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. Sporotrichosis is the most common and cosmopolitan subcutaneous mycosis (13). The most usual clinical manifestation of the disease is the subacute or chronic lymphocutaneous form, followed by fixed cutaneous infections (5); however, disseminated infections have also been described for those with underlying alcoholism and for immunosuppressed patients, especially those with AIDS or those receiving chemotherapy or corticoids (11,13,17). Sporotrichosis is caused by a group of species belonging to the Sporothrix schenckii complex which have various individual in vitro responses to antifungal agents. The differential antifungal activity among Sporothrix species could explain the variability in antifungal susceptibility reported for S. schenckii in studies prior to the recent recognition of the S. schenckii complex (5,20,21).The recommended procedures for the management of sporotrichosis include local measures such as hyperthermia and systemic measures such as administration of a saturated solution of potassium iodide or administration of azoles (itraconazole and fluconazole), amphotericin B, or terbinafine (15). Itraconazole has become the drug of choice for treatment of the lymphocutaneous and cutaneous forms. In those patients with intolerance to itraconazole, fluconazole is the recommended alternative. Amphotericin B is the first choice for the treatment of disseminated sporotrichosis, and itraconazole is recommended as the stepdown therapy after patients respond to the initial treatment with amphotericin B (18).Posaconazole has shown activity in vitro against the species of the S. schenckii complex (21, 25). Since treatment options for disseminated sporotrichosis are limited and there is only scarce information on the effectiveness of posaconazole in vivo, we evaluated the response to this drug in a murine model of disseminated sporotrichosis. MATERIALS AND METHODSFungi were stored in slant cultures covered with sterile paraffin oil and subcultured on potato dextrose agar (PDA) plates at 30°C for 7 days.In vitro antifungal susceptibility to posaconazole of 5 isolates of S. brasiliensis and 10 of S. schenckii sensu stricto was determined using a broth microdilution method according to the CLSI guidelines for filamentous fungi (8).For the in vivo studies, strains of S. brasiliensis (n ϭ 3) and S. schenckii sensu stricto (n ϭ 5) showing different MIC values were chosen. The inocula were prepared by...
Sporothrix luriei is a rare fungus causing sporotrichosis in humans. The virulence of this fungus was evaluated in a murine model of disseminated infection. Mice were challenged intravenously with two different inocula (2 × 10(5) and 2 × 10(7) CFU/animals) but only the highest one was able to kill the animals. Infected mice died between days 12 and 16, liver and spleen being the most affected organs. In the infected tissues, a massive infiltration of fungal cells and phagocytes were observed, but not the typical "eyeglass" cells described in infected human tissue.
The efficacy of voriconazole (VRC) was evaluated against two strains of each of the two most common species causing sporotrichosis, Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, using a murine model of disseminated infection. Voriconazole was administered at doses of 20 or 40 mg kg(-1) per day by gavage. The drug showed some efficacy, especially at 40 mg kg(-1) per day, in prolonging the survival and reducing fungal load in spleen and liver in mice infected with S. schenckii, whereas in animals infected with S. brasiliensis the drug did not work.
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