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

Abstract

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.

Cephamycins, a New Family of β-Lactam Antibiotics: Antibacterial Activity and Resistance to β-Lactamase Degradation

“…The advantage in efficacy in vivo and (12). (C) Calculated from data in Table 4. in vitro of cephamycin C over the cephalosporins has been demonstrated with this group of Proteus species (17,18). Our failure to demonstrate any significant degree of ,-lactamase degradation of the cephalosporins by these resistant cultures led us to reexamine our approach to the problem and to evaluate the possible role of an inducible B-lactamase as a mechanism of resistance.…”

“…The disc susceptibility data for the 466 clinical isolates show that cephamycin C has a spectrum of activity against gram-negative bacteria very similar to that displayed by the commercial synthetic cephalosporins cephaloridine and cephalothin (Table 1). Cephamycin C is essentially inactive against gram-positive organisms (18). However, as will be demonstrated below, more gram-negative strains which are resistant to cephalosporinlike antibiotics in general or which produce ,Blactamase are susceptible to cephamycin C than to cephaloridine or cephalothin.…”

Effects of Rate of Infusion and Probenecid on Serum Levels, Renal Excretion, and Tolerance of Intravenous Doses of Cefoxitin in Humans: Comparison with Cephalothin

“…Cephamycin C is active against bacterial species resistant to cephalothin and cephaloridine, such as Proteus vulgaris (13). In animals, cephamycin C is therapeutically effective against systemic infections; high doses failed to reveal gross evidence of nephrotoxicity (12).…”

Cefoxitin, a Semisynthetic Cephamycin Antibiotic: Susceptibility Studies

“…Recently, the discovery of a new family of antibiotics, the cephamycins, has been reported (1,3,(6)(7)(8)(9)11). These 7-methoxylated cephalosporins possess marked resistance to the action of ,@-lactamases from gram-positive and gramnegative organisms (10).…”