Responsible ownership and health education can reduce the time of sporotrichosis treatment in domestic cats.

Sporotrichosis is a widespread fungal infection that affects skin and subcutaneous tissues in humans and animals. In cats, it is displayed as nodules, ulcers and lesions on the nasal and respiratory mucosa. Antifungal treatment of cats is crucial but many cases are difficult, thus resulting in discontinue of the treatment, with disastrous consequences for the animal, encouraging contamination of the environment, other animals and people. The effects of responsible ownership education and health education for owners of cats with feline sporotrichosis as well as the interval between veterinary consultations on treatment outcomes for three groups of owners and their pet cats were evaluated in this study. The responsible ownership education and health education strategies consisted in videos in easy and accessible language for people with any level of education and were presented during consultations for two of the three groups included. The time between appointments was two weeks for two of the groups, and four weeks for one of the groups. The median of treatment time for the group without educational activities was 138 days, while for the other two groups it was 77.5 days and 86 days. It was found a significative reduction in the treatment time in the groups exposed to Responsible ownership education videos. There was no contamination of those responsible for home treatment, and the interval between monthly appointments did not impact on cure or death rates compared to the interval between fortnightly appointments. All these results can be applied to feline sporotrichoses treatment protocols increasing the owners treatment adherence and reducing either, the treatment discontinuation and the treatment costs and helps to control zoonotic sporotrichosis. The importance of attractive and comprehensible educational strategies as part of the feline sporotrichosis treatment protocol for the promotion of one health was highlighted.

Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats.

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

In vitro activity of the anthelmintic drug niclosamide against Sporothrix spp. strains with distinct genetic and antifungal susceptibility backgrounds.

The drugs available to treat sporotrichosis, an important yet neglected fungal infection, are limited. Some Sporothrix spp. strains present reduced susceptibility to these antifungals. Furthermore, some patients may not be indicated to use these drugs, while others may not respond to the therapy. The anthelmintic drug niclosamide is fungicidal against the Sporothrix brasiliensis type strain. This study aimed to evaluate whether niclosamide also has antifungal activity against Sporothrix globosa, Sporothrix schenckii and other S. brasiliensis strains with distinct genotypes and antifungal susceptibility status. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined using the microdilution method according to the CLSI protocol. The checkerboard method was employed to evaluate niclosamide synergism with drugs used in sporotrichosis treatment. Metabolic activity of the strains under niclosamide treatment was evaluated using the resazurin dye. Niclosamide was active against all S. brasiliensis strains (n = 17), but it was ineffective (MIC > 20 µM) for some strains (n = 4) of other pathogenic Sporothrix species. Niclosamide MIC values for Sporothrix spp. were similar for mycelial and yeast-like forms of the strains (P = 0.6604). Niclosamide was fungicidal (MFC/MIC ratio ≤ 2) for most strains studied (89%). Niclosamide activity against S. brasiliensis is independent of the fungal genotype or non-wild-type phenotypes for amphotericin B, itraconazole, or terbinafine. These antifungal drugs presented indifferent interactions with niclosamide. Niclosamide has demonstrated potential for repurposing as a treatment for sporotrichosis, particularly in S. brasiliensis cases, instigating in vivo studies to validate the in vitro findings.

Bimodal distribution of azole susceptibility in Sporothrix brasiliensis isolates in Brazil.

Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51, corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus. SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates.

Clinical characteristics, diagnosis, and treatment of central nervous system sporotrichosis: Systematic review and meta-analysis.

BACKGROUND: The clinical features of central nervous system (CNS) sporotrichosis are derived from case reports and a limited series of cases. Our objective was to carry out a systematic review and meta-analysis of CNS sporotrichosis. METHODS: We searched PubMed/MEDLINE, Embase, Scopus, and LILACS on 9 September 2023. Our inclusion criteria were documentation of Sporothrix and demonstrated CNS involvement. A metaproportion or metamean analysis was performed to estimate a summary proportion with 95% confidence intervals. RESULTS: We included 52 cases of CNS sporotrichosis published from 1966 to 2023. Forty-six patients were male (88%, 95% CI: 77-95), and the mean age was 39 years (95% CI: 36-43). Close contact with cats was reported in 55% of cases (95% CI: 37-72). Thirty-two (61.5%) patients were from Brazil, 18 patients from the United State of America (34.6%). Only two Sporothrix species were reported: S. schenckii (26/41, 63%), and S. brasiliensis (15/41, 37%). The most common neurological symptom was headache. Meningitis was chronic in approximately 80% of cases. A significant majority of the patients were immunocompromised. HIV infection was the primary cause of immunosuppression (85%, 95% CI: 61-95). Overall mortality was 56% (22/39). The comparison of Kaplan-Meier survival curve showed a higher mortality with a statistically significant difference in immunosuppressed patients (p = .019). CONCLUSION: CNS sporotrichosis represents a notable cause of chronic meningitis, especially in individuals living in the Americas with HIV infection and concurrent skin lesions.

