In vitro isavuconazole activity against Sporothrix brasiliensis suggests its efficacy in some severe sporotrichosis cases.

Background: Sporothrix brasiliensis causes sporotrichosis, an important infection in some groups of patients. Aims: This work was designed to investigate the effects of isavuconazole against this species. Methods: An antifungal susceptibility test was performed to compare MIC values with other antifungal drugs used to treat sporotrichosis. A checkerboard assay was performed to understand isavuconazole interactions. Furthermore, isavuconazole growth inhibition on an itraconazole-resistant strain was tested. Results: Isavuconazole had similar MICs to other azoles against S. brasiliensis, presenting fungistatic activity. Isavuconazole did not interact in vitro with antifungals or immunosuppressive drugs and inhibited the growth of an itraconazole-resistant strain. Conclusion: Isavuconazole inhibits S. brasiliensis, its pharmacologic characteristics make it a candidate for patients with sporotrichosis and it may be useful to combat sporotrichosis caused by resistant isolates.

Isavuconazole is a drug that remains largely unstudied, especially for fungal infections that develop at the site of a break in the skin, such as a wound. The authors conducted experiments in order to study and evaluate isavuconazole's effects on sporotrichosis; in particular whether the drug could stop or kill these fungi. The results show that isavuconazole is highly effective against Sporothrix brasiliensis, the main species that causes sporotrichosis in Brazil and other countries in South America, by inhibiting the fungal growth. Isavuconazole was also effective for different strains that were not inhibited by other drugs. This is important because, in the future, it could improve the treatment of sporotrichosis.

SARS-CoV-2 Post-Infection and Sepsis by Saccharomyces cerevisiae: A Fatal Case Report-Focus on Fungal Susceptibility and Potential Virulence Attributes.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for approximately 6.8 million deaths worldwide, threatening more than 753 million individuals. People with severe coronavirus disease-2019 (COVID-19) infection often exhibit an immunosuppression condition, resulting in greater chances of developing co-infections with bacteria and fungi, including opportunistic yeasts belonging to the Saccharomyces and Candida genera. In the present work, we have reported the case of a 75-year-old woman admitted at a Brazilian university hospital with an arterial ulcer in the left foot, which was being prepared for surgical amputation. The patient presented other underlying diseases and presented positive tests for COVID-19 prior to hospitalization. She received antimicrobial treatment, but her general condition worsened quickly, leading to death by septic shock after 4 days of hospitalization. Blood samples collected on the day she died were positive for yeast-like organisms, which were later identified as Saccharomyces cerevisiae by both biochemical and molecular methods. The fungal strain exhibited low minimal inhibitory concentration values for the antifungal agents tested (amphotericin B, 5-flucytosine, caspofungin, fluconazole and voriconazole), and it was able to produce important virulence factors, such as extracellular bioactive molecules (e.g., aspartic peptidase, phospholipase, esterase, phytase, catalase, hemolysin and siderophore) and biofilm. Despite the activity against planktonic cells, the antifungals were not able to impact the mature biofilm parameters (biomass and viability). Additionally, the S. cerevisiae strain caused the death of Tenebrio molitor larvae, depending on the fungal inoculum, and larvae immunosuppression with corticosteroids increased the larvae mortality rate. In conclusion, the present study highlighted the emergence of S. cerevisiae as an opportunistic fungal pathogen in immunosuppressed patients presenting several severe comorbidities, including COVID-19 infection.

Single nucleotide polymorphisms and chromosomal copy number variation may impact the Sporothrix brasiliensis antifungal susceptibility and sporotrichosis clinical outcomes.

Feline-transmitted sporotrichosis has garnered attention due to the recent high incidence and the lack of efficient control in the epicenter of the epidemic, Rio de Janeiro, Brazil. Sporothrix brasiliensis is the major pathogen involved in feline-to-human sporotrichosis in Brazil and displays more virulent genotypes than the closely related species S. schenckii. Over the last two decades, several reports of antifungal-resistant strains have emerged. Sequencing and comparison analysis of the outbreak strains allowed us to observe that the azole non-wild-type S. brasiliensis strain CFP 1054 had significant chromosomal variations compared to wild-type strains. One of these variants includes a region of 231 Kb containing 75 duplicated genes, which were overrepresented for lipid and isoprenoid metabolism. We also identified an additional strain (CFP 1055) that was resistant to itraconazole and amphotericin B, which had a single nucleotide polymorphism in the tac1 gene. The patients infected with these two strains showed protracted clinical course and sequelae. Even though our sample size is modest, these results suggest the possibility of identifying specific point mutations and large chromosomal duplications potentially associated with antifungal resistance and clinical outcomes of sporotrichosis.

