Combination Therapy with Ibrexafungerp (formerly SCY-078), a First-in-Class Triterpenoid Inhibitor of (1 →3)-β-D-Glucan Synthesis, and Isavuconazole for Treatment of Experimental Invasive Pulmonary Aspergillosis.

Combination Therapy with Ibrexafungerp (formerly SCY-078), a First-in-Class Triterpenoid Inhibitor of (1→3)-β-D-Glucan Synthesis, and Isavuconazole for Treatment of Experimental Invasive Pulmonary Aspergillosis. Antimicrob Agents Chemother. 2020 Mar 16;: Authors: Petraitis V, Petraitiene R, Katragkou A, Maung BBW, Naing E, Kavaliauskas P, Barat S, Borroto-Esoda K, Azie N, Angulo D, Walsh TJ Abstract Ibrexafungerp (formerly SCY-078) is a semisynthetic triterpenoid and potent (1→3)-β-D-glucan synthase inhibitor. We investigated the in vitro activity, pharmacokinetics, and in vivo efficacy of ibrexafungerp (SCY) alone and in combination with anti-mould triazole isavuconazole (ISA) against invasive pulmonary aspergillosis (IPA). The combination of ibrexafungerp and isavuconazole in in vitro studies resulted in an additive and synergistic interactions against Aspergillus spp. Plasma concentration-time curves of ibrexafungerp were compatible with linear dose proportional profile. In vivo efficacy was studied in a well established persistently neutropenic NZW rabbit model of experimental IPA. Treatment groups included untreated rabbits (UC) and rabbits receiving ibrexafungerp at 2.5(SCY2.5) and 7.5(SCY7.5) mg/kg/day, isavuconazole at 40(ISA40) mg/kg/day, or combinations of SCY2.5+ISA40 and SCY7.5+ISA40. The combination of SCY+ISA produced in vitro synergistic interaction. There was significant in vivo reduction of residual fungal burd...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research