Efficacy of the Investigational Echinocandin ASP9726 in a Guinea Pig Model of Invasive Pulmonary Aspergillosis.

Efficacy of the Investigational Echinocandin ASP9726 in a Guinea Pig Model of Invasive Pulmonary Aspergillosis. Antimicrob Agents Chemother. 2015 Mar 9; Authors: Wiederhold NP, Najvar LK, Matsumoto S, Bocanegra RA, Herrera ML, Wickes BL, Kirkpatrick WR, Patterson TF Abstract ASP9726 is an investigational echinocandin with in vitro activity against Aspergillus species. We evaluated the pharmacokinetics and efficacy of this agent in a established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, & 10 mg/kg/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated with A. fumigatus AF293, and treatment with ASP9726 (2.5, 5, & 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) were administered for 8 days. Changes in fungal burden were measured by colony-forming units and quantitative PCR within the lungs, as well as serum (1→3)-β-D-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR, (1→3)-β-D-glucan and galactomannan, but only voriconazol...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research