Photodynamic therapy in the coadjuvant treatment of Sporothrix schenckii complex.

INTRODUCTION: Sporotrichosis, a zoonosis caused by animal, mainly cat, scratches or bites, is caused by fungi belonging to the Sporothrix complex. Treatment usually consists in antifungal administration, although treatment failure and hepatotoxicity reports have been noted. Alternative sporotrichosis treatment methods, such as antimicrobial photodynamic therapy (aPDT), may, therefore, be indicated. CASE REPORT: In this context, this study followed a 56-year-old male renal transplanted patient displaying disseminated sporotrichosis, presenting erythematous skin lesions with ulcerated backgrounds and hardened consistency on the nose, oral and scalp. The lesions were present for about 2 months and the patient coexisted with cats. Intravenous amphotericin B administration was initiated, and immunosuppression was suspended. Seven aPDT sessions were also performed in 48 h intervals on the oral lesions, employing 0.01% methylene blue gel as the photosensitizing agent. After the 4th aPDT session, the patient was discharged, amphotericin B administration was suspended, and the treatment was continued with itraconazole, without immunosuppression. Red laser was applied to the oral lesions after the 7th aPDT session. Significant lesion improvement was observed after the final aPDT session and complete palate lesion repair was noted after two red laser sessions. CONCLUSION: These findings indicate that aPDT is a valuable strategy as an adjunct sporotrichosis treatment.

Hyperthermia is a promising potential adjunct to treating sporotrichosis: A refractory case of HIV sporotrichosis and in vitro experiments on Sporothrix spp.

BACKGROUND: Hyperthermia is a common monotherapy for sporotrichosis, but only in patients with special conditions, such as pregnancy and nursing. However, hyperthermia has not been used more widely for sporotrichosis in clinical practice. PATIENTS/METHODS: An HIV-positive adult male with lymphocutaneous sporotrichosis caused by Sporothrix globosa that did not respond to conventional itraconazole therapy lasting >2 months received adjunctive therapy with local hyperthermia. To simulate the effects of heat exposure on the growth and morphology of Sporothrix spp. in vitro, S. globosa, S. schenckii and S. brasiliensis were exposed to intermittent heat (42°C) for 1 h a day for 7 or 28 days and observed under transmission electron microscopy. RESULTS: Itraconazole combined with local hyperthermia significantly improved the lesions, and the patient was successfully cured of sporotrichosis, with no recurrence after 2 years of follow-up. Cultures of Sporothrix spp. treated with 7 days of daily heat exposure in vitro showed obvious decreases in colony diameters, but not numbers, compared with untreated cultures (p < .001). After 28 days of heat exposure in vitro, Sporothrix spp. were unable to thrive (p < .001), and ultrastructural alterations, including loose cell wall structure, incomplete cell membrane, disrupted vacuoles and fragmented nuclei, were noticeable. CONCLUSIONS: Our case findings and in vitro experiments on Sporothrix spp., together with a literature review of previous sporotrichosis cases, suggest that hyperthermia has a clinical role as a treatment adjunct. Large-scale clinical trials are required to examine the utility of hyperthermia in various forms of cutaneous sporotrichosis.

Sporotrichosis in a Renal Transplant Patient: A Rare Case Report with a Review of the Literature.

Sporotrichosis is a rare form of subacute and chronic fungal infection in renal transplant recipients caused by the ubiquitous fungus Sporothrix schenckii. It is usually described in renal allograft recipients who have not been treated with antifungal prophylaxis. We report a rare case of cutaneous sporotrichosis in a 39-year-old renal allograft recipient already on antifungal prophylaxis, who presented with skin lesions. The diagnosis was made from a skin biopsy. The patient had increased tacrolimus levels after starting treatment with itraconazole, which was later changed to terbinafine and cryotherapy. The patient responded to treatment with regression of his lesions.

Case Report: Osteomyelitis Due to Sporothrix brasiliensis in Two Immunocompetent Patients Requiring Surgical Amputation.

Sporotrichosis is the most frequent subcutaneous mycosis in Latin America. Sporothrix brasiliensis is the most virulent species, responsible for the majority of human and animal cases in Brazil. Osteomyelitis was described as a potential comorbidity of S. brasiliensis infection; however, surgical amputation resulting from an extracutaneous form is a rare outcome. In such cases, immunodeficiency and alcoholism must be investigated. We present two unusual cases of surgical amputation as a severe morbidity resulting from osteomyelitis by S. brasiliensis in immunocompetent nonalcoholic patients.

