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.

Severe Sporotrichosis Treated with Amphotericin B: A 20-Year Cohort Study in an Endemic Area of Zoonotic Transmission.

Although rare, disseminated sporotrichosis is increasing in several countries. Despite its limiting toxic potential, amphotericin B is the only intravenous antifungal available to treat severe sporotrichosis. We aimed to describe the effectiveness and safety of amphotericin B treatment for severe sporotrichosis. Clinical records of patients with disseminated sporotrichosis at a reference center were reviewed. This study included 73 patients. Most (53.4%) were men and non-white. HIV coinfection was the main comorbidity (52.1%). Most reported contact with cats (76.7%). Sporothrix brasiliensis was the causative species. Affected sites were skin (98.6%), osteoarticular system (64.4%), upper airway (42.5%), central nervous system (20.5%), eyes (12.3%), and lungs (8.2%). Median doses of amphotericin B used were 750 mg and 4500 mg for deoxycholate and lipid complex formulations, respectively. Amphotericin B discontinuation occurred in 20.5% due to adverse events, mainly azotemia. The outcomes included cure (52.1%), death due to sporotrichosis (21.9%), death due to other causes (9.6%), and loss to follow-up (8.2%). Survival analysis showed an association between cure and the absence of bone, upper airway, and central nervous system involvement. Amphotericin B is the first-choice treatment for disseminated sporotrichosis; however, the severity of systemic dissemination might predict its response. Favorable clinical results depend on prompt diagnosis, investigation of fungal dissemination, and early therapy initiation.

Pulmonary Sporotrichosis Caused by Sporothrix brasiliensis: A 22-Year, Single-Center, Retrospective Cohort Study.

Pulmonary sporotrichosis is a rare condition. It can present as a primary pulmonary disease, resulting from direct Sporothrix species (spp). conidia inhalation, or as part of multifocal sporotrichosis with multiple organ involvement, mainly in immunocompromised patients. This study aimed to describe the sociodemographic and epidemiological characteristics and clinical course of patients with positive cultures for Sporothrix spp. from pulmonary specimens (sputum and/or bronchoalveolar lavage) at a reference center in an area hyperendemic for zoonotic sporotrichosis. The clinical records of these patients were reviewed. Fourteen patients were included, and Sporothrix brasiliensis was identified in all cases. Disseminated sporotrichosis was the clinical presentation in 92.9% of cases, and primary pulmonary sporotrichosis accounted for 7.1%. Comorbidities included human immunodeficiency virus infection (78.6%), alcoholism (71.4%), and chronic obstructive pulmonary disease (14.3%). Treatment with amphotericin B followed by itraconazole was the preferred regimen and was prescribed in 92.9% of cases. Sporotrichosis-related death occurred in 42.9% while 35.7% of patients were cured. In five cases there was a probable contamination from upper airway lesions. Despite the significant increase in sporotrichosis cases, pulmonary sporotrichosis remains rare. The treatment of disseminated sporotrichosis is typically difficult. Prompt diagnosis and identification of all affected organs are crucial for better prognosis.

Sporotrichosis After Tattooing Caused by Sporothrix brasiliensis.

Sporotrichosis is a subcutaneous mycosis caused by pathogenic species of the genus Sporothrix. Since 1998, the number of cases of sporotrichosis due to Sporothrix brasiliensis has grown significantly in Rio de Janeiro, Brazil. Nearly all cases are related to cats as the main source of fungal infection. We report two cases of sporotrichosis following tattoos, a transmission form of S. brasiliensis not yet reported. The first patient, a 22-year-old female, had cutaneous sporotrichosis, fixed form, over a tattoo in her lumbar region. The lesion appeared 12 weeks after she was tattooed. The second patient, a 27-year-old female, had a lymphocutaneous sporotrichosis over a forearm tattoo. The lesion appeared two weeks after she was tattooed. In both cases there was no history of contact with cats or other plausible source of infection. The present study highlights that other non-zoonotic forms of transmission of S. brasiliensis may occur in endemic areas.

Meningeal Sporotrichosis Due to Sporothrix brasiliensis: A 21-Year Cohort Study from a Brazilian Reference Center.

Meningeal sporotrichosis is rare and occurs predominantly in immunosuppressed individuals. This retrospective study explored clinical and laboratory characteristics, treatment, and prognosis of patients with disseminated sporotrichosis who underwent lumbar puncture (LP) at a Brazilian reference center from 1999 to 2020. Kaplan-Meier and Cox regression models were used to estimate overall survival and hazard ratios. Among 57 enrolled patients, 17 had meningitis. Fifteen (88.2%) had HIV infection, and in 6 of them, neurological manifestations occurred because of the immune reconstitution inflammatory syndrome (IRIS). The most frequent symptom was headache (88.2%). Meningeal symptoms at first LP were absent in 7/17 (41.2%) patients. Sporothrix was diagnosed in cerebrospinal fluid either by culture or by polymerase chain reaction in seven and four patients, respectively. All but one patient received prolonged courses of amphotericin B formulations, and seven received posaconazole, but relapses were frequent. Lethality among patients with meningitis was 64.7%, with a higher chance of death compared to those without meningitis (HR = 3.87; IC95% = 1.23;12.17). Meningeal sporotrichosis occurs mostly in people with HIV and can be associated with IRIS. Screening LP is indicated in patients with disseminated disease despite the absence of neurological complaints. Meningitis is associated with poor prognosis, and better treatment strategies are needed.

