Activity of cefquinome against extended‐spectrum β‐lactamase‐producing Klebsiella pneumoniae in neutropenic mouse thigh model. Issue 4 (29th September 2016)

• Record Type: Journal Article
• Authors: Shan, Q.; Wang, J.
• Is Part Of: Journal of veterinary pharmacology and therapeutics. Volume 40:Issue 4(2017)
• Page Start: 392
• Page End: 397
• Publication Date: 2016-09-29
• Subjects: Veterinary pharmacology -- Periodicals; Therapeutics -- Periodicals; 636.0895105
• DOI: 10.1111/jvp.12365
• Languages: English
• ISSNs: 0140-7783

Abstract

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 (% f T > MIC) was the PK–PD index that best correlated with cefquinome efficacy ( R 2 = 86%). Using a sigmoid Emax model, the magnitudes of % f T > 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.