title: Pharmacodynamics of cefquinome in a neutropenic mouse thigh model of Staphylococcus aureus infection.
abstract: Cefquinome is a cephalosporin with broad-spectrum antibacterial activity, including activity against Staphylococcus aureus. The objective of our study was to examine the in vivo activity of cefquinome against S. aureus strains by using a neutropenic mouse thigh infection model. Cefquinome kinetics and protein binding in infected neutropenic mice were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In vivo postantibiotic effects (PAEs) were determined after a dose of 100 mg/kg of body weight in mice infected with S. aureus strain ATCC 29213. The animals were treated by subcutaneous injection of cefquinome at doses of 2.5 to 320 mg/kg of body weight per day divided into 1, 2, 3, 6, or 12 doses over 24 h. Cefquinome exhibited time-dependent killing and produced in vivo PAEs at 2.9 h. The percentage of time that serum concentrations were above the MIC (%T>MIC) was the pharmacokinetic-pharmacodynamic (PK-PD) index that best described the efficacy of cefquinome. Subsequently, we employed a similar dosing strategy by using increasing total cefquinome doses that increased 4-fold and were administered every 4 h to treat animals infected with six additional S. aureus isolates. A sigmoid maximum effect (Emax) model was used to estimate the magnitudes of the ratios of the %T that the free-drug serum concentration exceeded the MIC (%T>fMIC) associated with net bacterial stasis, a 0.5-log10 CFU reduction from baseline, and a 1-log10 CFU reduction from baseline; the respective values were 30.28 to 36.84%, 34.38 to 46.70%, and 43.50 to 54.01%. The clear PAEs and potent bactericidal activity make cefquinome an attractive option for the treatment of infections caused by S. aureus.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shan
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
authors.forename: Huanzhong
authors.initials: H
authors.lastname: Ding
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
authors.forename: Chaoping
authors.initials: C
authors.lastname: Liang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China zlzeng@scau.edu.cn.
authors.forename: Zhenling
authors.initials: Z
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002511:Cephalosporins / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009503:Neutropenia; D013047:Specific Pathogen-Free Organisms; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*; D053719:Tandem Mass Spectrometry; D013848:Thigh / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C068212:cefquinome