620. Oral β-Lactamase Therapies Prevent Microbiome Damage and Attenuate Antibiotic Resistance From IV and Oral Antibiotics in Large Animal Models of Antibiotic-Mediated Gut Dysbiosis

摘要

BackgroundAntibiotics can damage the gut microbiome leading to overgrowth of pathogens and provide selective pressure for emergence of antibiotic resistance. SYN-004 (ribaxamase) is a clinical-stage β-lactamase formulated for oral delivery intended to degrade certain β-lactam antibiotics in the GI tract to preserve the gut microbiome. Ribaxamase was evaluated in a phase 2b clinical study that met its primary endpoint of significantly reducing C. difficile infection in patients treated with IV ceftriaxone and demonstrated protection of the gut microbiome with reduced emergence of antibiotic resistance. Ribaxamase is intended for use with IV penicillins and cephalosporins, but does not degrade carbapenems. Β-lactamase-mediated microbiome protection was expanded to include oral and carbapenem antibiotics.