Interaction of Ro 17-2301 (AMA-1080) with beta-lactamases.

Against a variety of beta-lactamases tested, mostly of chromosomal origin, Ro 17-2301 (AMA-1080) proved to be more stable than the new cephalosporins and thus resembles aztreonam. Against the beta-lactamases from Klebsiella oxytoca and Pseudomonas vulgaris, however, Ro 17-2301 proved to be much more stable than aztreonam. Enzymatic hydrolysis, performed with the K. oxytoca beta-lactamase, yielded a single compound, viz. the microbiologically inactive, ring-opened structure. Ro 17-2301 is a potent and progressive inhibitor of cephalosporinases found, e.g., in Enterobacter cloacae and other gram-negative organisms. The IC50 and Ki values, however, showed that the affinity for these enzymes is lower than that of aztreonam.