Optimization of florfenicol dose against Piscirickettsia salmonis in Salmo salar through PK/PD studies

Abstract

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 (CO WT ). The most commonly observed MIC was 0.125 μg mL -1 (83.7%). The CO WT value was 0.25 μg mL -1 with a standard deviation of 0.47 log 2 μg mL -1 and 0.36 log 2 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 (AUC 0-24h /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.

Florfenicol and oxytetracycline susceptibility patterns in Chilean isolates of Tenacibaculum dicentrarchi: An emerging pathogen for farmed salmonids

“…dicentrarchi could have different strategies for coping with antimicrobials (publication in process). However, the Veterinary Medical Registry of Chile currently recommends a dose of 10 mg/kg for various salmonid species (San Martín et al., 2019), with authorization required for any extra‐label treatment. This regulatory gap might be addressed by the aforementioned empirical research made possible by determinations of MIC values.…”

Horizontal transmission of Piscirickettsia salmonis from the wild sub‐Antarctic notothenioid fish Eleginops maclovinus to rainbow trout (Oncorhynchus mykiss) under experimental conditions

“…The bacterial inoculum applied to shedder fish, its concentration and dose are similar to those used in several studies, including cohabitation challenges (Rozas‐Serri et al., 2017; San Martín et al., 2019; Svenning et al., 2019).…”

Antibacterial treatment of lumpfish (Cyclopterus lumpus) experimentally challenged with Vibrio anguillarum, atypical Aeromonas salmonicida and Pasteurella atlantica

“…anguillarum and atypical A. salmonicida is that the latter induce formation of white nodules in kidney and other organs in lumpfish (this study and Rønneseth, Brudal, et al., 2017). Although FFC is efficient against intracellular microorganisms such as Piscirickettsia salmonis (Henriquez et al., 2016; San Martín et al., 2019), theoretically the nodule structure may reduce access of the antibacterials into the core of the nodule and result in concentrations of antibacterial agents being too low to effectively combat the bacteria. Even a small number of surviving bacteria can be enough to resume the disease.…”