Optimization of florfenicol dose against Piscirickettsia salmonis in Salmo salar through PK/PD studies
Author
dc.contributor.author
San Martín Núñez, Betty
Author
dc.contributor.author
Fresno, Marcela
Author
dc.contributor.author
Cornejo, Javiera
Author
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Godoy, Marcos
Author
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Ibarra, Rolando
Author
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Vidal, Roberto
Author
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Araneda, Marcelo
Author
dc.contributor.author
Anadón, Arturo
Author
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Lapierre Acevedo, Lisette
Admission date
dc.date.accessioned
2019-10-30T15:40:09Z
Available date
dc.date.available
2019-10-30T15:40:09Z
Publication date
dc.date.issued
2019
Cita de ítem
dc.identifier.citation
PLoS ONE, Volumen 14, Issue 5, 2019,
Identifier
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19326203
Identifier
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10.1371/journal.pone.0215174
Identifier
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https://repositorio.uchile.cl/handle/2250/172544
Abstract
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Salmonid Rickettsial Septicemia (SRS) is the disease of greatest economic importance in the Chilean salmon farming industry, causing high mortality in fish during the final stage of their productive cycle at sea. Since current, commercially available vaccines have not demonstrated the expected efficacy levels, antimicrobials, most commonly florfenicol, are still the main resource for the treatment and control of this pathogen. The aim of this study was to determine the most appropriate single dose of florfenicol, administered through medicated feed, for the treatment of Piscirickettsia salmonis (P. salmonis), using pharmacokinetic/pharmacodynamic (PK/PD) models. Previously, Minimum Inhibitory Concentrations (MICs) of florfenicol were determined for 87 P. salmonis isolates in order to define the epidemiological cut-off point (COWT). The most commonly observed MIC was 0.125 μg mL-1 (83.7%). The COWT value was 0.25 μg mL-1 with a standard deviation of 0.47 log2 μg mL-1 and 0.36 log2 μg mL-1, for Normalized resistance interpretation (NRI) method and ECOFFinder method, respectively. A MIC of 1 μg mL-1 was considered the pharmacodynamic value (PD) to define PK/PD indices. Three doses of florfenicol were evaluated in fish farmed under controlled conditions. For each dose, 150 fish were used and blood plasma samples were collected at different time points (0–48 hours). PK parameters were obtained from curves representing plasma concentrations as a function of time. The results of Monte Carlo simulation indicate that at a dose of 20 mg/Kg l.w. of florfenicol, administered orally as medicated feed, there is 100% probability (PTA) of achieving the desired efficacy (AUC0-24h/MIC>125). According to these results, we suggest that at the indicated dose, the PK/PD cut-off point for florfenicol versus P. salmonis could be 2 μg mL-1 (PTA = 99%). In order to assess the indicated dose in Atlantic salmon, fish were inoculated with P. salmonis LF-89 strain and then treated with the optimized dose of florfenicol, 20 mg/Kg bw for 15 days.