In vitro antibacterial activity of FK041, a new orally active cephalosporin

The in vitro activity of FK041, a new orally active cephem antibiotic, agai nst a wide variety of clinical isolates of bacteria was investigated and co mpared with those of cefdinir (CFDN) and cefditoren (CDTR). FK041 exhibited broad spectrum activity against reference strains of Gram-positive and Gra m-negative aerobes and anaerobes. FK041 was active against clinical isolate s of Gram-positive organisms except Enterococcus faecalis with MIC(90)s les s than 1.56 mu g/ml. FK041 was more active than CFDN and CDTR against Staph ylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae and was comparable to CFDN and CDTR against Streptococcus pyogenes and Stre ptococcus pneumoniae. FK041 had no activity against methicillin-resistant s taphylococci, like CFDN and CDTR. FK041 showed moderate activity against pe nicillin-resistant S. pneumoniae with an MIC range of 0.05 similar to 3.13 mu g/ml, and was superior to CFDN but inferior to CDTR. Against clinical is olates of many Gram-negative organisms such as Neisseria gonorrhoeae, Esche richia coli, Klebsiella pneumoniae, and Proteus mirabilis, FK041 had good a ctivity comparable or superior to those of CFDN and CDTR. However, it was i nferior to CDTR in activity against Moraxella catarrhalis, Haemophilus infl uenzae, Morganella morganii, and Serratia marcescens, and was inactive agai nst Pseudomonas aeruginosa. With FK041 a small difference between MIC and M BC against S. aureus, E. coli, K. pneumoniae, and H. influenzae was found, indicating that its action is bactericidal against these species. FK041 was stable to group 2 beta-lactamase hydrolysis but was unstable to group 1 be ta-lactamase hydrolysis. The stability of FK041 to these enzymes was simila r to those of CFDN and CDTR. FK041 showed high affinity for the main penici llin-binding proteins (PBPs) of S. aureus (PBP 3, 2, and 1) and E. coli (PB P 3, 4, lbs, 2, and 1a).