Therapeutic potential of Fosmanogepix (APX001) for intra-abdominal candidiasis: from lesion penetration to efficacy in a mouse model.

Therapeutic potential of Fosmanogepix (APX001) for intra-abdominal candidiasis: from lesion penetration to efficacy in a mouse model. Antimicrob Agents Chemother. 2021 Jan 19;: Authors: Lee A, Wang N, Carter CL, Zimmerman M, Dartois V, Shaw KJ, Perlin DS, Zhao Y Abstract Intra-abdominal candidiasis (IAC) is one of the most common yet underappreciated form of invasive candidiasis. IAC is difficult to treat, and therapeutic failure and drug resistant breakthrough infections are common in some institutions despite the use of echinocandins as first line agents. Fosmanogepix (FMGX, formerly APX001) is a first-in-class antifungal prodrug that can be administered both intravenously and orally. FMGX is currently in Phase 2 clinical development for the treatment of life-threatening invasive fungal infections. To explore the pharmacological property and therapeutic potential of FMGX for IAC, we evaluated both drug penetration and efficacy of the active moiety manogepix (MGX, formerly APX001A) in infected liver tissues in a clinically relevant IAC mouse model due to C. albicans Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed absolute drug quantitation were employed to evaluate drug penetration into liver abscess lesions both spatially and quantitatively. The partitioning of MGX into lesions occurred slowly after a single dose; however robust accumulation in the l...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research