The antibacterial activity of BK-218 was similar to that of cefamandole when it was tested against several laboratory strains. The inhibiting effect of BK-218 was greater than that of cephalexin and cefoxitin on penicillin-binding proteins of Escherichia col HB101. This result was in close correlation with the relative inhibition of radiolabeled glucosamine incorporation (greatest with BK-218) and with the lytic effect (most intensive with BK-218). BK-218 proved to be a good inhibitor for all five of the ,-lactamases that were investigated, although two enzymes (Enterobacter cloacae P99 and Pseudomonas aeruginosa Cilote) hydrolyzed it to some extent.Cephalexin (4), cefadroxil (7), cefaclor (4,21), cefroxadine (34), and cefatrizine (22) (Fig. 1.), is a new oral cephalosporin.It is well-known that beta-lactam antibiotics first bind to their targets, the so-called penicillin-binding proteins (PBPs). The inhibition of these enzymes suspends peptidoglycan synthesis, and as a consequence the autolytic enzymes are triggered with a mechanism whose details are not completely understood (16).The purpose of this study was to report the results of preliminary investigations concerning the in vitro activity of BK-218 against a limited number of gram-positive and gramnegative bacteria. The MICs of BK-218 were compared with those of other parenteral (cefuroxime, cefamandole, and cefoxitin) and oral (cephalexin) antibiotics.The in vitro effect on the targets was measured by (i) affinity to PBPs, (ii) incorporation of labeled glucosamine into the cell wall of Escherichia coli, and (iii) release of labeled glucosamine-containing fragments from prelabeled cell wall of E. coli to assess the lysis capability of BK-218.