Effect of lincomycin, an injectable lincosamide antibiotic, against streptococcosis in cultured olive flounder Paralichthys olivaceus and its pharmacokinetic-pharmacodynamic profile

Abstract

Injectable antibiotics have some advantages over oral administration under certain conditions. However, they have not been adopted actively, especially in the aquaculture field. Here, we focused on the effect of intramuscular (i.m.) injection of lincomycin HCl (LH), a lincosamide antibiotic, on a streptococcal infection in olive flounders (Paralichthys olivaceus). In-vitro efficacy tests with 49 Streptococcus parauberis clinical isolates revealed inhibition of 32 isolates (65.3%) by 2 mu g/mL LH, as the 50% minimum inhibitory concentration (MIC50). A single LH i.m. injection (10 mg/kg) in-vivo significantly reduced cumulative mortality rates against S. parauberis infection from 100% to 0-20.0% (P < 0.0001). For pharmacokinetic analysis, LH concentrations in serum and muscle were monitored after single i.m. injection of LH (10 and 20 mg/kg). The peak serum concentration (C-max) was 22.45 mu g/mL (time to peak serum, T-max, 0.25 h) and C-max was 27.40 mu g/mL (T-max, 0.5 h) after a single i.m. dose of 10 and 20 mg/kg, respectively, with the two doses leading to large C-max/MIC50 and T > MIC50 (time period remained above MIC50) values against S. parauberis. After intravenous injection, the volume of distribution (V-z) was high in olive flounder (2.44 L/kg). LH bioavailability was 88.99% following a single i.m. injection of 10 mg/kg. Analyses of muscle residue depletion demonstrated appropriate withdrawal times of 19.95 days (99% statistical tolerance limit) after a single 10 mg/kg i.m. injection. Overall, our results suggest that a single i.m. injection of LH at 10 mg/kg offers acceptable efficacy with reasonable withdrawal periods for streptococcal infection in olive flounder.