Sporotrichosis is a superficial fungal disease that can affect animals and humans. The high number of infected cats has been associated with zoonotic transmission and contributed to sporotrichosis being considered by the World Health Organization as one of the main neglected tropical fungal diseases for 2021-2030. Oral administration of itraconazole (ITZ) is the first choice for treatment, but it is expensive, time-consuming, and often related to serious adverse effects. As a strategy to optimize the treatment, we proposed the development of a hydrophilic gel with nanomicelles loaded with ITZ (HGN-ITZ). The HGN-ITZ was developed using an I-optimal design and characterized for particle size, Zeta potential, drug content, microscopic aspects, viscosity, spreadability, in vitro drug release, in vitro antifungal activity, and clinical evaluation in cats. The HGN-ITZ showed a high content of ITZ (97.3 ± 2.1 mg/g); and characteristics suitable for topical application (viscosity, spreadability, globules size, Zeta potential, controlled drug release). In a pilot clinical study, cats with disseminated sporotrichosis were treated with oral ITZ or HGN-ITZ + oral ITZ. A mortality rate of 21.3% was observed for the oral ITZ group compared to 5.3% for the HGN-ITZ + oral ITZ group. In a cat with a single lesion, topical treatment alone (HGN-ITZ) provided complete healing of the lesion in 45 days. No signs of topical irritation were observed during the treatments, suggesting that HGN-ITZ can be a promising strategy in the treatment of sporotrichosis.

Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.

Coelomycetous fungi are among the emerging causes of infections and have been involved in many kinds of infections, including keratitis and endophtalmitis. Here, we present the first case of keratitis caused by Neocucurbitaria unguis-hominis, a coelomycetous fungus belonging to the family Cucurbitariaceae. In this case report, we describe the clinical presentation of a 56-year-old woman, a regular contact lens wearer, who was treated for pain in her right eye and fixed spot vision after an injury with plant debris. On examination, a corneal ulcer was observed, the foreign body was removed, and topical eye-drop therapy was started. After an initial improvement, the patient returned three weeks later due to a recurrence of discomfort in her right eye, observing the persistence of the corneal ulcer. Corneal scrapings were taken for culture, growing a filamentous fungus after seven days, which was identified by sequencing the fungal internal transcribed spacer region. It should be noted that microbiological identification of the coelomycetes in the clinical laboratory is not easy because of their difficulty in sporulating, making molecular techniques based on the amplification and sequencing of appropriate phylogenetic markers essential. Identification of these fungi is mandatory in order to optimise treatment due to the difficulty in eradicating them with antifungal treatment, requiring surgery in 50% of cases.

Species of the Candida genus represent the third most common cause of onychomycosis, the most frequent and difficult to treat nail infection. Onychomycosis has been attributed to fungi organized in biofilm and some natural products have proved promising for its treatment. This study aimed to evaluate the antibiofilm activity of propolis extract (PE) and its by-product (WPE) on 7-day preformed biofilms produced by Candida albicans in polystyrene microplates, as well as in an ex vivo model on human nail fragments. The cytotoxicity and permeation capacity were also assessed. Firstly, multiple parameters were evaluated over 7 days to elucidate the dynamics of biofilm formation by C. albicans. The cell viability and total biomass did not vary much from the beginning; however, days 3 and 4 were crucial in terms of metabolic activity, which was significantly increased, and the levels of extracellular matrix components, wherein proteins and nucleic acids experienced an increase, but polysaccharide levels dropped. Architecturally, one-day biofilm showed a monolayer of organized cells (blastoconidia, hyphae, and pseudohyphae), while in the seven-day biofilm there was a three-dimensional well-structured and complex biofilm. This yeast was also able to form a biofilm on both surfaces of the nail, without an additional nutritional source. Both extracts showed excellent antibiofilm activity against the 7-day preformed biofilm and were not toxic to Vero cells at concentrations compatible with the antifungal and antibiofilm activities. Both extracts permeated the experimentally infected nail, with WPE being more efficient. The results of this study, taken together, reinforce the potential of these natural products, containing propolis, as a safe option for the topical treatment of onychomycosis.

A female patient in her 20s presented with a bulbar conjunctival mass lesion that was diagnosed as nodular scleritis. It was treated with topical and oral steroids in another hospital. Imaging was done using anterior segment optical coherence tomography and ultrasound biomicroscopy, which helped to rule out scleritis and subconjunctival cysticercosis. Histopathology of the excision biopsy specimen revealed fungal filaments. Topical antifungals were started, and the condition resolved without recurrence after therapy. Although rare, infections should be considered in the differential diagnosis of conjunctival mass lesions. Imaging can help to rule out other entities and guide towards appropriate management.

