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.

Ethyl acetate fractions of Myrciaria floribunda, Ocotea pulchella, and Ocotea notata exhibit promising in vitro activity against Sporothrix brasiliensis isolates with low susceptibility to itraconazole.

Sporothrix brasiliensis with low susceptibility isolates were described from the Brazilian zoonotic sporotrichosis hyperendemics. The aim of this work was to evaluate distinct fractions of Ocotea pulchella, Ocotea notata, Myrciaria floribunda, and Hypericum brasiliense plant extracts against itraconazole-sensitive and low susceptibility S. brasiliensis isolates. Crude extracts were tested against clinical isolates and the ATCC MYA4823 to determine the minimum inhibitory concentrations (MICs) and fungicidal or fungistatic activities (MFC). A high MICs and MFCs amplitude (1 - > 128 µg/mL) were obtained for seven extracts. The highest antimicrobial activities against sensitive S. brasiliensis were displayed by the ethyl acetate extracts of O. notata (MIC = 2-128 µg/mL) and M. floribunda (MIC = 1-8 µg/mL). A fungicidal effect was observed for all fraction extracts. Ocotea spp. and M. floribunda ethyl acetate extracts provide promising profiles against itraconazole-sensitive or low susceptibility S. brasiliensis. Future studies will determine if these extracts can contribute as alternative therapies to this neglected zoonosis.

Withania somnifera (L.) Dunal whole-plant extracts exhibited anti-sporotrichotic effects by destabilizing peripheral integrity of Sporothrix globosa yeast cells.

Chronic topical cases of Sporotrichosis, a chronic fungal infection caused by the ubiquitously present cryptic members of the Sporothrix species complex, are treated with oral administrations of itraconazole. However, severe pulmonary or disseminated cases require repeated intra-venous doses of amphotericin B or even surgical debridement of the infected tissue. The unavoidable adverse side-effects of the current treatments, besides the growing drug resistance among Sporothrix genus, demands exploration of alternative therapeutic options. Medicinal herbs, due to their multi-targeting capacity, are gaining popularity amidst the rising antimicrobial recalcitrance. Withania somnifera is a well-known medicinal herb with reported antifungal activities against several pathogenic fungal genera. In this study, the antifungal effect of the whole plant extract of W. somnifera (WSWE) has been explored for the first time, against an itraconazole resistant strain of S. globosa. WSWE treatment inhibited S. globosa yeast form growth in a dose-dependent manner, with IC50 of 1.40 mg/ml. Minimum fungicidal concentration (MFC) was found to be 50 mg/ml. Sorbitol protection and ergosterol binding assays, revealed that anti-sporotrichotic effects of WSWE correlated well with the destabilization of the fungal cell wall and cell membrane. This observation was validated through dose-dependent decrease in overall ergosterol contents in WSWE-treated S. globosa cells. Compositional analysis of WSWE through high performance liquid chromatography (HPLC) exhibited the presence of several anti-microbial phytochemicals like withanone, withaferin A, withanolides A and B, and withanoside IV and V. Withanone and withaferin A, purified from WSWE, were 10-20 folds more potent against S. globosa than WSWE, thus, suggesting to be the major phytocompounds responsible for the observed anti-sporotrichotic activity. In conclusion, this study has demonstrated the anti-sporotrichotic property of the whole plant extract of W. somnifera against S. globosa that could be further explored for the development of a natural antifungal agent against chronic Sporotrichosis.

Feline sporotrichosis: a case series of itraconazole-resistant Sporothrix brasiliensis infection.

The treatment of feline sporotrichosis is a challenge for veterinary clinicians since refractory cases may occur, due either to patient and/or to pharmacological management errors or due to the development of antifungal resistance. Thus, we aimed to describe the therapeutic history of feline cases infected by itraconazole-resistant Sporothrix brasiliensis in an endemic region of Southern Brazil. Medical records of cats attended at the Veterinary Clinic Hospital (Pelotas/RS, Brazil) between 2016 and 2017 were reviewed. Twelve cases of infection by S. brasiliensis with that showed high minimum inhibitory concentration (MIC) values (≥ 4 µg/mL) to itraconazole by M38-A2 of CLSI were selected. At the hospital consultation, disseminated (cats 1-l0, 12) and localized (cat 11) skin lesions remained in the cats, even after treatment with fluconazole, ketoconazole (02/12), and itraconazole (ITZ, 09/12) performed before this study. High doses (25-100 mg/kg/day) of ITZ for up to 4 months (03/12, cats 2, 6, 12) or over 12 months (05/12, cats 1, 5, 7, 8, 11) did not provide a clinical cure, except for the association of ITZ plus potassium iodide (01/12, cat 12) for 3 months, which proved useful in infections with itraconazole-resistant S. brasiliensis. However, the combined issues of abandonment of therapy by owners for financial reasons, difficulties surrounding therapy administration (03/12, cats 6, 11, 12), and the inappropriate choice of medication (01/12, cat 6), together reflect the reality of this endemic region, which greatly compromises clinical healing. This study highlighted the occurrence of refractory cases by itraconazole-resistant S. brasiliensis in cats from Southern Brazil, as well as the abandonment of treatment and therapeutic errors. We warn of the need for antifungal susceptibility tests to adapt therapeutic protocols in feline sporotrichosis.

