Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin.
Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded beta-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing.
Limbert
M
M
Hoechst AG, Pharma Research, Frankfurt/Main, Federal Republic of Germany.
Isert
D
D
Klesel
N
N
Markus
A
A
Seeger
K
K
Seibert
G
G
Schrinner
E
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D001421:Bacteria, Anaerobic / Q000187:drug effects; D001426:Bacterial Proteins; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002417:Cattle; D002511:Cephalosporins / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D003470:Culture Media; D004285:Dogs; D004795:Enzyme Stability; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006602:Hexosyltransferases; D006736:Horses; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D018805:Sepsis / Q000188:drug therapy; D013552:Swine; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001798:Blood Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D003470:Culture Media; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; C068212:cefquinome