Diastereomeric 7-ureidoacetyl cephalosporins. III. Contribution of D- and L-isomers to the growth inhibiting activities of 7.ALPHA.-H and 7.ALPHA.-OCH3 derivatives for gram-positive and gram-negative bacteria.

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Abstract
A series of 7.beta.-ureidoacetyl, 7.alpha.-H and 7.alpha.-OCH3 cephalosporin antibiotics showed broad-spectrum antibacterial activity in vitro. In the 7.alpha.-H but not in the 7.alpha.-OCH3 series, contrary to experience in the antibiotic field, the L-isomers were substantially more active than the D-isomers both in vitro and in vivo particularly, but not exclusively, against Enterobacteriaceae that produce cephalosporinases. Enhanced resistance to and inhibition of .beta.-lactamase(s) appeared to be responsible for this effect. Studies in vitro specifically with 7.beta.-thienylureidoacetyl derivatives showed that D-isomers interacted with L-isomers in the 7.alpha.-OCH3 series in a synergistic manner against "cephalosporinase-type" enzyme producers while isomers in the 7.alpha.-H series did not. Examples were presented in which this favorable event resulted in improved efficacy of the racemic mixture over the pure D- or L-isomer alone in appropriate experimental infections.