Malassezia dermatitis in dogs and cats.

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.

Thamnostylum piriforme, a novel etiological agent of superficial mycosis.

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.

Analysis of the culturable gut yeast microbiota of dogs with digestive disorders.

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.

Deep cutaneous mycoses in kidney transplant recipients: Diagnostic and therapeutic challenges.

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.

In vitro virulotyping, antifungal susceptibility testing and DNA fingerprinting of Microsporum canis strains of canine and feline origin.

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 â„ƒ. 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.

Combination oral antifungal therapy for paediatric fungal infection: An option to improve efficacy and overcome clinical resistance.

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.

Antifungal Activity of Nontoxic Nanocomposite Based on Silver and Reduced Graphene Oxide against Dermatophytes and Candida spp.

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 AgNO3 and follow the growth of nanocrystals on sheets of rGO provided by the NaBH4. 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.

Invasive Malassezia Infections.

The Malassezia species are dimorphic fungi that require lipids such as olive oil for their growth. They are constituents of the normal human skin microbiota and can affix to the host or other surfaces through the establishment of biofilms. Malassezia species are accountable for superficial mycoses like folliculitis. Additionally, they are capable of causing invasive infections, such as of the bloodstream, in neonates and immunocompromised patients, albeit infrequently. Catheter-associated bloodstream infections in neonates are the most commonly reported invasive cases. Remarkably, unlike other invasive fungal infections, neutropenia and the use of broad-spectrum antibiotics do not seem to contribute to the risk of invasive Malassezia infections. Nosocomial outbreaks of Malassezia infections have been reported. While most cases of invasive Malassezia infection are fungemia, they seldom give rise to disseminated lesions in various organs. The diagnosis can be confirmed by the visualization of characteristic yeasts through histologic or cytologic examination of a biopsy or needle aspiration specimen, or via positive culture results from sterile sites. The prognosis for invasive Malassezia infection is generally favorable, with few reports of treatment failure. Nevertheless, due to the limited number of cases, evidence-based treatment recommendations are wanting. Management of invasive Malassezia infections linked to central venous catheters includes removal of the catheter, cessation of intravenous lipid emulsion, and intravenous administration of appropriate antifungal agents.

Comparison between the efficacy of terbinafine and itraconazole orally vs. the combination of the two drugs in treating recalcitrant dermatophytosis.

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.

Microemulsions, nanoemulsions and emulgels as carriers for antifungal antibiotics.

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.

Fungi can make people sick and can be quite dangerous. They can cause infections on the skin and, if left untreated, they can get inside our bodies, which is not good. To treat these infections we use creams and lotions. But sometimes these creams don't work very well because the medicine does not dissolve properly, doesn't get into the skin or is unable to fully treat the fungal infection. So, instead of regular creams we can use mixtures called microemulsions, nanoemulsions and emulgels. These mixtures can be more effective at eliminating fungal infections on our skin. They work well and are an effective choice for treating these infections.

Part 1: Understanding the role of Malassezia spp. in skin disorders: Malassezia yeasts as commensal or pathogenic organisms of human and animal skin.

INTRODUCTION: Malassezia spp. are a group of lipid-dependent basidiomycetes yeasts acting as commensal organisms of the human and animal skin. However, under some not well-defined circumstances, these yeasts may switch to opportunistic pathogens triggering a number of skin disorders with different clinical presentations. The genus comprises of 18 lipid-dependent species with a variable distribution in the hosts and pathologies thus suggesting a host- and microbe-specific interactions. AREA COVERED: This review highlighted and discussed the most recent literature regarding the genus Malassezia as a commensal or pathogenic organisms highlighting Malassezia-associated skin disorders in humans and animals and their antifungal susceptibility profile. A literature search of Malassezia associated skin disorders was performed via PubMed and Google scholar (up to May 2023), using the different keywords mainly associated with Malassezia skin disorders and Malassezia antifungal resistance. EXPERT OPINION: Malassezia yeasts are part of the skin mycobiota and their life cycle is strictly associated with the environment in which they live. The biochemical, physiological, or immunological condition of the host skin selects Malassezia spp. or genotypes able to survive in a specific environment by changing their metabolisms, thus producing virulence factors or metabolites which can cause skin disorders with different clinical presentations.

Subcutaneous mycoses: Endemic but neglected among the Neglected Tropical Diseases in Ethiopia.

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.

Recalcitrant cutaneous fungal infections-A growing problem.

