BETA-LACTAMASE HYDROLYSIS OF CEPHALOSPORIN 3'-QUINOLONE ESTERS, CARBAMATES, AND TERTIARY-AMINES

The beta-lactam hydrolysis of five cephalosporin 3'-quinolones (dual-a ction cephalosporins) by three gramnegative beta-lactamases was examin ed. The dual-action cephalosporins tested were the ester Ro 23-9424; t he carbamates Ro 25-2016, Ro 25-4095, and Ro 25-4835; and the tertiary amine Ro 25-0534. Also tested were cephalosporins with similar side c hains (cefotaxime, desacetylcefotaxime, cephalothin, cephacetrile, and Ro 09-1227 [SR 0124]) and standard beta-lactams (penicillin G, cephal oridine). The beta-lactamases used were the plasmid-mediated TEM-1 and TEM-3 enzymes and the chromosomal AmpC. The cephacetrile-related comp ounds Ro 25-4095 and Ro 25-4835 were hydrolyzed by all three beta-lact amases with catalytic efficiencies (relative to penicillin G) ranging from similar to 5 (TEM-1, AmpC) to similar to 25 (TEM-3). The cephalot hin-related Ro 25-2016 was also hydrolyzed by all three beta-lactamase s, particularly the AmpC enzyme (relative catalytic efficiency, 110). The cefotaxime-related compounds Ro 25-0534 and Ro 23-9424 were hydrol yzed to any significant extent only by the TEM-3 enzyme (relative cata lytic efficiencies, 1.2 and 4.7, respectively).