequently isolated from the studied dog population (33.9% of samples), and that the isolation of this yeast was significantly associated to the age of animals, but not to their sex, disease group, or the presence of vomits and/or diarrhea. In contrast, other yeast species were less prevalent (17.9% of samples in total), and their isolation was not significantly associated to any variable included in the analysis. Additionally, we observed that 97.5% of the studied M. pachydermatis isolates (n = 158, 1-6 per positive episode) displayed a minimum inhibitory concentration (MIC) value >4 μg/ml to nystatin, 31.6% had a MIC ≥32 μg/ml to fluconazole, and 27.2% had a MIC >4 μg/ml to amphotericin B. The antifungal susceptibility profiles of non-Malassezia (n = 43, 1-7 per episode) were more variable and included elevated MIC values for some antifungal-species combinations. These results confirm that the intestine of dogs is a reservoir of opportunistic pathogenic yeasts and suggest that the prevalence of M. pachydermatis colonization depends more on the age of animals than on any specific digestive disorder., Competing Interests: Declaration of competing interest None of the authors of this paper has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There is increasing evidence of clinically resistant cutaneous fungal infections. The use of combination oral antifungals is described in adults but not in paediatric patients. We present seven paediatric cases of clinically resistant fungal infections treated successfully with combination oral antifungal therapy after inadequate response to a single agent., (© 2023 The Australasian College of Dermatologists.)

Deep cutaneous mycoses (DCMs) are rare infections that extend throughout the dermis and subcutis, often occurring after inoculation with pathogenic fungi. Trends toward a growing incidence have been observed that may be partially related to an increasing population of solid organ transplant patients. The aim of this study is to describe the diagnostics and the outcomes of DCM among kidney transplant recipients so as to optimize their management. We performed a retrospective review of cases of DCM occurring among kidney transplant recipients in our institution over 12 years. Twenty cases were included. Lesions were only located on the limbs and presented mainly as single (10/20, 50%) nodular lesions (15/20, 75%), with a mean size of 3 cm. Direct mycological examination was positive for 17 patients (17/20, 85%) and the cultures were consistently positive. Thirteen different fungal species were observed, including phaehyphomycetes (n = 8), hyalohyphomycetes (n = 3), dermatophytes (n = 1), and mucorale (n = 1). The (1-3) beta-D-glucan antigen (BDG) was also consistently detected in the serum (20/20, 100%). Systematic imaging did not reveal any distant infectious lesions, but locoregional extension was present in 11 patients (11/14, 79%). Nineteen patients received antifungal treatment (19/20, 95%) for a median duration of 3 months, with surgery for 10 (10/20, 50%). There is a great diversity of fungal species responsible for DCMs in kidney transplant recipients. The mycological documentation is necessary to adapt the antifungal treatment according to the sensitivity of the species. Serum BDG positivity is a potentially reliable and useful tool for diagnosis and follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Brazil-grown outdoor-cultivated Agaricus brasiliensis KA21 fruiting body (KA21) significantly increases the production of serum anti-beta-glucan antibody. Therefore, KA21 ingestion may be useful for the prevention and alleviation of fungal infections. This study aimed to determine the effects of KA21 in fungal infections in animals. KA21 was administered to nine dogs infected with Malassezia. Notably, the anti-beta-glucan antibody titer remained unchanged or tended to decrease in the oral steroid arm, whereas in the non-steroid arm, antibody titer increased in almost all animals after KA21 ingestion. Dogs showing improved clinical symptoms exhibited increased anti-beta-glucan antibody titers. The results of this study suggest that KA21 ingestion may alleviate the symptoms of Malassezia and other fungal infections and that continuous ingestion may help prolong recurrence-free intervals. Additionally, the ingestion of KA21 during oral steroid dosage reduction or discontinuation may enable smoother steroid withdrawal.

