Activity of cefquinome against extended-spectrum β-lactamase-producing Klebsiella pneumoniae in neutropenic mouse thigh model.

Abstract

Increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) is of clinical concern. The objective of our study was to examine the in vivo activity of cefquinome against ESBL-producing K. pneumoniae strain 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). Dose-fractionation studies over a 24-h dose range of 2.5-320 mg/kg were administered every 3, 6, 12, or 24 h. The percentage of the dosing interval that the free-drug serum levels exceed the MIC (%fT > MIC) was the PK-PD index that best correlated with cefquinome efficacy (R2  = 86%). Using a sigmoid Emax model, the magnitudes of %fT > MIC producing net bacterial stasis, a 1-log10 kill and a 2-log10 kill over 24 h, were estimated to be 20.07%, 29.57%, and 55.12%, respectively. These studies suggest that optimal cefquinome PK/PD targets are not achieved in pigs, sheep, and cattle at current recommended doses (1˜2 mg/kg). Further studies with higher doses in the target species are needed to ensure therapeutic concentration, if cefquinome is used for treatment of K. pneumoniae infection.

• Authors: Q Shan, J Wang
• Journal: Journal of veterinary pharmacology and therapeutics (J Vet Pharmacol Ther) Vol. 40 Issue 4 Pg. 392-397 (Aug 2017) ISSN: 1365-2885 [Electronic] England
• PMID: 27682189 (Publication Type: Journal Article)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Anti-Bacterial Agents
• Cephalosporins
• beta-Lactamases
• cefquinome

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Cattle
• Cephalosporins (pharmacology)
• Drug Interactions
• Klebsiella pneumoniae (metabolism)
• Mice
• Microbial Sensitivity Tests
• Sheep
• Swine
• Tandem Mass Spectrometry
• beta-Lactamases (drug effects, metabolism)