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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 (AUC_24h/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 ?g/mL at 1.52 h (T_max) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome against S. equi was 0.016 ?g/mL. The ex vivo AUC_24h/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 AUC_24h/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.

SUBMITTER: Lee DH

PROVIDER: S-EPMC7566116 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Lee Dong-Ha DH Birhanu Biruk Tesfaye BT Lee Eon-Bee EB Lee Seung-Jin SJ Boby Naila N Park Yong-Soo YS Park Seung-Chun SC

Veterinary research 20201015 1

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 a ...[more]

PMID: 33059768

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Project description:Biofilm formations play an important role in Staphylococcus aureus pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to S. aureus, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and in vitro time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study S. aureus strains. The in vivo post-antibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid E max model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four S. aureus strains were 0.5 and 16 ?g/mL, respectively. The BBCs (32-64 ?g/mL) and MBECs (64-256 ?g/mL) of these study strains were much higher than their corresponding BPC values (1-2 ?g/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The best-correlated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (fT > MIC, R (2) = 96.2%) and the MBIC (fT > MBIC, R (2) = 94.7%), respectively. In addition, the AUC24h/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (R (2) = 93.1%). The values of AUC24h/MBIC for biofilm-static and 1-log10-unit biofilm-cidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for effective dosing regimens treating S. aureus biofilm-related infections.

Dataset Information

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

Publications

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

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