Performance of mycology and histopathology tests for the diagnosis of toenail onychomycosis due to filamentous fungi: Dermatophyte and non-dermatophyte moulds.

Improvement of laboratory diagnosis of onychomychosis is important so that adequate treatment can be safely implemented. To evaluate and compare the performance of mycological and histopathological examinations in onychomycoses caused by dermatophyte and non-dermatophyte moulds. Patients with lateral/distal subungual onychomycosis in at least one hallux were enrolled in the protocol and assessed via mycological and histopathological tests. The isolation of filamentous fungi was considered the gold standard. Test performance was evaluated through sensitivity, specificity and positive and negative predictive values. A total of 212 patients were enrolled in the study. Direct microscopy (DM) was positive in 57.5% patients, and cultures in 34.4%. Among these patients, 23.3% were positive for dermatophytes, with Trichophyton rubrum the most frequently isolated, and 86.3% were positive for non-dermatophytes, with Neoscytalidium dimidiatum predominance. Histopathology was positive in 41.0% samples. Direct microscopy showed better sensitivity for non-dermatophyte moulds (P=.000) and nail clipping was more specific for dermatophyte (P=.018). Histopathology of the distal nail plate is a valuable complementary tool for the diagnosis of onychomycosis caused by dermatophytes and direct microscopy is especially useful for non-dermatophyte molds.

Cutaneous murine model of infection caused by Neoscytalidium dimidiatum: a preliminary study of an emerging human pathogen.

Neoscytalidium dimidiatum is an emerging fungus that causes a skin infection similar to dermatophytosis; it affects both immunocompetent and immunosuppressed individuals, and it may invade deeper tissues and organs and cause systemic disease. Little is known about the etiopathogenesis of the infection caused by this fungus, and no standard effective treatment is available. The aim of the present experimental study was to develop an animal model of skin infection with N. dimidiatum. BALB/c mice were inoculated with two fungal strains, and different routes of infection were tested. When challenged intradermally, N. dimidiatum strain HUPE164165 caused skin infection in 67% of the animals whereas strain HUPE115669 did it in 49%. Neoscytalidium dimidiatum was isolated from the skin of 25% of the animals inoculated via epidermal scarification and from 100% of the animals challenged via subcutaneous injection. Mice inoculated intradermally were followed-up during four weeks, and clinical samples were collected on days 3, 8, 15, and 29 after inoculation, corresponding to different stages of infection. The cutaneous infection rate, as measured by the recovery of N. dimidiatum strain HUPE164165 from skin biopsies of animals inoculated intradermally, revealed the presence of infection in 90% of the animals sacrificed at 3 days post-inoculation, 71% at 8, 85% at 15, and 33% at 29. Conidia and hyphae were observed in PAS-stained sections as well as a mild to moderate inflammatory infiltrate in haematoxylin-eosin, although it did not differ from animals inoculated either with T. quinckeanum or PBS. The intradermal route of inoculation was considered to be suitable for the study of skin infection with N. dimidiatum The animal model developed in this preliminary study is the first to allow the study of cutaneous infection with N. dimidiatum and may contribute to further investigations of the aetiology, immunology, pathogenesis and treatment targeting this emerging mycosis.

Intermittent therapy with terbinafine and nail abrasion for dermatophyte toe onychomycosis: a pilot study.

