Sporotrichosis caused by Sporothrix brasiliensis is an emergent mycosis that is now a worldwide concern. One important step to sporotrichosis control is its correct treatment. However, limitations abound; thus, new antifungals, mainly focused on S. brasiliensis, are urgently needed. We performed a systematic review (following the PRISMA guideline) focused on (1) the global distribution of human and animal sporotrichosis by S. brasiliensis, especially outside of Brazil; (2) appraising therapies tested against this pathogen. We identified sporotrichosis caused by S. brasiliensis reported in five countries (Paraguay, Chile, Argentina, the United Kingdom, and the United States) in addition to Brazil, occurring on three continents, highlighting the epidemiological scenario in Argentina with an important increase in reported cases in recent years. Regarding the antifungal activity of drugs, 25 articles described the in vitro action of 20 unique chemicals and eight repurposed drugs against S. brasiliensis. Only five studies reported in vivo activity against S. brasiliensis (five drugs) using invertebrate and vertebrate models. Sporotrichosis caused by S. brasiliensis has a global impact and it is no longer specifically a Brazilian problem. We review the need for understanding the disease epidemiology, education of clinicians and of the populace, organization of health care delivery to respond to a spreading epidemic, and research on therapy for sporotrichosis.

Background. Natural host defence molecules, part of innate immunity and the first line of defence, are evolutionarily conserved. Some pharmaceutical properties undesirable for clinical use led to the rational design of synthetic molecules with constructed peptide arrangements, giving a novel therapeutic avenue. A prior publication showed synthetic peptide RP557 inhibition and killing of fluconazole-sensitive and resistant Candida species isolates, biofilm inhibition, no resistance induction, direct membrane action, negligible mammalian cell toxicity and topical efficacy in a rodent vaginal candidiasis model. These findings highlight the relevance of investigating RP557 activity against other fungal pathogens. Objective. We evaluated the antifungal spectrum of the RP557 against World Health Organization-listed priority fungal pathogens, including endemic and skin fungal pathogens, both alone and in combination with commercial antifungal drugs. Methods. The antifungal spectrum was evaluated by broth dilution vs. clinical isolates, and we present 76 MICs (mcg ml ⁻¹ ) performed according to M27 or M38 CLSI documents, 35 checkerboard interactions with antifungals and 10 minimum fungicidal determinations. Results. Overall impression is robust activity vs. chromoblastomycosis and mycetoma species, Cryptococcus neoformans and Trichophyton spp.; broad MIC ranges within most species, least activity vs. Mucorales and Aspergillus spp.; and some promising drug interactions vs. Sporothrix spp. and Candida auris . Conclusion. Additional efficacy data in vivo is needed. Topical therapy could give local concentrations exceeding MICs, and burn or trauma prophylaxis or treatments are attractive potential targets owing to RP557 panmicrobial properties.

Background/Objectives: Dermatophytosis is among the most prevalent fungal infections worldwide, and the emergence of antifungal resistance highlights the need for novel the-rapeutic strategies. Organoselenium compounds have demonstrated promising antifungal activity against several pathogenic fungi, although their activity against dermatophytes remains poorly explored. Here we investigate the in vitro antifungal activity of four organoselenium compounds, ebselen, diphenyl diselenide [(PhSe)₂], p-methoxy-diphenyl diselenide (BMD), and bis-(3-trifluoromethyl phenyl) diselenide (CF₃). Methods: Eighteen clinical isolates belonging to the T. mentagrophytes (n = 10) and T. rubrum (n = 8) species complexes were studied and potential synergism with fluconazole (FCZ) also explored. Antifungal susceptibility testing and drug interaction were performed according to Clinical and Laboratory Standards Institute broth microdilution protocols and checkerboard assay, respectively. Results: Ebselen, (PhSe)₂, and BMD inhibited all Trichophyton spp. isolates with a geometric mean (GM) of minimum inhibitory concentration (MIC) less than or equal to 6 µg/mL. CF₃ inhibited 78% (14/18) of the isolates and had higher MICs (GM ≥ 43.5 µg/mL). Combination assays revealed synergistic interactions between FCZ and the organoselenium compounds, ranging from 45% to 89%, without antagonistic interactions. Moreover, FCZ activity was enhanced in 57–86% of resistant isolates, with BMD showing the most favorable profile in combination with FCZ. Conclusions: These findings demonstrate the promising antifungal potential of organoselenium compounds against the major dermatophytes associated with human infection and support further investigation of these compounds, particularly ebselen, (PhSe)₂, and BMD, as novel antifungal agents, either alone or in combination with conventional antifungal drugs.

Background: Sporothrix brasiliensis-associated sporotrichosis is an emerging zoonotic mycosis in South America, especially in Brazil. Whereas sporotrichosis is classically described as a lymphangitic disease, multifocal forms occur, predominantly in people living with HIV (PLHIV). We report two cases of severe multifocal cutaneous sporotrichosis caused by S. brasiliensis in PLHIV from a hyperendemic region in southern Rio Grande do Sul, Brazil, and review the relevant literature. Methods and Results: Both patients presented advanced immunosuppression, low CD4+ T-cell counts, and poor adherence to antiretroviral therapy, which contributed to disease progression. The first patient developed recurrent multifocal lesions over a two-year period, whereas the second progressed from extensive mucocutaneous involvement to multifocal disease with partial destruction of nasal cartilage, resulting in permanent sequelae. In both cases, S. brasiliensis was confirmed by culture and species-specific polymerase chain reaction. Isolates from both cases exhibited wild-type susceptibility to itraconazole. Treatment with itraconazole was given, with no susceptibility changes in sequential isolates recovered during disease progression nor after antifungal therapy abandonment. Conclusion: These cases highlight that extensive tissue destruction and permanent deformities, resembling that from other systemic mycoses, can occur in PLHIV. Our findings and review reinforces the importance of early HIV investigation, adherence to antiretroviral and antifungal therapies, and continuous epidemiological and antifungal susceptibility surveillance in hyperendemic regions.

Sporotrichosis is a neglected fungal disease, affecting mammals. Here, a feline patient presented a small ulcerated lesion. Short treatment by itraconazole resulted in clinical cure. The isolate was identified as Sporothrix brunneoviolacea by sequencing. Despite proper growth, antifungal susceptibility testing by microbroth dilution could not be performed due to a lack of growth. This is the first report of sporotrichosis by S. brunneoviolacea, which was originally classified as an environmental and non-pathogenic species.