In-vitro antibacterial activity of cefotetan

The in-vitro activity of cefotetan, a recently developed cephamycin, was investigated under various experimental conditions. The compound showed moderate activity against Staphylococcus aureus and Streptococcus pyogenes, no activity against Pseudomonas aeruginosa and Streptococcus faecalis, but a high activity against Enterobacteriaceae, including beta-lactamase-producing strains. Haemophilus influenzae also was fairly susceptible. The MBC was usually equal to or two- or fourfold higher than MIC. Medium composition, pH and inoculum size had minimal influence on its activity. About 50% of recent clinical isolates of Bacteroides fragilis were susceptible to cefotetan, but some were highly resistant. Killing curves of cefotetan against different bacterial strains indicated that it was rapidly bactericidal at concentrations equal to MIC or two- to fourfold higher. However, some strains showed regrowth after initial inhibition. Combination of cefotetan with aminoglycosides, or with cefazolin, cefotaxime, moxalactam or piperacillin resulted either in synergy, addition or indifference according to the bacterial strain and the nature of the combination. Antagonism was never observed. Human serum protein binding varied from 75 to 86% according to the assay method. Binding with horse serum protein was about 28%.