Pharmacokinetic-pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses.
Monte Carlo simulations
PK/PD cutoff
antimicrobial susceptibility testing
benzylpenicillin
horse
population pharmacokinetics
probability of target attainment
Journal
Frontiers in microbiology
ISSN: 1664-302X
Titre abrégé: Front Microbiol
Pays: Switzerland
ID NLM: 101548977
Informations de publication
Date de publication:
2023
2023
Historique:
received:
25
08
2023
accepted:
02
10
2023
medline:
13
11
2023
pubmed:
13
11
2023
entrez:
13
11
2023
Statut:
epublish
Résumé
The aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses. A population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations. A 3-compartment disposition model was selected. For each of these formulations, the PK/PD cutoff was estimated for different dosage regimens using Monte Carlo simulations. The The PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the CLSI (0.5 mg/ L). From our simulations, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg.
Identifiants
pubmed: 37954237
doi: 10.3389/fmicb.2023.1282949
pmc: PMC10634207
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1282949Informations de copyright
Copyright © 2023 Lallemand, Bousquet-Mélou, Chapuis, Davis, Ferran, Kukanich, Kuroda, Lacroix, Minamijima, Olsén, Pelligand, Portugal, Roques, Santschi, Wilson and Toutain.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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