Therapeutic efficacy of posaconazole in a murine model of disseminated trichosporonosis

• Published in: Journal of antimicrobial chemotherapy 2014-04, Vol.69 (4), p.1075-1078
• Main Authors: Trevino-Rangel, R. d. J., Lopez, L. J., Palma-Nicolas, J. P., Hernandez-Bello, R., Gonzalez, J. G., Gonzalez, G. M.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Amphotericin B - therapeutic use; Animals; Antifungal Agents - therapeutic use; Colony Count, Microbial; Drug therapy; Fluconazole - therapeutic use; Fungal infections; Fungi; Injections, Intraperitoneal; Kidney - microbiology; Liver - microbiology; Male; Mice; Mice, Inbred BALB C; Pharmaceuticals; Rodents; Spleen - microbiology; Treatment Outcome; Triazoles - therapeutic use; Trichosporon - drug effects; Trichosporonosis - drug therapy
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkt466

Objectives To study the effect of the initiation time of posaconazole treatment from 1 to 3 days after systemic infection by Trichosporon asahii in mice. Methods BALB/c mice, 4–5 weeks old, were intravenously infected with 1 × 107 cfu/mouse of T. asahii. The onset of treatment varied from 1 to 3 days after infection. Orally administered posaconazole at 0.5, 1, 2, 5 or 10 mg/kg body weight/day was compared with orally administered fluconazole (at 10 mg/kg/day) and intraperitoneally administered amphotericin B (at 1 mg/kg) on alternating days. Livers, kidneys and spleens of mice that died or survived to day 25 were removed to determine fungal tissue burdens. Results When therapy began 1 day after challenge, posaconazole at ≥1 mg/kg significantly prolonged survival of mice compared with that of the control group and considerably reduced the fungal tissue burden over the control group. On the other hand, when treatment was started 3 days after infection, regimens of 5 and 10 mg/kg posaconazole significantly prolonged mice survival over that of the control group and appreciably diminished the fungal load compared with untreated mice. In this model, as the severity of trichosporonosis increased, higher doses of posaconazole were required to achieve equivalent activity levels. Fluconazole and amphotericin B were ineffective in preventing mice death and in significantly reducing fungal tissue burden. Posaconazole displayed potent in vivo activity against the strain tested. Conclusions Posaconazole may be a suitable option in the treatment of disseminated T. asahii infection.