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.

Cutaneous disseminated sporotrichosis associated with diabetes: A case report and literature review.

BACKGROUND: Cutaneous disseminated sporotrichosis (CDS), also called hematogenous sporotrichosis, is a rare condition that usually affects immunocompromised patients. The current work presents the case of a woman with diabetes mellitus associated with CDS. CASE PRESENTATION: A 59-year-old woman with diabetes mellitus presented with a two-year history of ulcerated rashes on the left ankle and both sides of the jaw. Physical examination revealed three annular areas of erythematous and raised plaque with an ulcer over the left ankle and both sides of the jaw. Based on laboratory findings, elevated blood glucose concentration and decreased white cell count were observed. Sporothrix globosa was identified in the mycological culture of biopsied tissue from the three lesions and this was confirmed by DNA sequencing. The skin lesions healed after two-month itraconazole therapy. CONCLUSIONS: Diabetes is a risk factor for disseminated sporotrichosis, which may be induced by hematogeneous spread, repeated inoculation, or autoinoculation. This study raises awareness among clinicians, with regard to the notion that people with possibly altered immune function are potentially vulnerable to severe clinical forms of sporotrichosis.

Nikkomycin Z for the treatment of experimental sporotrichosis caused by Sporothrix brasiliensis.

Sporotrichosis caused by Sporothrix brasiliensis is a global emergent infectious disease. Due to the scarcity of therapeutic options for fungal diseases, new antifungals are urgently needed. Nikkomycin Z (NikZ) is a future option as an agent against dimorphic fungi. We evaluated NikZ monotherapy and in combination with itraconazole (ITZ; the conventional therapy) in the treatment of experimental sporotrichosis caused by S. brasiliensis in a murine model. Animals were subcutaneously infected, and treated orally for 30 days. The study groups were as follows control (untreated), ITZ group (50 mg/kg/day), and three groups treated with NikZ, two by monotherapy (200 or 400 mg/kg/day), and one combining NikZ (400 mg/kg/day) and ITZ. Efficacy of treatments was evaluated via body weight gain, mortality and fungal burden in tissues. Efficacy was noted in all treatment groups, and the group receiving the drug combination showed even better results than those with monotherapy. Our study shows for the first time the high potential of NikZ to be used in the treatment of sporotrichosis caused by S. brasiliensis.

Epidemiological and clinical aspects of sporotrichosis in patients seen at a reference hospital in Madagascar.

INTRODUCTION: Sporotrichosis is a subacute to chronic fungal infection of skin and subcutaneous tissues, caused by dimorphic fungi belonging to the genus Sporothrix, commonly seen in tropical and subtropical regions like Madagascar. This study describes the epidemiological, clinical, and the treatment outcomes with itraconazole for sporotrichosis. METHODS: A descriptive retrospective study on patients suffering from sporotrichosis, from March 2013 to January 2019, was conducted, in the reference center for endemic mycoses. Patients with sporotrichosis who received itraconazole for at least 3 months were included in the study. Patients received itraconazole 200 mg daily for 3 to 6 months. Therapeutic responses were evaluated at months 3 and 6 after treatment. Outcomes were classified as minor response, major response, cure, and failure. RESULTS: Forty-three cases of sporotrichosis were included. The median age of patients was 40 years. Most of them (62.8%) were rural workers. Men were more frequently infected (72%). At the end of 6th month of treatment, 20 patients (46.5%) were cured and a major response to itraconazole was observed in 8 patients (18.6%). The cure rate was higher in 12 patients (27.9%) who had disease durations of less than to one year than in those who had more time of disease (18.6%) (p = 0.01). Thirteen patients (30.2%) were lost to follow up. The rate of lost to follow-up was also higher (39.5%) in patients who had sporotrichosis of less than to one year than in those who had more time of disease. CONCLUSION: The cure rate found in this study was inferior to that reported in the literature. However, it was higher in patients with early symptomatology.

Intramedullary disseminated sporotrichosis in an immunocompetent patient: case report and review of the literature.

