Some biological properties of cephalosporin C and a derivative

Some biological properties of cephalosporin C and of a pyridinium derivative, "cephalosporin C(A) (pyridine)," were examined. Staphylococci, both penicillinase-producing and non-penicillinase-producing, and some other bacteria tested, were inhibited by 60 to 125 mug cephalosporin C/ml., and 5 to 20 mug cephalosporin C(A) (pyridine)/ml. The ratio of the activity of the two antibiotics varied for different organisms. Resistance developed slowly on repeated subculture of penicillinase-producing staphylococci in presence of either antibiotic. The minimum inhibitory concentration of cephalosporin C(A) (pyridine) upon penicillinase-producing staphylococci increased 4 to 8-fold with a 500-fold increase in inoculum size; with cephalosporin C there was a 2-fold increase. Their activity was not reduced by serum. Both substances were non-toxic. They were excreted quantitatively in the urine when given intravenously or subcutaneously to mice. After oral administration less than 5% of the dose was excreted. Cephalosporin C(A) (pyridine) was about 8 times more active than cephalosporin C in protecting mice from an experimental streptococcal infection, nine doses of 6.25 mg/kg affording complete protection.