Microsporum canis is considered the common dermatophyte agent associated with ringworm in felines and canines. In the present study, we sampled n = 548 felines and canines for the probable isolation of M. canis. The rate of isolation from the cats and dogs was 70.27 % (52/74) and 1.68 % (8/474), respectively and Persian cats were found to be highly susceptible to M. canis infection. The strains were evaluated for their production of phospholipase, lipase, catalase, and hemolysis and their ability to grow at 35 ℃. All the strains were identified as low producers of catalase and n = 17 strains exhibited high thermotolerance ability. Terbinafine was found to be the most effective antifungal drug and fluconazole was the least effective, in vitro. AFLP analysis revealed three genotypes of M. canis with 15 sub-clusters showing ≥ 90 % similarity and 7 sub-clusters exhibiting 100 % similarity. However, the phenotypic characters cannot be attributed based on the AFLP profiles., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Dermatomycoses are typical hair, skin, or nail infections caused mainly by dermatophytes and nondermatophytes: Trichophyton, Microsporum, Epidermophyton, and Candida. In addition to the esthetical impact, pain, and nail deformity, these mycoses can be a source of severe disease. The high cost of treatment, toxicity, and the emergence of resistant infectious agents justifies research into new drugs. This work evaluates the fungicidal activity of nanocomposites (NCs) based on reduced graphene oxide (rGO) loaded with silver (Ag) nanoparticles (rGO/Ag) against clinical isolates of dermatophytes and Candida species. This is an unprecedented study in which, for the first time, hybrid nanocompounds based on Ag/rGO were tested against Epidermophytom, Microsporum, and Trichophyton species (dermatophytes agents). In this paper, we synthesize rGO using different concentrations of Ag by hydrolysis of metal salt AgNO 3 and follow the growth of nanocrystals on sheets of rGO provided by the NaBH 4 . The NCs were analyzed by X-ray diffraction analysis, and the NC morphology, silver distribution on the rGO surface, and crystalline information were investigated by transmission electron microscopy. Antifungal susceptibility assay was performed by the microdilution method based on modified Clinical and Laboratory Standards Institute (CLSI) protocol. Time-kill kinetics was conducted to monitor the effect of the composite to inhibit fungal cells or promote structural changes, avoiding germination. The toxicological evaluation of the NCs was born in an in vivo model based on Galleria mellonella (G. mellonella) . Minimum inhibitory concentration (MIC) values of the rGO/Ag NCs ranged from 1.9 to 125 μg/mL. The best inhibitory activity was obtained for rGO/Ag12%, mainly against Candida spp. and Epidermophyton floccosum . In the presence of sorbitol, MIC values of rGO/Ag NCs were higher (ranging from 15.6 to 250 μg/mL), indicating the action mechanism on the cell wall. Both yeast and dermatophytes clinical isolates were inhibited at a minimum of 6 and 24 h, respectively, but after 2 and 12 h, they had initial antifungal interference. All hybrid formulations of rGO/Ag NCs were not toxic for G. mellonella . This study provides insights into an alternative therapeutic strategy for controlling dermatomycoses.

Fungal infections are a challenging to treat cutaneous condition. Approximately 20-25% of humans are affected by superficial fungal infections that invade and multiply within keratinized tissues. To compare the efficacy of either terbinafine or itraconazole orally versus the combination of the two drugs in the treatment of recalcitrant dermatophytosis. The current study included 45 patients with recalcitrant dermatophytosis who were distributed into 3 groups (each of 15 patients); Group A received terbinafine 250 mg twice a day for 4 weeks. Group B received itraconazole 200 mg twice a day for 4 weeks. Group C received terbinafine 250 mg once daily and itraconazole 200 mg once daily for 4 weeks. The patients were followed up for 12 weeks after initiation of treatment by clinical and microbiological assessment to determine the cure rate. At the end of twelve weeks, 12 (80%) patients in group A; 13 (86.7%) patients in group B and 15 (100%) patients in group C were completely cured. Despite of cure rates being higher in the combined group C; yet results were not statistically significant (p = 0.207). Clinical cure rates were non significantly higher in itraconazole + terbinafine combined group (p = 0.207). Combination of terbinafine and itraconazole had a higher clinical and mycological cure rate when compared to the use of either drug alone as monotherapy. Further randomized, multicenter, large cohort studies are warranted to validate the use of combination antifungal treatments., (© 2023. The Author(s).)

According to estimates, up to 25% of the world's population has fungal skin diseases, making them the most prevalent infectious disease. Several chemical classes of antifungal drugs are available to treat fungal infections. However, the major challenges of conventional formulations of antifungal drugs include poor pharmacokinetic profiles like solubility, low permeability, side effects and decreased efficacy. Novel drug delivery is a promising approach for overcoming pharmacokinetic limitations and increasing the effectiveness of antibiotics. In this review, we have shed light on microemulsions, nanoemulsions, and emulgels as novel drug delivery approaches for the topical delivery of antifungal antibiotics. We believe these formulations have potential translational value and could be developed for treating fungal infections in humans.