BACKGROUND: Disseminated sporotrichosis is a severe opportunistic infection that often affects immunocompromised patients after a cutaneous inoculation. Here we present a rare case of disseminated sporotrichosis discovered as a solitary intramedullary thoracic spinal cord lesion in an immunocompetent patient. CASE DESCRIPTION: A 37-year-old man presented with progressive lower limb weakness and sensory changes over 1 week. A spinal magnetic resonance imaging (MRI) revealed a contrast-enhancing intramedullary lesion centered at T10. The patient was afebrile and reported no history of trauma or cutaneous lesions. The lesion was unresponsive to a trial of corticosteroids. A thoracic laminectomy was performed and a biopsy obtained. A cutaneous lesion on the arm was concurrently discovered, which was also biopsied. Both the skin and spinal cord biopsies showed Sporothrix schenckii by macroscopic and microscopic morphology which were later confirmed by MALDI-TOF mass spectrometry. CONCLUSION: This is a rare case of intramedullary disseminated sporotrichosis affecting the central nervous system of an immunocompetent patient. This unusual presentation should be taken into consideration when such intramedullary lesions are encountered.

Emergence of zoonotic sporotrichosis due to Sporothrix brasiliensis in Minas Gerais, Brazil: A molecular approach to the current animal disease.

Sporotrichosis is a neglected fungal zoonosis with significant impacts on human and animal health. Accurate diagnosis, treatment, and understanding of the transmission dynamics of Sporothrix species are essential for mitigating the spread of sporotrichosis. This study aimed to identify the Sporothrix species involved in the ongoing outbreaks of animal sporotrichosis in the metropolitan region of Belo Horizonte, Minas Gerais, Brazil, and analyse the phylogenetic relationships between pathogenic species to investigate the outbreak origin. Additionally, to better understand the evolution of the disease, we conducted a retrospective survey of positive feline and canine cases from November 2017 to July 2021 with proven cultures for Sporothrix. A significant increase in animal cases over the last 4 years was observed, with cats being the most affected host. Sporothrix brasiliensis was the predominant agent in 100% of the clinical isolates (n = 180) molecularly identified. Phylogenetic and haplotype analysis points towards the cases isolated from Minas Gerais sharing the haplotype originating from a long-lasting outbreak of cat-transmitted sporotrichosis in Rio de Janeiro, however, with a secondary contribution from genotypes circulating in other outbreaks in Brazil. Thus, we present clear evidence of the circulation of different S. brasiliensis genotypes associated with animal sporotrichosis in the metropolitan region of Belo Horizonte. Genetic monitoring can contribute to understanding the causal agent for zoonotic sporotrichosis in epidemiological processes and help to implement disease prevention and control measures.

Sporotrichosis co-infection with human immunodeficiency virus/acquired immunodeficiency syndrome.

Sporotrichosis is a subcutaneous mycosis caused by a dimorphic fungus belonging to the genus Sporothrix. This fungal infection can affect both humans and domestic animals, and in recent years, an increase in the geographic spread and prevalence of sporotrichosis has been observed globally. This systematic review aimed to examine the clinical-epidemiological and therapeutic aspects related to sporotrichosis co-infection with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). An extensive electronic search was conducted on databases including PubMed, Web of Science, Lilacs, Medline, Embase, Scopus and SciELO was performed to identify clinical cases of people living with HIV (PLWH) with sporotrichosis published until May 2023. As a result, we found that most co-infected patients were male, representing 71.76% (94/131) of cases. The most prevalent age group was 41-50 years, with a mean age of 36.98 years. The countries with the highest number of cases were Brazil (75.57%, 99/131) and the United States (16.03%, 21/131). The most frequent clinical presentation was systemic dissemination, accounting for 69.47% (91/131) of the cases, followed by cutaneous dissemination with 13% (17/131). The mean CD4+ cell count was 154.07 cells/µL, and most patients used amphotericin B with at least one azole, which represented 47.33% (62/131) of cases, followed by azole monotherapy in 17.56% (23/131) of cases. As for the outcome, 51.15% (67/131) of the patients remained alive, and 37.4% (49/131) died. Therefore, it was concluded that sporotrichosis in PLWH is a disease with a high prevalence in Brazil and may be associated with systemic clinical manifestations requiring longer periods of systemic antifungal therapy.

Severe form of lymphocutaneous sporotrichosis: a case report.

Sporotrichosis is the most frequent subcutaneous mycosis in Latin America. It is caused by species of the genus Sporothrix. Infection in humans occurs through the entry of the fungus into the skin. Zoonotic outbreaks involving cats in the transmission of the disease have been frequently reported. The lymphocutaneous form is the most commonly observed and the upper limbs are the most affected sites. We report a case of a 64-year-old healthy female patient with a lymphocutaneous form with rapid progression of lesions, which was refractory to initial treatment with itraconazole. Treatment with liposomal amphotericin B was performed with a satisfactory resolution, but aesthetic and functional sequelae in the left upper limb were installed.