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. 2015 Jun 17:6:588.
doi: 10.3389/fmicb.2015.00588. eCollection 2015.

Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle

Ijaz Ahmad  1 , Haihong Hao  2 , Lingli Huang  3 , Pascal Sanders  4 , Xu Wang  2 , Dongmei Chen  5 , Yanfei Tao  5 , Shuyu Xie  3 , Kuang Xiuhua  2 , Juan Li  2 , Wan Dan  2 , Zonghui Yuan  6
Affiliations

Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle

Ijaz Ahmad et al. Front Microbiol. .

Abstract

Cefquinome is a fourth generation cephalosporin with antimicrobial activity against gram negative and gram positive bacterial species, including Staphylococcus aureus. The aim of our study was to observe the ex-vivo activity of cefquinome against Staphylococcus aureus strains by using bovine serum from intravenously treated cattle. Cefquinome kinetics were measured by liquid chromatography and UV detection. In vitro post antibiotic effects (PAEs) and mutant prevention concentrations were determined with S. aureus strain ATCC 12598. Cefquinome exhibited time-dependent killing and produced in vitro PAEs increasing with concentration and time of exposure. A pharmacokinetic-pharmacodynamic model was established to simulate the efficacy of cefquinome for different dosage regimens. A dosage of 2 mg/kg every 12 h for 3 days was expected to reach a bactericidal activity against S. aureus in case of septicemia.

Keywords: PK/PD; Staphylococcus aureus; cattle; cefquinome; septicemia.

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Figures

Figure 1
Figure 1
Semi-logarithmic plot of mean serum concentration after intra venous administration of cefquinome (1 mg/kg) in cattle (n = 6). Two compartment method (Winonlin software) were used to observe the concentration-time curve.
Figure 2
Figure 2
In vitro antibacterial activity of cefquinome against Staphylococcus aureus in MH broth. The figures show that cefquinome exhibit time dependent activity when the concentration increases.
Figure 3
Figure 3
Ex-vivo antibacterial activity of cefquinome in serum of cattle against staphylococcus aureus after intravenous administration (n = 6). The concentration of cefquinome in serum at different time interval shows its effect on staphylococcus aureus.
Figure 4
Figure 4
Simulate the effect of different doses (0.5, 1, 2.5, 5, 7.5 mg/kg). The effect of different doses were observed on bacteria and its elimination.
Figure 5
Figure 5
Simulate different dosage regimen (1 mg/kg every 12 h, 1 mg/kg every 24 h, and 2 mg/kg every 24 h, 2 mg/kg every 12 h, and 5 mg/kg every 24 h). The different doses were simulated for different intervals of time to find the efficient dose and dose intervals
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