title: In vitro antibacterial activity of FK041, a new orally active cephalosporin.
abstract: The in vitro activity of FK041, a new orally active cephem antibiotic, against a wide variety of clinical isolates of bacteria was investigated and compared with those of cefdinir (CFDN) and cefditoren (CDTR). FK041 exhibited broad spectrum activity against reference strains of Gram-positive and Gram-negative aerobes and anaerobes. FK041 was active against clinical isolates of Gram-positive organisms except Enterococcus faecalis with MIC90s less than 1.56 microg/ml. FK041 was more active than CFDN and CDTR against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae and was comparable to CFDN and CDTR against Streptococcus pyogenes and Streptococcus pneumoniae. FK041 had no activity against methicillin-resistant staphylococci, like CFDN and CDTR. FK041 showed moderate activity against penicillin-resistant S. pneumoniae with an MIC range of 0.05 approximately 3.13 microg/ml, and was superior to CFDN but inferior to CDTR. Against clinical isolates of many Gram-negative organisms such as Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, FK041 had good activity comparable or superior to those of CFDN and CDTR. However, it was inferior to CDTR in activity against Moraxella catarrhalis, Haemophilus influenzae, Morganella morganii, and Serratia marcescens, and was inactive against Pseudomonas aeruginosa. With FK041 a small difference between MIC and MBC 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 2beta-lactamase hydrolysis but was unstable to group 1beta-lactamase hydrolysis. The stability of FK041 to these enzymes was similar to those of CFDN and CDTR. FK041 showed high affinity for the main penicillin-binding proteins (PBPs) of S. aureus (PBP 3, 2, and 1) and E. coli (PBP 3, 4, lbs, 2, and 1a).
authors.affiliation: Klinge Pharma GmbH, Munich, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Hatano
authors.forename: Y
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Tawara
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Kawabata
authors.forename: H
authors.initials: H
authors.lastname: Takasugi
authors.forename: F
authors.initials: F
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Kuwahara
mesh_terms: D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000382:microbiology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism; D018550:Cephalosporin Resistance; D002510:Cephalosporinase / Q000378:metabolism; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006602:Hexosyltransferases; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; C114137:FK 041; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D002510:Cephalosporinase