Cephamycins, a New Family of β-Lactam Antibiotics. III. In Vitro Studies

Cephamycins A, B, and C are naturally produced cephalosporin-type antibiotics. Although A and B were found to be more active than C against gram-positive organisms, they were not so active against such strains as are cephalosporin C or the semisynthetic antibiotics cephaloridine and cephalothin. Against gram-negative organisms, cephamycin C was more active than A or B and, in general, was as active as the cephalosporins. In addition, cephamycin C was active in vitro against clinically isolated strains resistant to the cephalosporins, such as Proteus, Providencia, and Escherichia coli. The in vitro antibacterial activity of cephamycin C, cephalothin, and cephaloridine is primarily bactericidal. A 10,000-fold increase in inoculum of a strain of Proteus mirabilis resulted in 200-fold or greater increases in minimal inhibitory and minimal bactericidal end points of cephalothin and cephaloridine, but only 10- and 16-fold increases, respectively, for cephamycin C. After 15 passages through antibiotic-containing broths, during which time a culture of E. coli showed an increase in minimal inhibitory concentrations of streptomycin of >1,000-fold, end points for cephamycin C increased 4-fold, for cephalothin, 1.5-to 6-fold, and for cephaloridine, 128-fold.