Beta-lactamase stability of cefpirome (HR 810), a new cephalosporin with a broad antimicrobial spectrum.

Cefpirome was highly stable to hydrolysis by various beta-lactamases, although it was hydrolyzed to some extent by R plasmid-mediated penicillinase of Richmond-Sykes type Va/b and by chromosomal cephalosporinases from Bacteroides species. The compound had a very low affinity for cephalosporinases from Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Proteus vulgaris. Cefpirome showed strong antimicrobial activity against eight beta-lactamase (cephalosporinase)-producing strains which have become resistant to broad-spectrum cephalosporins; especially against E. cloacae and C. freundii, it had the highest activity among the cephalosporins used. Its activity against ampicillin-resistant R plasmid-containing transconjugant isolates of Escherichia coli was as high as that against the recipient strain E. coli chi 1037. The inducer activity of cefpirome in S. marcescens and P. vulgaris increased dose dependently, whereas cephamycin derivatives showed high inducer activity at low concentrations. A relatively low affinity of cefpirome for beta-lactamases is considered to be one of the reasons for its high antimicrobial activity against such enzyme-producing strains. In addition, other factors such as good penetration through the outer membrane and affinity for the target sites may also be involved in the high activity of cefpirome.