Comparative activity of cefotetan on Escherichia coli K12 possessing plasmid-mediated beta-lactamases

The antibacterial activity of cefotetan, a new cephamycin, was compared with that of cephalothin, cefoxitin, cefamandole, cefoperazone and cefotaxime on 12 substrains of Escherichia coli K12 BM13 harbouring single and multi-copy plasmids coding for plasmid-mediated beta-lactamases TEM, SHVI, OXA-I and OXA-III. The 99% inhibitory concentrations (IC99) for the recipient strain were increased in proportion to the enzyme activity in the case of cefamandole and cefoperazone. In contrast, the activity of cefoxitin, cefotaxime and cefotetan was not significantly modified. Since these enzymes are responsible for the resistance of Enterobacteriaceae in the great majority of clinical isolates, cefotetan can be expected to be fully active against strains producing them. Cefotetan was not hydrolysed by chromosomal cephalosporinase and it was active against Enterobacter, Citrobacter and Morganella strains producing a low level of enzyme but hyperproducing variants were highly resistant to cefotetan.