In vitro and in vivo Antibacterial Activities of FK037, a New Parenteral Cephalosporin
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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.Keywords:
Cefpirome
Citrobacter freundii
Enterobacter cloacae
Enterobacter aerogenes
Proteus vulgaris
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