Fluconazole (FLZ) is the most widely used antifungal agent for treating cutaneous candidiasis. Although oral FLZ has been proved to be effective, the incidence of side effects necessitates the development of an effective formulation that could surpass the pitfalls associated with systemic availability. Accordingly, this research aimed at developing a self-assembled mixed micelles topical delivery system to enhance the topical delivery of the drug. Self-assembled mixed micelles were developed using D-α-tocopheryl polyethylene glycol 1000 succinate and phospholipids and optimized using Box-Behnken design. The optimized formulation with minimized size was then tested in vivo for the antifungal activity against C. albicans in immunocompromised mice. Treatment with the optimized formulation led to decreased peripheral erythema as well as lesions due to fungal infection in comparison to raw FLZ loaded gel. Therefore, the developed formulation was found to be a promising vehicle for the treatment of cutaneous candidiasis.

We report a case of intractable Aspergillus otomycosis with multiple relapses despite conventional topical and systemic antifungal treatment, and adjunctive usage of hyperbaric oxygen therapy. Of note, otomycosis relapsed even after six months of continuous systemic antifungal treatment with therapeutic drug levels and without treatment interruption; and only resolved after application of topical voriconazole. (max. 75 words).

Lavender is a valuable medicinal plant belonging to the Lamiaceae family. Currently 39 species are known, but only Lavandula angustifolia is a pharmacopoeial raw material. Lavender has a long history of medicinal use and mainly exhibits antioxidant, anti-inflammatory, sedative, antidepressant, spasmolytic, anticholinesterases, antifungal and antibacterial properties. Used internally, it relieves symptoms of mental stress and insomnia and supports digestion. Topical use of lavender in aromatherapy, neuralgia and antiseptics is also known. The constant interest in lavender, and in particular in Lavandula angustifolia, in the field of medicine and pharmacy is evidenced by the growing number of publications. In view of so many studies, it seems important to review traditional and modern extraction techniques that determine the chemical composition responsible for the antioxidant and anti-inflammatory effects of various extracts from the species of the Lavandula genus.

The occurrence of candidiasis, including superficial infections, has recently increased dramatically, especially in immunocompromised patients. Their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. The aim of this study was to determine the antifungal effect of clove essential oil (CEO) and eugenol (EUG) towards both reference and clinical Candida spp. strains isolated from the oral cavity of patients with hematological malignancies, and to investigate their mode of action and the interactions in combination with the selected antimycotics. These studies were performed using the broth microdilution method, tests with sorbitol and ergosterol, and a checkerboard technique, respectively. The CEO and EUG showed activity against all Candida strains with a minimal inhibitory concentration (MIC) in the range of 0.25-2 mg/mL. It was also found that both natural products bind to ergosterol in the yeast cell membrane. Moreover, the interactions between CEO and EUG with several antimycotics-cetylpyridinium chloride, chlorhexidine, silver nitrate and triclosan-showed synergistic or additive effects in combination, except nystatin. This study confirms that the studied compounds appear to be a very promising group of phytopharmaceuticals used topically in the treatment of superficial candidiasis. However, this requires further studies in vivo.

The indications for nystatin as prophylaxis or treatment are limited. In the PASOAP (Pediatric Antifungal Stewardship Optimizing Antifungal Prescription) study, high use of nystatin in hospitalized children beyond the neonatal age was observed. In this report, we present the data on nystatin use in infants and children ≥ 3 months who participated in the PASOAP study. Nystatin was prescribed mainly for prophylaxis. Congenital heart disease, cystic fibrosis, and chronic renal disease were the most commonly reported conditions in children receiving prophylactic nystatin. There is sparse evidence supporting the use of nystatin prophylaxis beyond neonates; trials in specific pediatric patient groups are required.

