Pharmacokinetic and pharmacodynamic integration for optimal dosage of cefquinome against Streptococcus equi subsp. equi in foals

Abstract

Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefquinome concentrations were determined by high-performance liquid chromatography. The in vitro and ex vivo antibacterial activity were determined from minimum inhibitory concentrations (MIC) and bacterial killing curves. The optimal dosage was calculated from the integration of pharmacokinetic parameters and area under the curve (AUC24h/MIC) values. Total body clearance and volume of distribution of cefquinome after intravenous administration were 0.06 L/h/kg and 0.09 L/kg, respectively. Following intramuscular administration, a maximum concentration of 0.73 μg/mL at 1.52 h (Tmax) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome against S. equi was 0.016 μg/mL. The ex vivo AUC24h/MIC values representing bacteriostatic, and bactericidal activity were 113.11, and 143.14 h, respectively. Whereas the %T > MIC for bactericidal activity was 153.34%. In conclusion, based on AUC24h/MIC values and pharmacokinetic parameters, cefquinome when administered by intramuscularly at a dosage of 0.53 mg/kg every 24 h, would be effective against infection caused by S. equi in foals. Further studies may be necessary to confirm its therapeutic efficacy in a clinical environment.

Determination of Susceptibility Breakpoint for Cefquinome against Streptococcus suis in Pigs

“…As the concentration increased in serum, the bacterial counts decreased after 24 h of incubation, indicating that the antibacterial activity is concentration-related under ex vivo conditions. In addition, the different parameters based on the values of T > MIC and bacterial counts (log 10 CFU/mL) cannot be acquired using ex vivo PK/PD integration, and AUC/MIC is also used for describing the character of antibacterial activity of cefquinome [ 19 ]. For these reasons, AUC/MIC was regarded as the most appropriate PK/PD index to describe the antibacterial activity of cefquinome in serum.…”

“…The PK/PD model is recognized to evaluate and optimize the dose regimen and guide clinical treatment. There are many previous studies investigating the dose of cefquinome against a specific bacterium [ 19 , 20 , 21 ]. From the manuscript, the ECOFF, CO PD and CO CL were determined as 1 μg/mL, 0.06 μg/mL and 0.5 μg/mL, respectively.…”

Equine antimicrobial therapy: Current and past issues facing practitioners

“…An example of dosage optimization of an antimicrobial in horses is a study evaluating both pharmacokinetics and pharmacodynamics of cefquinome in foals for potential treatment of S . equi subsp equi (Lee et al, 2020). The authors studied the in vitro and ex vivo antibacterial activity and used this along with AUC/MIC ratio and bioavailability of the antibiotic to determine the optimal dosing regimen.…”

Ceftiofur use and antimicrobial stewardship in the horse

“…Cefquinome (Cobactan IV, MSD Animal Health) is approved for use in Europe for the treatment of equine respiratory disease caused by S. zooepidemicus (1 mg/kg, every 24 h) and severe bacterial infections with a high risk of septicaemia in foals in which E. coli is involved (1 mg/kg, every 12 h). Cefquinome pharmacokinetics in older foals (6 months to 1 year old) have also been investigated 106 . In the study, 1 mg/kg of cefquinome was administered iv and im.…”