The incidence and prevalence of recalcitrant cutaneous fungal infections is on the rise. Terbinafine-resistant Trichophyton has not only been widespread in India, but has also been reported in countries spread throughout the globe. Strains of yeasts such as Malassezia and Candida, which exist both as commensals and as pathogens to the human skin, have also been found to develop resistance to antifungals. Non-dermatophyte moulds which can colonize and infect damaged nails are especially difficult to treat, not only due to resistance, but also because of poor drug penetration of hard keratin. Psychosocial factors such as the indiscriminate broad-spectrum antifungal use in agriculture and in medicine, and poor adherence to hygienic measures to break the chain of infection contribute to the development of antifungal resistance. Such environments encourage fungi to develop various resistance mechanisms to withstand antifungal treatment. These include: (a) alteration of the drug target, (b) increasing efflux of drug/metabolites, (c) inactivation of drug, (d) bypass mechanisms or substitution of the pathway affected by the drug, (e) stress adaptation mechanisms and (f) biofilm formation. Understanding of such mechanisms and how they arise are crucial for development of new ways to prevent or overcome resistance. Novel antifungal treatments have recently been approved in the United States of America for treatment of vulvovaginal candidiasis. Ibrexafungerp (enfumafungin derivative) and oteseconazole (tetrazole) differ from their respective related drug classes of echinocandins and triazoles by having different structures, which lend these medicines advantage compared to traditional treatment by having a different binding site and more selectivity for fungi respectively. Other drugs designed to circumvent the known mechanisms of antifungal resistance are also at various phases of development. Concurrent measures at an institutional and individual level to address and limit inappropriate antifungal use to reduce development of antifungal resistance should be undertaken in a concerted effort to address this epidemic.

Emerging subcutaneous mycoses by opportunistic filamentous fungi: A retrospective study in Northwest Spain.

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.

Current status and research progress of nanoparticle application in superficial fungal infection.

Superficial fungal infections (SFIs) are characterized by diverse etiologies, complex pathogenesis, and marked geographical differences in patient symptoms. Conventional management of SFIs is associated with complications such as hepatotoxicity, skin problems, severe headaches, and clinical difficulties including intractable relapses and drug-drug interactions in patients with chronic diseases remain to be addressed. Moreover, in topical treatment, low penetration of antifungal drugs in hard tissues such as finger (toe) nails and drug-resistant fungi are emerging concerns in current antifungal therapy. Nanotechnology has been a leading research topic in recent years for new dosing forms of antifungal drugs, chemical modification of traditional drugs, and pharmacokinetic improvement, providing potential opportunities for the effective treatment of SFIs. The present study reviewed the direct use of nanoparticles in SFIs and the use of nanoparticles as carriers in SFIs and discussed their future medicinal applications. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/01-12915-PM-29863.jpg.

Naftifine: A Topical Allylamine for Superficial Dermatophytosis.

Dermatophytosis is a very common public health problem with high prevalence. Dermatophytes are a highly specialized set of filamentous fungi, which are adapted to keratinized tissues of humans and animals. Dermatophytosis is the most common fungal infection worldwide, affecting approximately 20-25% of the world's population. The etiological agents of dermatophytosis, called dermatophytes, change with geography and socioeconomic status. Trichophyton rubrum (T. rubrum) is the prime species for skin and nail infections followed by T. mentagrophytes/ T. interdigital complex. There is a shift from T. rubrum to T. mentagrophytes in India for superficial fungal infections. In order to deal with fungal infections, treatment strategies involve the use of systemic antifungals and/or topical antifungal agents. Naftifine is a synthetic allylamine antifungal first reported in 1974 and in 1985 became the first commercially available allylamine. The highly lipophilic nature of allylamine allows efficient penetration and reasonably high concentrations in the stratum corneum (SC) and hair follicles. Naftifine is fungicidal as well as fungistatic. The higher efficacy rates of allylamines over imidazoles for the treatment of fungal infections, even for months after cessation of treatment, is thought to be due to their fungicidal effect, as well as to potentially greater keratin binding and slower release from the SC. The effectiveness of naftifine is also demonstrated against various bacteria belonging to both gram-negative and gram-positive classes. The antiinflammatory property of naftifine has been reported in various preclinical studies where it has been shown to target the prostaglandin pathway. Naftifine 1 and 2% gel and cream is approved by The United States Food and Drug Administration (USFDA), recently naftifine has been approved in India by the Indian regulatory authority Drug Controller General of India (DCGI) for the treatment of dermatophytosis. Naftifine 2% also appears to be a promising treatment, requiring fewer applications than the 1% formulation. Naftifine appears to be effective in a single dose and has a shorter treatment duration than azoles. Naftifine demonstrated its efficacy and safety in various clinical studies of tinea infections. Naftifine offers a very useful and promising option for treating dermatophytosis.