Fungal skin infection is a major skin health issue worldwide. For the treatment of fungal infections, systematic antifungal therapies are frequently prescribed. The aim of this study is to prepare an antifungal cold cream from Caralluma adscendens var. attenuata to treat deep dermal fungal infection in the skin layer. To achieve this, different concentrations of plant extract-based cold cream were prepared, and their in vitro characteristic features such as color, texture, pH, viscosity, spreadability, stability, permeation, were analyzed together with ex vivo evaluation to identify their applicability in the treatment of acute rat skin irritation. After 72 h of induction of Candida albicans infection in rats (7 days, two times/day), C. adscendens var. attenuata cold cream was applied topically. In rats with C. albicans induction without any treatment, adverse skin damages were visible in the form of red rashes, whereas in those with the formulated cold cream application, significantly less skin damage and inflammation were observed on a dose-dependent basis. Moreover, the reduced microbial colonization and histopathology of the rat skin without any treatment indicated the successful invasion of C. albicans and showed the morphological changes caused by candidal infection. However, treatment with the C. adscendens var. attenuata cream significantly inhibited candida colonization and reversed the morphological changes. In addition, the formulated C. adscendens var. attenuata cold cream showed good spreadability, permeation, and viscosity. Hence, it can act as a potent antifungal topical agent for the treatment of C. albicans skin infection without any irritation, thus safeguarding the skin tissue.

Autosomal dominant hyper-IgE syndrome (AD-HIES) caused by dominant negative (DN) variants in the signal transducer and activator of transcription 3 gene (STAT3) is characterized by recurrent Staphylococcal abscesses, severe eczema, chronic mucocutaneous candidiasis (CMC), and non-immunological facial and skeletal features.

The recent monsoon rains in Pakistan were unprecedented and caused flooding all over Pakistan, especially in Sindh and Balochistan. Following this national disaster, various water-borne and contagious diseases started erupting all over the country. In such a calamity-struck city of Jacobabad, we started receiving cases with a peculiar set of ocular complaints mimicking viral keratoconjunctivitis. Failure to respond to traditional treatment and the unique appearance of these corneal opacities led to a rare diagnosis of Microsporidial Keratoconjunctivitis, which was later confirmed by microscopy and staining of corneal scrapings of the most affected case. In line with published literature, all cases were treated with topical fluoroquinolone and topical anti-fungal therapy, following which the disease was cleared within a week. The disease has seen an upward trend the world over, especially among Asia. To the best of our knowledge, no such cases have been reported in Pakistan as yet. In this case series, we highlight the strong correlation of emergence of microsporidial keratitis in patients following exposure to pooled water bodies after the monsoon rainy season and floods. Moreover, this report will help create awareness in eye professionals regarding the prevention, timely diagnosis and treatment of these rare and emerging cases. Key Words: Keratitis, Spores, Water-borne diseases, Microsporidia.

Malassezia pachydermatis is a commensal of canines associated with Malassezia dermatitis. Consensus guidelines recommend topical and/or systemic treatment, but resistance to antifungals has been reported. The objective of this pilot study was to determine the efficacy of a 0.003% colloidal silver nanoparticle-based shampoo in the treatment of canine Malassezia dermatitis. Dogs were included based on compatible history, presentation, and at least one positive cytology. Fourteen privately owned dogs were bathed every 48 hr for up to 28 days, allowing 5-10 min of contact time. The mean Malassezia organisms for 10 oil immersion fields at each Malassezia dermatitis-affected body area was recorded at days 0 and 14. Dogs positive on day 14 had cytologies performed on day 28. Eleven dogs (78.6%) were cytologically negative by day 28. Nine (81.8%) of these were negative by day 14. One dog (7.14%) had partial resolution (negative in 3/4 Malassezia dermatitis areas) by day 28. These results suggest that silver nanoparticle-based shampoo may be effective in the treatment of canine Malassezia dermatitis. Larger, controlled studies are needed to further investigate efficacy, optimal concentration, and ideal application frequency.

Imidazole (IM) and salicylic acid (SA) have a significant class among the medical compound. These are widely used as topical drugs like antifungal, antibacterial, anticancer, immunosuppressive agent, etc. These two bioactive organic moieties are combined by a weak hydrogen bond formed by hydrogen transfer. The charge transfer (CT) complex of acceptor (SA) and donor (IM), has been synthesized at room temperature in methanol and confirmed by signal-crystal XRD, conductance and UV-visible spectroscopy. The X-ray crystallography provides the original structural information of CT complex and displays the existence of N+-H--O- bond between IM and SA. The physical properties such as (ECT), (RN), (ID), (f), (D) and (Δ G0) along with molar extinction coefficient (εCT) and formation constant (KCT) were estimated through UV-visible spectroscopy. Job's method and Benesi-Hildebrand equation suggested 1:1 stoichiometry of ([IM]+[SA]-). The results indicate a complete transfer of hydrogen atom and CT complex formation with 1:1 molar ratio of IM and SA. Antimicrobial activity was veiled against different bacteria like Escherichia coli, Bacillus subtilis and Staphylococcus aureus; and different fungi as Fusarium oxysporum, Candida albicans and Aspergillus niger by disc diffusion method. CT complex was also tested for cytotoxic activity against lung cancer cell lines in comparison to breast cancer cell lines. Molecular docking provides the information of binding of [(IM)+(SA)-] with the cancer marker (1M17), which has substantial application for drug designing. The investigational studies were supplemented through time-dependent density functional theory (TD-DFT) using basis set B3LYP/6-311G**. Through DFT calculations, HOMO→LUMO electronic energy gap (ΔE) was obtained.