5-Aminolevulinic acid-mediated photodynamic therapy has effective antifungal activity against Sporothrix globosa in vitro.

BACKGROUND: An alternative therapy for sporotrichosis is necessary to reduce the treatment time and raise clinical efficacy. The 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a promising platform with which to treat mycoses. However, despite the worldwide prevalence of Sporothrix globosa, a causative agent of sporotrichosis, the effect of ALA-PDT on this pathogen has not been validated. OBJECTIVES: The aim of this study was to evaluate the effect of ALA-PDT on S globosa and the protection of melanin through an in vitro study. The mechanisms involved were also investigated. METHODS: To estimate the survival rate of S globosa treated with ALA-PDT and the protection offered by melanin, the conidia and yeast cells of wild-type S globosa (Mel+), other clinical strains, tricyclazole-treated Mel+ and an albino mutant strain (Mel-) were incubated with and without ALA or irradiation. Reactive oxygen species generation by Mel+ conidia induced by ALA-PDT was assayed. SEM and TEM were conducted to obverse ultrastructural changes in the conidia. A comet assay was performed to evaluate DNA damage. RESULTS: The survival rate of S globosa conidia and yeast cells significantly decreased following incubation with 1.19M ALA and 162 J/cm2 irradiation in vitro. Melanin was not only capable of protecting the conidia against ALA-PDT, but also against ALA or irradiation alone. After induction by ALA-PDT, alterations in reactive oxygen species generation, DNA damage and ultrastructural changes were observed. CONCLUSIONS: ALA-PDT inhibits the survival of S globosa conidia in vitro and therefore has potential for the treatment of sporotrichosis.

Sporotrichosis caused by Sporothrix brasiliensis in Argentina: Case report, molecular identification and in vitro susceptibility pattern to antifungal drugs.

Sporotrichosis is considered a neglected disease of humans and animals in many regions of the world and is the most frequent implantation mycosis in Latin America. OBJECTIVES: To illustrate the zoonotic importance of the disease, describing a case involving a veterinarian and an infant that acquired the disease from a domestic cat and to describe, genotype and characterize these new isolates. METHODS: Direct examination of tissue samples from the two patients and feline lesions revealed the presence of Sporothrix yeast-like organisms. Fungal cultures and molecular identification of the strains were performed. Since antifungal susceptibility data of animal-borne isolates are scarce, the in vitro susceptibility testing by a microdilution reference method was determined against azoles, amphotericin B and terbinafine. RESULTS: Fungal culture and sequence analysis of the ITS region of rDNA and calmodulin and ß-tubulin genes confirmed the diagnosis and the causative agent as Sporothrix brasiliensis. In all cases, terbinafine was the most active drug, followed by posaconazole, itraconazole and voriconazole; the least active drugs were amphotericine B and fluconazole. Lack of clinical response in the veterinarian and in the infant to itraconazole and potassium iodide, respectively was observed. CONCLUSIONS: This study contributed to the molecular epidemiology of Sporothrix species in Argentina and the characterization of the in vitro susceptibility pattern of S. brasiliensis isolates recovered from a cat and two humans involved in this case of zoonotic sporotrichosis. Bearing in mind the "One Health" concept, the experience described in the present study highlights the need for future strategies for sporotrichosis treatment, control and prevention.

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.

Polar Origanum vulgare (Lamiaceae) extracts with antifungal potential against Sporothrix brasiliensis.

Oregano (Origanum vulgare) has anti-Sporothrix spp. activity, including against strains that are resistant to antifungal drugs. As the studies are limited to the essential oil, the aim of this study was to evaluate the chemical, antioxidant and cytotoxic properties of polar oregano extracts and their anti-Sporothrix brasiliensis activity. Aerial plant parts were used in the preparation of 10 min (INF10) and 60 min (INF60) infusions, a decoction (DEC) and a hydroalcoholic extract (HAE). Six phenolic acids and four flavonoids were identified and quantified through liquid-chromatography (LC-MS). Extracts in increasing order of total phenolic and flavonoid contents were HAE 40 mg/ml for the other extracts. This is the first report of oregano extracts showing antifungal activity against S. brasiliensis. Its use in the treatment of sporotrichosis may be considered upon toxicity and safe-use conditions are tested.

