Activity of cefquinome against extended-spectrum β-lactamase-producing Klebsiella pneumoniae in neutropenic mouse thigh model.
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 Emaxmodel, the magnitudes of %fT > MIC producing net bacterial stasis, a 1-log10kill and a 2-log10kill 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.
Key Laboratory of Tropical and Subtropical Fishery Resource Application and Cultivation of Ministry of Agriculture, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China.
Q
Q
Shan
Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, China.
J
J
Wang
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002417:Cattle; D002511:Cephalosporins / Q000494:pharmacology*; D004347:Drug Interactions; D007711:Klebsiella pneumoniae / Q000378:metabolism*; D051379:Mice; D008826:Microbial Sensitivity Tests; D012756:Sheep; D013552:Swine; D053719:Tandem Mass Spectrometry; D001618:beta-Lactamases / Q000187:drug effects* / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D001618:beta-Lactamases; C068212:cefquinome