title: In vitro and in vivo antibacterial activities of FK037, a novel parenteral broad-spectrum cephalosporin.
abstract: FK037, a new parenteral cephalosporin, is an oxime-type cephem antibiotic with a 1-hydroxyethyl-5-amino-pyrazole moiety at the 3 position. FK037 was evaluated for antimicrobial activity in vitro and in vivo. In vitro, FK037 was twofold or more active than ceftazidime, cefoperazone, cefotaxime, and ceftriaxone against Pseudomonas aeruginosa (MIC for 90% of the strains [MIC90] = 32 micrograms/ml), members of the family Enterobacteriaceae (MIC90 < or = 2 micrograms/ml), group A streptococci (MIC90 = 0.015 microgram/ml), and methicillin-sensitive or -resistant coagulase-negative staphylococci (MIC90 = 2 and 16 micrograms/ml, respectively). In addition, the activity of FK037 was equal to or greater than that of ceftazidime, cefotaxime, or ceftriaxone against Streptococcus pneumoniae (MIC90 = 0.12 microgram/ml) and methicillin-sensitive or -resistant Staphylococcus aureus (MIC90 = 2 and 16 micrograms/ml, respectively). FK037 was more active in vitro than cefepime (two- to fourfold) and cefpirome (twofold) against S. aureus. In murine systemic infection models, FK037 showed potent activity against P. aeruginosa, Escherichia coli, and methicillin-sensitive and methicillin-resistant S. aureus. FK037 was also efficacious in a mouse model of pyelonephritis caused by S. aureus or Klebsiella pneumoniae and in a mouse model of pneumococcal pneumonia caused by S. pneumoniae. Additional studies on this compound to assess its potential clinical utility are warranted.
authors.affiliation: Microbiology Research, R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869.
authors.forename: K P
authors.initials: KP
authors.lastname: Fu
authors.forename: B D
authors.initials: BD
authors.lastname: Foleno
authors.forename: S C
authors.initials: SC
authors.lastname: Lafredo
authors.forename: J M
authors.initials: JM
authors.lastname: LoCoco
authors.forename: D M
authors.initials: DM
authors.lastname: Isaacson
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004756:Enterobacteriaceae Infections / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D008297:Male; D016106:Methicillin Resistance; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011704:Pyelonephritis / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: C079769:cefoselis; D015296:Ceftizoxime; D001618:beta-Lactamases