Beta-lactamase inhibitory activities and synergistic effects of 5,6-cis-carbapenem antibiotics.

Twelve 5,6-cis-carbapenem antibiotics were examined for their beta-lactamase inhibitory activities, their types of inhibitions, and their synergistic activities with other beta-lactam antibiotics. All the carbapenems inhibited eight types of beta-lactamases including cephalosporinases which were insensitive to clavulanic acid and sulbactam. The sulfonyloxy ethyl carbapenems were the most active inhibitors; they inhibited all beta-lactamases in a progressive fashion, whereas some of the hydroxyl compounds exerted non-progressive inhibition against several beta-lactamases such as those of Escherichia coli TN713 and Proteus vulgaris GN4413. Several carbapenems were inactivated by the beta-lactamases of Citrobacter freundii GN1706, P. vulgaris GN4413, E. coli TN713, and Klebsiella pneumoniae TN1698. Most of the carbapenems potentiated the antibacterial activities of ampicillin and cefotiam against beta-lactamase-producing bacteria.