The fungus Saprochaete capitata causes opportunistic human infections, mainly in immunocompromised patients with hematological malignancies. The best therapy for this severe infection is still unknown. We evaluated the in vitro killing activity and the in vivo efficacy of posaconazole at 5, 10, or 20 mg/kg twice a day (BID) in a murine neutropenic model of systemic infection with S. capitata by testing a set of six clinical isolates. Posaconazole showed fungistatic activity against all of the isolates tested. The different doses of the drug, especially the highest one, showed good efficacy, measured by prolonged survival, reduction of (1-3)--D-glucan levels in serum, tissue burden reduction, and histopathology.
Saprochaete capitata, formerly known as Trichosporom capitatum, Geotrichum capitatum, and Blastoschizomyces capitatus, is an uncommon clinical fungus belonging to the phylum Basidiomycota, but it is able to cause fatal fungemia in immunocompromised patients, especially in those with hematological malignancies (1-6). The therapeutic options against these infections are limited, because S. capitata is considered intrinsically resistant to the echinocandins (7-10). Currently, there are no recommendations for the management of infections caused by S. capitata, although amphotericin B is the drug most commonly used in the clinical setting, followed by itraconazole and voriconazole (9,(11)(12)(13)(14). The use of these compounds is supported by the in vitro antifungal susceptibility of S. capitata to such drugs. However, despite treatment, the mortality rate still remains high, at around 60% (5, 15-19), making it necessary to explore new therapeutic approaches. In previous studies conducted on mice, high doses of fluconazole demonstrated higher efficacy than amphotericin B, flucytosine, and voriconazole (20). Posaconazole has not been evaluated against this fungal species before but has shown efficacy in experimental infections against a wide range of opportunistic fungi, such as Aspergillus spp., Curvularia spp., Rhizopus oryzae (21,22,23), and others, including Trichosporon asahii, which is taxonomically related to S. capitata (24). In the present study, we evaluated the in vitro killing activity of posaconazole against this fungus as well as its in vivo efficacy in a neutropenic murine model of systemic infection by S. capitata. (IHEM 5665, IHEM 5666, IHEM 5091, IHEM 6803, IHEM 16105, and IHEM 16109) were included in this study. The inocula were prepared from potato dextrose agar (PDA) cultures by flooding the plates with 3 ml of sterile saline solution and scraping the surface of the colonies with a loop in order to obtain a conidial suspension. To remove hyphal fragments and clumps of agar, the resulting suspension was filtered twice through sterile gauze and then adjusted by hemocytometer counts to the desired concentrations. Viability of inocula was determined by placing 10-fold dilutions of the conidial suspension on PDA plates.
MATERIALS AND METHODS
Strains and inocula. Six clinical strains of S. ca...