Onychomycosis constitutes up to 50% of all nail disorders. Toenails are generally affected, mostly due to dermatophytes. Terbinafine is the most potent antifungal agent in vitro against dermatophytes. There are few randomised controlled trials using a non-continuous dose of terbinafine. The aim of this open-label pilot study was to reduce the total drug amount, the collateral effects and, specially, the costs; albeit maintaining the same efficacy of the standard regimens. Compare the outcomes of two different intermittent regimens with the same total amount of the medication (42 tablets in 6 months). Forty-one patients were divided into the following groups: terbinafine 250 mg day(-1) , for 7 days, monthly or terbinafine 500 mg day(-1) , once daily, for 7 days, every 2 months, both plus nail abrasion during 6 months. The efficacy was evaluated at months 6, 12 and 18 using the disease free nail criteria. Total cure = group I: eight patients (44.4%) and group II: eight patients (44.4%). Partial cure = group I: five patients (27.8%) and group II: four patients (22.2%). Treatment failure = group I: five patients (27.8%) and group II: three patients (16.7%). Recurrence = group I: zero patients (0.0%) and group II: three patients (16.7%). Two intermittent dosing regimens of terbinafine plus nail abrasion proved to be an alternative statistically effective, safe and with reduced drug costs for dermatophytes toenail onychomycosis.

Onychomycosis due to Neoscytalidium treated with oral terbinafine, ciclopirox nail lacquer and nail abrasion: a pilot study of 25 patients.

BACKGROUND: Onychomycosis by Neoscytalidium constitutes chronic infection of the nails, and its frequency has increased in recent decades. Currently, no effective standard treatment exists and literature data remain scarce. This work aimed to conduct a pilot project of combined treatment for this infection. METHODS: Thirty patients were divided into three treatment groups: oral terbinafine plus ciclopirox nail lacquer twice a week; ciclopirox nail lacquer twice a week; and ciclopirox nail lacquer 5 days a week, all associated with nail abrasion when required, for 12 months, with 6 months posttreatment follow-up. Clinical and mycological criteria were used for evaluation. RESULTS: Twenty-five patients completed the study. Significant clinical lesion reduction in disease occurred in all three treatment groups: 21 patients (84%) entered the study with more than 50% of diseased nail plate, at the end of treatment, and at 6-month follow-up, 84 and 96%, respectively, presented less than 25% nail lesion. Negative microscopy was observed in 36% of the patients at the end of treatment and in 24% of the patients at 6-month follow-up. At treatment completion (12 months), culture was negative in 21 patients (84%) and in 18 (72%) at follow-up. It was not possible to establish any clinical or mycological statistical differences between groups (p > 0.05). Global medical evaluation upon treatment completion revealed that one patient (4%) presented complete cure, 8 (32%) presented partial cure, 16 (64%) presented therapeutic failure. At the end of follow-up period, 6 patients (24%) were considered to have recurrence/reinfection. CONCLUSIONS: The results obtained at the 6-month period of follow-up showed marked improvement (96% of clinical improvement and 72% of negative culture) of the patients treated for onychomycosis caused by Neoscytalidium in the three tested groups with no statistical differences between them. Multicentric studies with greater number of patients enrolled are necessary to confirm these results.

Pulmonary cavitation and skin lesions mimicking tuberculosis in a HIV negative patient caused by Sporothrix brasiliensis.

A 32-year-old HIV negative male presented with multiple pulmonary cavitation and skin abscesses up to 15 cm in diameter mimicking tuberculosis. Sporothrix brasiliensis was isolated and patient responded well to amphotericin B followed by itraconazole, except the skin lesions that had to be surgical drained to obtain cure.

A comparative serological study of the SsCBF antigenic fraction isolated from three Sporothrix schenckii strains.

A previous work showed that an antigenic fraction of Sporothrix schenckii, SsCBF, was specifically recognized by IgG antibodies present in patients' clinical specimens. The objective of this investigation was to compare the reactivity of this antigen recovered from three S. schenckii strains. ROC curve analysis revealed a variation in the sensitivity and specificity of the antigen derived from each of the strains, with a higher AUC for strain 1099-18. Moreover, the presence of the main O-glycosidically-linked epitopes described in the SsCBF fraction was ascertained. A significant reduction in SsCBF reactivity of all the strains was observed after beta-elimination confirming the presence of O-glycan epitopes. The antigen isolated from strain 1099-18 proved to be a more accurate diagnostic tool for serodiagnosis of sporotrichosis.