Stability of cefotetan to Gram-negative beta-lactamases

The bacteriostatic and bactericidal properties of cefotetan, a new 7-methoxy-cephalosporin have been investigated against 200 strains of Gram-positive and Gram-negative organisms in comparison with cefoxitin, ceftriaxone and cefazolin. The most striking feature of antimicrobial activity of cefotetan is its effectiveness against strains belonging to the genera Klebsiella, Enterobacter and Serratia, usually resistant to many β-lactam antibiotics. Crude preparations of 12 types of β-lactamases, both plasmid- and chromosomally-mediated, were used to determine the susceptibility of cefotetan to hydrolysis. The results, compared with those of cefoxitin, ceftizoxime, ceftriaxone and ceftazidime in addition to the standard of cephaloridine, indicate that cefotetan, like other methoxy-cephalosporins, is highly stable. The penetrability studies demonstrate that, using Escherichia coli UB 1005 and its mutants, cefotetan behaves like ceftazidime, ceftizoxime and cefoxitin, whilst using Pseudomonas aeruginosa 1771 and its mutant, the penetrability of cefotetan was higher than that of other cephalosporins under consideration.