In vitro and in vivo antibacterial activities of
FK037, a new parenteral
cephalosporin, were compared with those of
cefpirome,
ceftazidime and
flomoxef. The advantages of in vitro activity of
FK037 were as follows: (1) a broad-spectrum antibacterial activity, (2) the most potent activity (MIC90: 25 micrograms/ml) of the
cephalosporins tested against highly methicillin-resistant Staphylococcus aureus (H-MRSA), (3) a strong activity against Enterobacter spp. and Citrobacter freundii resistant to the
third-generation cephalosporins tested. The MICs of
FK037 for 90% of the clinical isolates tested (MIC90s) were 0.012 microgram/ml for Streptococcus pyogenes, 0.05 microgram/ml for Escherichia coli, 0.1 microgram/ml for Streptococcus pneumoniae, 0.2 microgram/ml for Haemophilus influenzae and Proteus mirabilis, 0.39 microgram/ml for Klebsiella pneumoniae, 1.56 micrograms/ml for
methicillin-sensitive S. aureus, Proteus vulgaris and Enterobacter aerogenes, 3.13 micrograms/ml for Staphylococcus epidermidis and Moraxella catarrhalis, 6.25 micrograms/ml for C. freundii, 12.5 micrograms/ml for low-level methicillin-resistant S. aureus (L-MRSA), Enterobacter cloacae and Pseudomonas aeruginosa, and 25 micrograms/ml for H-MRSA and Serratia marcescens.
FK037 was similar in potency to
cefpirome against strains except MRSA, and was superior to
ceftazidime and
flomoxef against strains except P. vulgaris and/or M. catarrhalis. The increase in MICs of
FK037 against 2 L-MRSA strains (2- or 4-fold) was smaller than that of
cefpirome and
flomoxef (16- to 64-fold) after the third serial culture in the presence of each
drug.
FK037 was highly bactericidal against S. aureus, E. coli, K. pneumoniae and P. aeruginosa at the MIC or higher.
FK037 had a potent protective activity against murine experimental systemic
infections due to a wide variety of bacteria. Its protective activity was the strongest among the
cephalosporins tested against H-MRSA and Acinetobacter calcoaceticus. Against the other strains,
FK037 was as effective as
cefpirome and similar or superior to
flomoxef and
ceftazidime though it was inferior to
ceftazidime against P. aeruginosa. Transmission electron microscopic studies revealed that
FK037 inhibited septum formation and induced thick cross walls and bacteriolysis at the division sites in MRSA after 4 h incubation.