Comparison of two in vitro antifungal sensitivity tests and monitoring during therapy of Sporothrix schenckii sensu stricto in Malaysian cats.

BACKGROUND: Feline sporotrichosis is common in Malaysia. Thermosensitivity and effects of azole treatment on fungal susceptibility are unknown. OBJECTIVES: To evaluate thermotolerance and antifungal susceptibility of feline Malaysian Sporothrix isolates, compare microdilution (MD) and E-test results, and investigate changes in susceptibility during azole therapy. METHODS: Sporothrix schenckii sensu stricto was isolated from 44 cats. Thermotolerance was determined via culture at 37°C for 7 days. Susceptibility to itraconazole (ITZ), ketoconazole (KTZ) and terbinafine (TRB) was assessed in 40 isolates by MD; to amphotericin B (AMB), KTZ, ITZ, fluconazole (FLC) and posaconazole (POS) by E-test. Results were statistically compared by Pearson's Product Moment. In eight ketoconazole treated cats, susceptibility testing to itraconazole and ketoconazole was repeated every two months for six months. RESULTS: Thermotolerance was observed in 36 of 44 (82%) isolates. Assuming that isolates growing at antifungal concentrations ≥4 mg/mL were resistant, all were resistant on E-test to FLC and AMB, 11 (28%) to POS, 6 (15%) to ITZ and 1 (3%) to KTZ. On MD, 27 of 40 (68%) were resistant to TRB, 2 (5%) to ITZ and 3 (8%) to KTZ. There was no correlation between E-test and MD results (KTZ r = 0.10, P = 0.54, and ITZ r = 0.11, P = 0.48). MD values for ITZ and KTZ did not exceed 4 mg/L during KTZ therapy. CONCLUSION: The majority of feline isolates in Malaysia are thermosensitive. Lack of correlation between E-test and MD suggests that the E-test is unreliable to test antifungal susceptibility for Sporothrix spp. compared to MD. KTZ was the antifungal drug with the lowest MIC. Prolonged KTZ administration may not induce changes in antifungal susceptibility.

Anti-inflammatory activity of Vismia guianensis (Aubl.) Pers. extracts and antifungal activity against Sporothrix schenckii.

ETHNOPHARMACOLOGICAL RELEVANCE: Vismia guianensis (Aubl.) Pers. is traditionally used in North and Northeast of Brazil for the treatment of dermatomycoses. Since the strategy associating immunomodulators with antifungal drugs seems to be promissory to improve the treatment efficacy in fungal infections, we aimed to investigate the antifungal activity of V. guianensis ethanolic extract of leaves (VGL) and bark (VGB) against Sporothrix schenckii ATCC 16345 and their antinflammatory activities. MATERIAL AND METHODS: The extracts were analyzed by HPLC-DAD-IT MS/MS for in situ identification of major compounds. Antifungal activity was evaluated in vitro (microdilution test) and in vivo using a murine model of S. schenckii infection. The production of TNF-α, IFN-γ, IL-4, IL-10 and IL-12 by measured by ELISA, as well as measured the production and inhibition of the NO after treatment with the plant extracts or itraconazole (ITR). RESULTS: Two O-glucosyl-flavonoids and 16 prenylated benzophenone derivatives already described for Vismia were detected. Both VGL and VGB showed significant antifungal activity either in in vitro assay of microdilution (MIC=3.9µg/mL) and in vivo model of infection with reduction of S. schenckii load in spleen. It was also observed a predominance of reduction in the production of NO and the proinflammatory cytokines evaluated except TNFα, but with stimulation of IL-10, as evidence of a potential anti-inflammatory effect associated. CONCLUSION: The results showed that both VGL and VGB have a significant antifungal against S. schenckii and an anti-inflammatory activity. These results can support the use of these extracts for alternative treatment of sporotrichosis.

Refractory sporotrichosis due to Sporothrix brasiliensis in humans appears to be unrelated to in vivo resistance.

