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: Jing Wang, Qi Shan, Huanzhong Ding, Chaoping Liang, Zhenling Zeng
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 58 Issue 6 Pg. 3008-12 (Jun 2014) ISSN: 1098-6596 [Electronic] United States
• PMID: 24614373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Cephalosporins
• cefquinome

Topics

• Animals
• Anti-Bacterial Agents (pharmacokinetics)
• Area Under Curve
• Cephalosporins (pharmacokinetics)
• Disease Models, Animal
• Female
• Mice
• Mice, Inbred ICR
• Microbial Sensitivity Tests
• Neutropenia
• Specific Pathogen-Free Organisms
• Staphylococcal Infections (drug therapy)
• Staphylococcus aureus (drug effects)
• Tandem Mass Spectrometry
• Thigh (microbiology)