Antimicrobial Activity of Cefmenoxime (SCE-1365)

Abstract

The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was compared with those of cefazolin, cefoxitin, and cefamandole against a broad spectrum of 486 organisms and with that of cefotaxime against 114 organisms. Cefmenoxime and cefotaxime exhibited nearly equivalent activities against those organisms tested and were the most active of these cephalosporins against all aerobic and facultative organisms except Staphylococcus aureus . The minimum inhibitory concentration (MIC) of cefmenoxime required to inhibit at least 90% of strains tested (MIC 90 ) ranged from 0.06 to 8 μg/ml for the Enterobacteriaceae . The MIC 90 s for gram-positive cocci were 0.015 and ≤0.008 μg/ml for Streptococcus pneumoniae and Streptococcus pyogenes , respectively, and 2 μg/ml for S. aureus . Group D streptococci were less susceptible. Cefmenoxime was very active against Haemophilus influenzae, Neisseria gonorrhoeae , and Neisseria meningitidis with MIC 90 s ranging from ≤0.008 to 0.25 μg/ml. Cefmenoxime, at a concentration of 16 μg/ml, inhibited 78% and 73% of Pseudomonas aeruginosa and Acinetobacter spp., respectively. MICs for anaerobes ranged from 0.5 to >128 μg/ml with good activity against the gram-positive organisms. In addition, cefmenoxime activity was bactericidal and only slightly affected by differences in inoculum size. The combination of cefmenoxime and gentamicin was synergistic against 80% of the Enterobacteriaceae and 100% of P. aeruginosa strains tested. Development of resistance to cefmenoxime was slow or absent for organisms with low initial MICs but more rapid for those with higher initial MICs. Cefmenoxime exhibited good protective activity in mice infected with Escherichia coli, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris , or S. aureus but was less effective against P. aeruginosa .