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 (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.
Highlights
IntroductionPiscirickettsia salmonis is a gram-negative bacterium, facultative intracellular, aerobic, pleomorphic, not encapsulated and is the etiological agent of piscirickettsiosis or Salmonid Rickettsial Septicemia (SRS) [2, 3]
Resistance to antimicrobials is a common problem in human and veterinary medicine, the World Organization for Animal Health [1], jointly with FAO/WHO, points out that preventative measures should be carried out under the "One Health" approach; promoting the responsible and prudent use of antimicrobials in the human population as well as in terrestrial and aquatic animals.Piscirickettsia salmonis is a gram-negative bacterium, facultative intracellular, aerobic, pleomorphic, not encapsulated and is the etiological agent of piscirickettsiosis or Salmonid Rickettsial Septicemia (SRS) [2, 3]
In order to assess whether an increase in florfenicol doses is associated with changes in phenotypic susceptibility, this study evaluated the Minimum Inhibitory Concentrations (MICs) of 87 isolates of P. salmonis against florfenicol
Summary
Piscirickettsia salmonis is a gram-negative bacterium, facultative intracellular, aerobic, pleomorphic, not encapsulated and is the etiological agent of piscirickettsiosis or Salmonid Rickettsial Septicemia (SRS) [2, 3] It has affected the Chilean salmon farming industry since 1989 and is characterized by causing high mortality in fish at the fattening stage, the final stage of the productive cycle at sea. This report states that veterinarian-recommended doses of florfenicol for oral therapies range from 20 to 40 mg/kg l.w., even though the Veterinary Medical Registry of Chile recommends a dose of 10 mg/kg l.w. for various salmonid species This is a major concern for both the salmon industry and national authorities, as studies indicating the most appropriate dose of florfenicol in salmonids are lacking
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