Diastereomeric 7-ureidoacetyl cephalosporins. III. Contribution of D- and L-isomers to the growth inhibiting activities of 7alpha-H and 7alpha-OCH3 derivatives for gram-positive and gram-negative bacteria.
A series of 7beta-ureidoacetyl, 7alpha-H and 7alpha-OCH3 cephalosporin antibiotics have shown broad-spectrum antibacterial activity in vitro. In the 7alpha-H but not in the 7alpha-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 potent chromosomal cephalosporinases. Enhanced resistance to and inhibition of beta-lactamase (s) appeared to be responsible for this effect. Studies in vitro specifically with 7beta-thienylureidoacetyl derivatives showed that D-isomers interacted with L-isomers in the 7alpha-OCH3 series in a synergistic manner against "cephalosporinase-type" enzyme producers while isomers in the 7alpha-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.
D000818:Animals; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D001424:Bacterial Infections / Q000188:drug therapy; D002510:Cephalosporinase / Q000302:isolation & purification; D002511:Cephalosporins / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006868:Hydrolysis; D007700:Kinetics; D051379:Mice; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002511:Cephalosporins; D002510:Cephalosporinase