PBP BINDING AND PERIPLASMIC CONCENTRATION AS DETERMINANTS OF THE ANTIBACTERIAL ACTIVITIES OF 3 NEW ORAL CEPHALOSPORINS IN ESCHERICHIA-COLI

The antibacterial activities of cefetamet, cefixime and cefuroxime wer e investigated in Escherichia coli with regard to their penetration ra tes through the outer membrane and their affinities for PBPs in Escher ichia coli The permeability coefficient of cefetamet was measured in E . coli C600 carrying a pUC18 plasmid derivative, in which the gene of a transferable cephamycinase (CMY-2) was cloned, whereas diffusion of cefixime and cefuroxime was measured in E. coli C600 harbouring the OX A-1 beta-lactamase gene. It was found that cefetamet penetrated 5 and 9 times faster than cefixime and cefuroxime, respectively. The correla tion between antibacterial activities and PBP affinities was studied i n E. coli C600 not producing beta-lactamases. In this strain, cefetame t and cefixime shared the same inhibitory activity (MIC = 1 mu g/ml fo r both antibiotics) and the same affinity for PBP 3 (ID50 = 0.25 mu g/ ml). Cefuroxime had a lower inhibitory activity (MIC = 4 mu g/ml) and a lower affinity for PBP 3 (ID50 = 0.5 mu g/ml). Cefixime and cefuroxi me had 20 and 10 times higher affinity, respectively, than cefetamet f or PBP Is. It was concluded that the superior PBP affinity of cefixime can counterbalance the better penetration of cefetamet through the ou ter membrane, whilst differences in either permeability or PBP affinit y seem sufficient to explain the lower antibacterial activity of cefur oxime compared to cefixime, which might well be related to the poor st ability of the cefuroxime molecule.