Sporotrichosis is a subacute to chronic infection caused by members of the Sporothrix schenckii complex. Itraconazole is the first choice antifungal drug for treating this infection, with terbinafine and potassium iodide as alternatives and amphotericin B used in cases of severe infections. Correlation of antifungal susceptibility data with the clinical outcome of the patients is scarce. The aim of this study was to correlate clinical and mycological data in patients with refractory sporotrichosis. In this work, antifungal susceptibilities, determined according to the reference M38-A2 CLSI protocol, of 25 Sporothrix strains, isolated from seven human cases of sporotrichosis with adversities in the treatment, are presented. Tested drugs included itraconazole, ketoconazole, posaconazole, voriconazole, terbinafine, and amphotericin B. Fungi were identified using the T3B PCR fingerprinting. This method identified all strains as Sporothrix brasiliensis and also demonstrated a high degree of similarity between the strains. In general, voriconazole was ineffective against all strains, and elevated minimal inhibitory concentrations (MICs) were observed for amphotericin B. High itraconazole and terbinafine MICs were not observed in S. brasiliensis isolates from patients of this study. Moreover, a significant increase in itraconazole and terbinafine MIC values from strains isolated from the same patient in different periods was not observed. The results suggest that the antifungal susceptibility to terbinafine and itraconazole determined by the reference method does not play an important role in therapeutic failure of sporotrichosis and that acquisition of resistance during prolonged antifungal treatment is not likely to occur in S. brasiliensis.

In Vitro Susceptibility of Sporothrix brasiliensis to Essential Oils of Lamiaceae Family.

This study evaluated the chemical, cytotoxic and anti-Sporothrix brasiliensis properties of commercial essential oils of rosemary (Rosmarinus officinalis L.), oregano (Origanum vulgare L.) and marjoram (Origanum majorana L.). Chemical composition of the oils was identified through gas chromatography with flame ionization detector, and cytotoxicity was performed through MTT assay in VERO cell line. Anti-S. brasiliensis activity was performed according to the CLSI M38-A2 guidelines using isolates obtained from cats and dogs. The major compounds found were carvacrol in the oregano oil (73.9 %) and 1,8-cineole in rosemary and marjoram oils (49.4 and 20.9 %, respectively). All S. brasiliensis isolates were susceptible to the plant oils, including itraconazole-resistant ones. Marjoram and rosemary oils showed MIC90 of 0.56 and 1.12 mg ml-1, and MFC90 of 4.5 and 9 mg ml-1, respectively. For oregano oil, a strong antifungal activity was observed with MIC90 and MFC90 values ≤0.07 mg ml-1. The weakest cytotoxicity was observed for rosemary oil. Further studies should be undertaken to evaluate the safety and efficacy of these essential oils in sporotrichosis.

Two cases of sporotrichosis of the right upper extremity in right-handed patients with diabetes mellitus / Dos casos de esporotricosis de la extremidad superior derecha en pacientes diestros con diabetes mellitus

Background. Sporothrix species have proved to show high degrees of endemicity. Sporothrix globosa is the only pathogenic Sporothrix species that has till date been reported from China, where it is endemic in the northeastern provinces. Aims. We report two cases of lymphocutaneous sporotrichosis with diabetes mellitus as underlying disease in patients from the non-endemic area of China. Methods. A 59-year-old farmer and a 60-year-old gardener were admitted in February and June 2014, respectively. Both patients were right-handed men and presented with progressive plaques and nodules, which they had for several years, involving the right upper extremity. Skin biopsy from the granuloma was taken and cultured on Sabouraud medium, and molecular identification based on the calmodulin region was performed. Antifungal susceptibility testing was also performed with the microdilution method. Results. Biopsy of the lesions showed the presence of infectious granuloma. The fungal cultures were identified as Sporothrix globosa by conventional methods, and confirmed by molecular identification. A subsequent course of oral antifungal therapy with low dosage of itraconazole was well tolerated and resolved the infection. Conclusions. Identification of fungal species and antifungal susceptibility testing are mandatory for epidemiological and therapeutic reasons. Early diagnosis of sporotrichosis is essential to prevent those sequelae when the disease progresses and provides highly effective methods for treating this emerging disease. Avoiding the exposure to plant material potentially contaminated with fungal spores should be recommended, especially in immunocompromised patients (AU)