Background: Subcutaneous mycoses caused by opportunistic filamentous fungi are emerging infections in developed countries due to the longer survival of immunocompromised patients. The evidence published in relation to subcutaneous mycoses is fundamentally based on case reports and small case series., Methods: We performed an observational retrospective study of subcutaneous mycoses caused by opportunistic filamentous fungi diagnosed at our institution between 2017 and 2022. This study aims to estimate the incidence rate of subcutaneous mycoses, identify which fungal species are involved, and analyse which clinical variables predispose to infection and if any are associated with mortality., Results: Fifteen patients met the inclusion criteria. The median age was 61 years (range 27-84), and 80% of them were males. Alternaria spp. were the most common fungi. Two other organisms were frequently isolated: Scedosporium apiospermum and Fusarium solani. Among patients infected with F. solani, 66.7% died. The most common clinical presentation was suppurative nodules in the lower limbs and the main risk factors for infection were immunosuppressants, corticosteroids, previous trauma and transplantation, but they were not particularly associated with increased mortality. A statistically significant association with mortality was only found in the case of positive blood culture (p = <.001)., Conclusions: Phaeohyphomycosis has a lower risk of dissemination, especially when compared to subcutaneous mycoses caused by hyalohyphomycetes. It is important to convey the severity of these skin infections to the physicians involved in the treatment and follow-up of susceptible patients to avoid misdiagnosis and delays in the treatment, especially in the case of hyalohyphomycosis., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Subcutaneous (deep) mycoses are a chronic infectious disease of the skin and underlying structures endemic in tropical countries. The disease has serious medical and socioeconomic consequences for patients, communities and health services in endemic areas. The inclusion of mycetoma and other subcutaneous mycoses in the list of Neglected Tropical Diseases by WHO highlights the need to assess the burden of these diseases and establish control programs where necessary. In Ethiopia no strategies can be devised because of a lack of epidemiologic information. To address this evidence gap, we performed a national rapid assessment of the geographic distribution of subcutaneous mycoses., Methodology: We conducted a rapid retrospective assessment using hospital records to identify all suspected and confirmed cases of subcutaneous mycoses in 13 referral hospitals across the country between 2015 and 2022. In each hospital the logbooks were reviewed for diagnoses of subcutaneous mycosess, as diagnosed per routine practice. Descriptive analysis was done., Result: From 13 hospitals we extracted 143 cases of subcutaneous mycoses, registered from July 2018 to September 2022. 118 (82.5%) patients were diagnosed as mycetoma, 21 (14.7%) as chromoblastomycosis and the remaining 4 (2.8%) as sporotrichosis. The mean age of patients was 35.8 years (SD = 14.5). 101 (70.6%) patients were male and 96 (67.1%) patients were farmers. 64 (44.8%) cases were from the Tigray regional state. 56 (65.9%) patients had information on diagnostic microscopic evaluation: for mycetoma histopathologic evaluation and fine needle aspiration cytology had a higher positivity rate while for chromoblastomycosis potassium hydroxide (KOH) staining had a better yield. The main clinical presentations were nodules, sinuses and infiltrative plaques on the skin. Radiologic findings of bone involvement was present in some., Conclusions: Mycetoma and other subcutaneous mycoses are endemic in Ethiopia, with cases reported from almost all regions with the highest cases numbers reported from the northern part of the country. A routine program and systems should be developed to identify and document the burden of subcutaneous fungal infections in the country. Diagnosis and treatment guidelines should be developed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Enbiale et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Antifungal resistance has become prevalent worldwide. Understanding the factors involved in spread of resistance allows the formulation of strategies to slow resistance development and likewise identify solutions for the treatment of highly recalcitrant fungal infections. To investigate the recent explosion of resistant strains, a literature review was performed focusing on four main areas: mechanisms of resistance to antifungal agents, diagnosis of superficial fungal infections, management, and stewardship. The use of traditional diagnostic tools such as culture, KOH analysis and minimum inhibitory concentration values on treatment were investigated and compared to the newer techniques such as molecular methods including whole genome sequencing, and polymerase chain reaction. The management of terbinafine-resistant strains is discussed. We have emphasized the need for antifungal stewardship including increasing surveillance for resistant infection., (© 2023 European Academy of Dermatology and Venereology.)

The Malassezia genus comprises lipid-dependent yeasts that have long been associated with common skin diseases, and have recently been linked with Crohn's disease and certain cancers. Understanding Malassezia susceptibility to diverse antimicrobial agents is crucial for identifying effective antifungal therapies. Here, we tested the efficacy of isavuconazole, itraconazole, terbinafine, and artemisinin against three Malassezia species: M. restricta , M. slooffiae, and M. sympodialis . Using broth microdilution, we found antifungal properties for the two previously unstudied antimicrobials: isavuconazole and artemisinin. Overall, all Malassezia species were particularly susceptible to itraconazole, with a MIC range from 0.007 to 0.110 μg/mL. IMPORTANCE The Malassezia genus is known to be involved in a variety of skin conditions and has recently been associated with diseases such as Crohn's disease, pancreatic ductal carcinoma, and breast cancer. This work was completed to assess susceptibility to a variety of antimicrobial drugs on three Malassezia species, in particular Malassezia restricta , which is an abundant Malassezia species both on human skin and internal organs and has been implicated in Crohn's disease. We tested two previously unstudied drugs and developed a new testing method to overcome current limitations for measuring growth inhibition of slow-growing Malassezia strains., Competing Interests: The authors declare no conflict of interest.