Abstract

Previous research has demonstrated the feasibility of the giant danio (Devario aequinpinnatus) as a model animal for pharmacokinetic research, however, up to this point only oxytetracycline has been tested in this species.^1,2 In this study we tested two further antibiotics commonly used in veterinary care of laboratory and pet teleost fish: florfenicol and enrofloxacin. Florfenicol was administered orally via gavage feeding. Enrofloxacin was administered orally via gavage feeding and as a 6-hour immersion bath. Following administration of antibiotics, animals were euthanized to allow for blood and muscle sample collection up to 48 hours after antibiotic therapy, and Monte Carlo simulations were created to model pharmacokinetics and pharmacodynamics.

Oral gavage administration of florfenicol at 60 mg/kg was sufficient to exceed minimum inhibitory concentrations (MIC) of 4 mg/L (fAUC_0-24/MIC targets of 24–60 were used for modelling), which is sufficient to treat susceptible bacteria.³ Oral gavage administration of enrofloxacin at 8 mg/kg was sufficient to exceed MICs of 0.125 mg/L to 0.25 mg/L (fAUC_0-24/MIC targets of 30 and 70 were used), while bath concentrations of 10 mg/L were only able to exceed MICs of 0.0313 mg/L to 0.0625 mg/L (fAUC_0-24/MIC targets of 30 and 70 were used). At the doses in this study, oral enrofloxacin administered once per day would be expected to treat susceptible bacteria successfully, but bath administration once per day may be insufficient for treatment and may instead produce antibiotic resistance.⁴ A potential source for the lack of success of the bath administration of enrofloxacin is the known interaction of the antibiotic with calcium and magnesium in the water, potentially lowering bioavailability.⁵

Acknowledgements

The authors thank the USDA NIFA Southern Regional Aquaculture Center for funding, the University of Florida for providing the facilities and additional support, and 5D Tropical Inc. for supplying fish.

*Presenting author

Literature Cited

1.  Vorbach BS, Chandasana H, Derendorf H, Yanong RPE (2019). Pharmacokinetics of oxytetracycline in the giant danio (Devario aequipinnatus) following bath immersion. Aquaculture 498:12–16.

2.  Vorbach BS, Chandasana H, Derendorf H, Yanong RPE (2018). Pharmacokinetics of oxytetracycline in the giant danio (Devario aequipinnatus) after bath immersion: effect of calcium and recommendations for bath therapy. 49th International Association for Aquatic Animal Medicine Conference, Long Beach, CA.

3.  Dung TT, Haesebrouck F, Tuan NA, Sorgeloos P, Baele M, Decostere A. 2008. Antimicrobial susceptibility pattern of Edwardsiella ictaluri isolates from natural outbreaks of bacillary necrosis of Pangasianodon hypophthalmus in Vietnam. Microb Drug Resist 14(4):311–316.

4.  Griffin MJ, Reichley SR, Greenway TE, Quiniou SM, Ware C, Gao DX, Gaunt PS, Yanong RPE, Pouder DB, Hawke JP, Soto E. 2016. Comparison of Edwardsiella ictaluri isolates from different hosts and geographic origins. J Fish Dis 39:947–969.

5.  Plumb DC. 2015. Plumb’s Veterinary Drug Handbook 9th Ed. Wiley-Blackwell, Ames, Iowa.