Antecedentes. Las especies de Sporothrix han demostrado un alto nivel de endemicidad. Sporothrix globosa es la única especie patógena descrita hasta la fecha en China, donde es endémica en las provincias del nordeste. Objetivos. Se describen dos casos de esporotricosis linfocutánea con diabetes mellitus como enfermedad de base, en pacientes procedentes de un área no endémica de China. Métodos. Un campesino de 59 años y un jardinero de 60 años de edad fueron atendidos en febrero y junio de 2014, respectivamente. Ambos eran varones, diestros y se presentaron con placas y nódulos de varios años de evolución, que afectaban a la zona superior del brazo derecho. Se tomaron biopsias de los granulomas de la piel, que fueron cultivados en medio de Sabouraud, y se realizó una identificación molecular basada en la región de la calmodulina. Se evaluó la sensibilidad a los antifúngicos mediante el método de microdilución. Resultados. La biopsia de las lesiones mostró la presencia de un granuloma infeccioso. Los hongos aislados en los cultivos fueron identificados como Sporothrix globosa por métodos convencionales, y confirmados mediante identificación molecular. La subsecuente administración de terapia antifúngica oral con bajas dosis de itraconazol fue bien tolerada y resolvió la infección. Conclusiones. La identificación de las especies fúngicas y el análisis de la sensibilidad a los antifúngicos son necesarios por razones epidemiológicas y terapéuticas. El diagnóstico temprano de la esporotricosis es esencial para prevenir las secuelas que genera el progreso de la enfermedad y para ofrecer métodos altamente efectivos para el tratamiento de esta enfermedad emergente. Debe recomendarse evitar la exposición a material vegetal potencialmente contaminado con esporas fúngicas, especialmente en pacientes inmunocomprometidos (AU)

Efficacy of posaconazole in murine experimental sporotrichosis.

We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.

Successful treatment of terbinafine in a case of sporotrichosis.

Sporotrichosis is a chronic subacute infection caused by fungi belonging to the Sporothrix Complex. In the present clinical case, nasal sporotrichosis was treated with potassium iodide. This was unsuccessful, and the treatment was restarted with a combination of potassium iodide and itraconazole. This however resulted in a further recurrence of the infection. The mycological cultures were tested in vitro for antifungal activity to assist in treatment. Terbinafine, an antifungal drug, produced the best results and was therefore used for the rest of the treatment course, with no recurrence after two years of its completion. In addition, both cultures were compared using RAPD and different fragment patterns were observed. This indicated that the isolates were either different or indicated a microevolutionary process of this microorganism.

Sucesso terapêutico da terbinafina em um caso de esporotricose / Successful treatment of terbinafine in a case of sporotrichosis

A esporotricose é uma infecção subaguda ou crônica, causada por fungos pertencentes ao Complexo Sporothrix. Relato do caso: esporotricose de localização nasal foi tratada com iodeto de potássio e como não se obteve sucesso, reiniciou-se o tratamento com associação de iodeto de potássio e itraconazol. Porém, ocorreu nova recidiva. As culturas dos exames micológicos foram submetidas a ensaios de atividade antifúngica in vitro para auxiliar no tratamento. A terbinafina foi o antifúngico que apresentou melhores resultados, por isso, o tratamento foi reiniciado com este antifúngico e, após dois anos do término do mesmo, não recidivou. Adicionalmente, ambas as culturas foram comparadas por RAPD, obtendo padrões de fragmentos distintos, indicando que os isolados são diferentes ou demonstrando um processo microevolutivo do microrganismo.

Sporotrichosis is a chronic subacute infection caused by fungi belonging to the Sporothrix Complex. In the present clinical case, nasal sporotrichosis was treated with potassium iodide. This was unsuccessful, and the treatment was restarted with a combination of potassium iodide and itraconazole. This however resulted in a further recurrence of the infection. The mycological cultures were tested in vitro for antifungal activity to assist in treatment. Terbinafine, an antifungal drug, produced the best results and was therefore used for the rest of the treatment course, with no recurrence after two years of its completion. In addition, both cultures were compared using RAPD and different fragment patterns were observed. This indicated that the isolates were either different or indicated a microevolutionary process of this microorganism.

Sporotrichosis: an update.

Sporotrichosis is the most frequent and worldwide distributed subcutaneous mycoses. The aim of this article is to review the most recent aspects of sporotrichosis about its epidemiology, etiologic agents, mycologic characteristics, clinical features, diagnosis and treatment. The causative agents of sporotrichosis belong to five well defined species of dimorphic fungi of the called Sporothrix schenckii complex. Sporotrichosis and its etiologic agents have specific endemic areas, but it is possible to find epidemics of the disease in practically every continent, the entrance via is cutaneous due to the inoculation of the fungi into the skin after a traumatism and less frequent due to respiratory way. Clinical manifestations are widely variable, with important involvement of the skin and the superficial lymphatic system, but also with affection of the mucosa and some organs like lungs, bones and joints. Nowadays sporotrichosis is considered a true zoonosis with important changes related to the endemic areas and the ecologic features of the causative pathogens. The therapy of choice is the potassium iodide (KI), but other alternatives are itraconazole, terbinafine, thermotherapy and in severe cases amphotericin B. The importance of the recognition of the clinical manifestations of the disease in some non-endemic areas helps to challenge the diagnosis and give an accurate therapy.