Onychomycosis is a chronic fungal infection of nails, commonly caused by dermatophyte fungi, primarily species of Trichophyton. Because of the limited drug arsenal available to treat general fungal infections and the frequent failure of onychomycosis treatment, the search for new therapeutic sources is essential, and topical treatment with natural products for onychomycosis has been encouraged. Propolis, an adhesive resinous compound produced by honeybees (Apis mellifera), has shown multiple biological properties including significant antifungal and anti-biofilm activities in vitro. In spite of promising in vitro results, in vivo results have not been reported so far. This study assessed an ethanol propolis extract (PE) as a topical therapeutic option for onychomycosis, including its characterization in vitro and its applicability as a treatment for onychomycosis (from bench to clinic). The in vitro evaluation included analysis of the cytotoxicity and the antifungal activity against the planktonic cells and biofilm formed by Trichophyton spp. We also evaluated the capacity of PE to penetrate human nails. Patients with onychomycosis received topical PE treatments, with a 6-month follow-up period. The results of the in vitro assays showed that PE was non-toxic to the cell lines tested, and efficient against both the planktonic cells and the biofilm formed by Trichophyton spp. The results also showed that PE is able to penetrate the human nail. The results for PE applied topically to treat onychomycosis were promising, with complete mycological and clinical cure of onychomycosis in 56.25% of the patients. PE is an inexpensive commercially available option, easy to obtain and monitor. Our results indicated that PE is a promising natural compound for onychomycosis treatment, due to its ability to penetrate the nail without cytotoxicity, and its good antifungal performance against species such as Trichophyton spp. that are resistant to conventional antifungals, both in vitro and in patients.

Aim. To evaluate the topical treatment of onychomycosis using a 10% hydroalcoholic propolis extract (PE) in two aleatorily chosen patients and analyze possible risk factors from hosts including some particularities of the isolated fungi that may justify the outcomes achieved. Materials and Methods. A topical treatment, with PE, was started in two cases of toe onychomycosis due to T. rubrum. The in vitro PE antifungal activity against these isolates was confirmed. Moreover, the ability of the fungi to infect the human nail was evaluated also in an ex vivo study, analyzed by histopathology. Results. Within four months, both patients showed evident improvement, but with different outcomes. The possible host-related risk factors justifying the poorer outcome in patient 1 include a longer duration time of onychomycosis (50 years). Some particularities in the T. rubrum strain isolated from this patient in relation to that found in patient 2 were observed: (1) the hypha morphology suggesting a major adaptation of the fungus to the host; (2) a 16 times greater propolis concentration was required in vitro; and (3) a faster ability to start a growth using the nail as the only nutritional source. Additionally, this isolate was more efficient in producing a biofilm on the nail surface. Conclusions. A partial clinical and complete mycological cure for the two patients was achieved after four months of PE daily use. Despite a complete recovery, a different outcome was observed between both cases. A more persistent onychomycosis, added to greater fungal potential to produce biofilm on the nail, seems to influence greatly the success of a topical treatment with PE.

26Background: Traditionally known as a common contaminant, Rhodotorula mucilaginosa is 27 among the leading causes of invasive fungal infections by non-candida yeasts. They affect 28 mainly immunocompromised individuals, often mimicking the cryptococcosis infection, 29 despite invasive infections by Rhodotorula are still not well explained. Thus, here we aimed to 30 characterize microbiologically clinical isolates of R. mucilaginosa isolated from colonization 31 of a patient with chronic renal disease (CKD), as well as to evaluate their phylogeny, antifungal 32 susceptibility, virulence, and pathogenicity in order to infer the potential to become a possible 33 infection. 34 Methodology/Principal Findings: For this study, two isolates of R. mucilaginosa from oral 35 colonization of a CKD patient were isolated, identified and characterized by classical 36 (genotypic and phenotypic) methods. Susceptibility to conventional antifungals was evaluated, 37 followed by biofilm production, measured by different techniques (total biomass, metabolic 38 activity, colony forming units and extracellular matrix quantification). Finally, the 39 pathogenicity of yeast was evaluated by infection of Tenebrio molitor larvae. 40All isolates were resistant to azole and sensitive to polyenes and they were able to adhere and 41 form biofilm on the abiotic surface of polystyrene. In general, similar profiles among isolates 42 were observed over the observed periods (2, 24, 48 and 72 hours). Regarding extracellular 43 matrix components of biofilms at different maturation ages, R. mucilaginosa was able to 44 produce eDNA, eRNA, proteins, and polysaccharides that varied according to time and the 45 strain. The death curve in vivo model showed a large reduction in the survival percentage of 46 the larvae was observed in the first 24 hours, with only 40% survival at the end of the 47 Conclusions/Significance: We infer that colonization of chronic renal patients by R. 49 mucilaginosa offers a high risk of serious infection. And also emphasize that the correct 50 identification of yeast is the main means for an efficient treatment. 51 52 53 3 Author Summary 54The genus Rhodotorula is known to be a common contaminant, however, it has been 55 increasing in the last years, reports of different forms infections by this yeast, reaching mainly 56 individuals with secondary diseases or with low immunity. However, very little is known about 57 the mechanism that triggers the disease. Thus, this study aims to characterize microbiologically 58 clinical isolates of R. mucilaginosa isolated from a patient with chronic renal disease, as well 59 as to evaluate their phylogeny, antifungal susceptibility, virulence, and pathogenicity in order 60 to infer the potential to become a possible infection. It was possible to characterize in general 61 the clinical isolates, to determine that they are resistant to an important class of the antifungal 62 agents which are the azoles. In addition, they are able to adhere and to form biofilm on abiotic 63 surfaces, t...

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ObjectiveTo analyse the records of male hospitalisation for fungal infections, including their spatial distribution and the main invasive epidemiological and sociodemographic characteristics in the State of Paraná, Brazil.MethodsSpatial analysis based on data from male admission records for invasive fungal infections (IFIs) in the State of Paraná, from 2015 to 2019. Data were taken from the hospital records obtained in the Hospital Information System of the Unified Health System, being collected, georeferenced and analysed to infer the existence of autocorrelation with the hospitalisation rates in the state.ResultsFrom 2015 to 2019, there were 385 cases of IFIs in men, being more prevalent in white individuals aged 61–70 years. We observed that the metropolitan, southeast, central‐eastern, north‐central, northwestern and western regions formed high–high clusters, with regions with a high number of registered cases. In the regression, there was an association with socioeconomic and demographic factors that showed a correlation with the rates of hospitalisation for IFIs.ConclusionThe study draws attention to Paraná as an endemic region for paracoccidioidomycosis, in addition to presenting high rates of nosocomial fungal infections. We also emphasise the importance of compulsory notification in the state and in the country to gain greater control over the incidence and prevalence of cases and to incentivise the creation of public policies for the prevention of IFIs.