Severe Sporotrichosis Caused by Sporothrix brasiliensis: Antifungal Susceptibility and Clinical Outcomes

Itraconazole is the first choice for treating sporotrichosis. Amphotericin B is indicated for severe and disseminated forms. The aim of the study was to evaluate the antifungal susceptibility of Sporothrix brasiliensis strains isolated from patients with severe sporotrichosis treated with amphotericin B and correlate with clinical outcomes. Clinical and epidemiological data were obtained from severe sporotrichosis cases caused by S. brasiliensis. Antifungal susceptibility tests against amphotericin B, itraconazole, terbinafine, posaconazole, and 5-flucytosine were performed. Moreover, possible synergisms between amphotericin B and posaconazole or 5-flucytosine were assessed. Relationships between clinical and laboratorial data were then analyzed. Forty-six S. brasiliensis isolates from 37 patients were studied. Clinical forms included disseminated (94.6%) and disseminated cutaneous sporotrichosis (5.4%). The median treatment time was 784 days (range: 7 to 3115 days). Cure occurred in 45.9% of the cases and death due to sporotrichosis in 24.3%. Forty-three (93.5%) S. brasiliensis isolates were classified as wild-type for all the antifungals tested according to their in vitro antifungal susceptibility. There was no synergism for the combinations studied. Finally, we found no association between higher Minimal Inhibitory Concentration (MIC) values of amphotericin B or itraconazole with unfavorable outcomes; however, there were higher MIC values of itraconazole in strains isolated from alcoholic patients. Possibly, clinical factors, such as the extent of dissemination, immunosuppression, and late treatment onset, are the main determinants of patient outcomes, rather than antifungal resistance. The current study suggests that the need to use amphotericin B therapy is not associated with the emergence of S. brasiliensis resistant strains.

Zoonotic sporotrichosis in renal transplant recipients from Rio de Janeiro, Brazil.

Sporotrichosis is the main subcutaneous mycosis in the world. In the last two decades, zoonotic sporotrichosis transmitted by cats has become hyperendemic in Rio de Janeiro, Brazil. Renal transplant recipients are subject to invasive fungal infection because of the effects of immunosuppressive therapy, but sporotrichosis is rarely reported. The authors conducted a retrospective study describing epidemiological, clinical, and therapeutic data related to adult renal-transplant-recipient patients diagnosed with sporotrichosis. The molecular identification of fungal isolates was performed. Minimal inhibitory concentration (MIC) of amphotericin B (AMB), itraconazole (ITZ), posaconazole (POS), isavuconazole, and terbinafine (TRB) against the strains was determined using the protocol described by the Clinical and Laboratory Standards Institute (CLSI). Six cases were identified from a cohort with 2429 sporotrichosis patients. They were five men and one woman, with a mean age of 44.2 years (range: 34-54 years). Four of them had cutaneous limited forms, and two patients had disseminated forms. The mean time between transplant and the onset of sporotrichosis symptoms was 25.5 (range: 6-36) months. Sporothrix brasiliensis was identified as the causative agent. The isolates were classified as wild type for all antifungal drugs tested. Treatment schemes included AMB (deoxycholate and liposomal), ITZ, and TRB. Five patients evolved to cure, and one died as a result of disseminated disease. Renal transplant recipients may be a vulnerable group for sporotrichosis in endemic countries. The authors highlight the importance of sporotrichosis prevention, early diagnosis, and treatment to prevent disseminated disease and poor prognosis.

Cryosurgery for the treatment of cutaneous sporotrichosis in four pregnant women.

BACKGROUND: Pregnant women with sporotrichosis should not receive systemic antifungal therapy except in severe cases when amphotericin B is recommended. Thermotherapy is the most reported treatment described in this group of patients. It entails weeks of daily self-application of heat to the lesions, requires that the patient faithfully apply it, and it could cause skin burns. Cryosurgery is a useful therapeutic tool for many cutaneous infectious diseases, safe for pregnant women, but not well evaluated for sporotrichosis treatment in this group. METHODOLOGY: The authors conducted a retrospective study describing epidemiological, clinical, and therapeutic data related to four pregnant patients with sporotrichosis treated with cryosurgery. The authors reviewed the clinical records of four pregnant patients diagnosed with cutaneous sporotrichosis and treated with cryosurgery. The sessions were carried out monthly up to clinical cure. Molecular identification of the Sporothrix species was performed in two cases using T3B PCR fingerprinting assays. PRINCIPAL FINDINGS: All patients were in the second trimester of pregnancy and their age ranged from 18 to 34 years. With regard to clinical presentation, two patients had lymphocutaneous and two had the fixed form. S. brasiliensis was identified in two cases as the causative agent. Cryosurgery was well tolerated and the number of sessions ranged from 1 to 3. All the patients reached a complete clinical cure. CONCLUSIONS: Cryosurgery was a safe, easy to perform and well tolerated method, and therefore it is suggested to be a suitable option for the treatment of cutaneous sporotrichosis in pregnant women.