In vitro evaluation of U63196-E (AC-1370): antimicrobial activity, beta-lactamase stability, and beta-lactamase inhibition

Abstract

Upjohn compound U63196 -E (formerly AC-1370) is a new semisynthetic cephalosporin with a broad spectrum of antimicrobial activity that includes Pseudomonas aeruginosa (minimum inhibitory concentration, 8.0 micrograms/ml), nearly all members of the Enterobacteriaceae, and most gram-positive cocci except enterococci and staphylococci resistant to to methicillin. The compound was stable to most commonly isolated beta-lactamases, especially TEM-1, TEM-2, and P-99; the highest rates of hydrolysis of U63196 -E were by PSE enzymes (23.4-92.5% of the relative hydrolysis rate of cephaloridine). Compared to eight other beta-lactams, U63196 -E was a poor inhibitor of beta-lactamases.