Phaeohyphomycosis caused by Exophiala species represents an important disease of concern for farmed and aquarium-housed fish. The objective of this study was to summarize the clinical findings and diagnosis of Exophiala infections in aquarium-housed Cyclopterus lumpus. Clinical records and postmortem pathology reports were reviewed for 15 individuals from 5 public aquaria in the United States and Canada from 2007 to 2015. Fish most commonly presented with cutaneous ulcers and progressive clinical decline despite topical or systemic antifungal therapy. Antemortem fungal culture of cutaneous lesions resulted in colonial growth for 7/12 samples from 8 individuals. Amplification of the internal transcribed spacer region (ITS) of nuclear rDNA identified Exophiala angulospora or Exophiala aquamarina in four samples from three individuals. Postmortem histopathologic findings were consistent with phaeohyphomycosis, with lesions most commonly found in the integument (11/15), gill (9/15), or kidney (9/15) and evidence of fungal angioinvasion and dissemination. DNA extraction and subsequent ITS sequencing from formalin-fixed paraffin-embedded tissues of seven individuals identified E. angulospora, E. aquamarina, or Cyphellophora sp. in four individuals. Lesion description, distribution, and Exophiala spp. identifications were similar to those reported in farmed C. lumpus. Antemortem clinical and diagnostic findings of phaeohyphomycosis attributable to several species of Exophiala provide insight on the progression of Exophiala infections in lumpfish that may contribute to management of the species in public aquaria and under culture conditions.

Seborrheic dermatitis (SD) is a common skin disease with signs and symptoms that may vary by skin color, associated medical conditions, environmental factors, and vehicle preference. Diagnosis of SD is based on presence of flaky, "greasy" patches, and/or thin plaques accompanied by erythema of the scalp, face, ears, chest, and groin and is associated with pruritus in many patients. The presentation may vary in different skin types and hyper- or hypopigmentation may occur, with or without erythema and minimal or no scaling. While the pathogenesis is not certain, 3 key factors generally agreed upon include lipid secretion by sebaceous glands, Malassezia spp. colonization, and some form of immunologic dysregulation that predisposes the patient to SD. Treatment involves reducing proliferation of, and inflammatory response to, Malassezia spp. Topical therapies, including antifungal agents and low potency corticosteroids, are the mainstay of treatment but may be limited by efficacy and side effects. Few novel treatments for SD are currently being studied; however, clinical trials assessing the use of topical phosphodiesterase-4 inhibitors have been completed. Improving outcomes in SD requires recognizing patient-specific manifestations/locations of the disease, including increased awareness of how it affects people of all skin types.

Herein, we report a case of otitis externa caused by Malassezia slooffiae complicated with mastoiditis. A 70-year-old male complained of fever and severe otorrhea from left external auditory canal 2 months after undergoing a craniotomy to remove a hematoma. He had right-sided paralysis and undertook bed rest. Brain computed tomography revealed continuous fluid accumulation in the left mastoid air cells and middle ear from left external auditory canal in addition to leukocytosis and increased C-reactive protein level. The tympanic membrane was severely swelling. These results indicated the presence of otitis media and mastoiditis. Otorrhea culture showed large amounts of M. slooffiae. The administration of liposomal amphotericin B (L-AMB), the irrigation of external auditory canal with normal saline, and the application of topical ketoconazole ointment were started. The administration of L-AMB for 8 weeks and voriconazole, which was switched from L-AMB, for 4 weeks ameliorated his infection and he was transferred to another hospital to receive rehabilitation. From these results and his clinical course, the diagnosis of otitis externa caused by Malassezia slooffiae complicated with mastoiditis was made. And the possibility of the contamination by M. slooffiae was very low. Clinicians should be aware that M.slooffiae can provoke otological infections since M. slooffiae is the most common Malassezia sp. in external auditory canal.