Abstract
Enrofloxacin is a fluoroquinolone widely used in animals including fish. It is effective against important fish pathogens including Aeromonas spp., Pseudomonas spp., and many other gram-negative pathogens. Intramuscular injection of enrofloxacin is a feasible and efficacious option for drug delivery. However, in many species, including horses, cattle, small mammals, birds, and companion exotics, intramuscular injection has been associated with injection site reactions and increases in serum muscle enzymes.1-5 This is thought to be secondary to the 11.5 pH of the 2.27% (22.7 mg/ml) injectable formulation.6 The occurrence of injection site reactions has not been reported in fish. Striped bass (Morone saxatilis) from an aquaculture research facility were used in this study. Each fish was scheduled to be euthanized while under anesthesia following exploratory celiotomy as part of a teaching laboratory at the North Carolina State University College of Veterinary Medicine. All procedures were approved by the university IACUC. Three groups of eight fish were included in the study. All fish were anesthetized with MS-222 and received an intramuscular injection of enrofloxacin 2.27% in the right epaxial musculature, mean 7.69 mg/kg, range 6.14 to 9.69 mg/kg. The groups were injected 24, 48, or 96 hours prior to evaluation. The 24 and 48-hour groups received an injection of equal volume 0.9% saline in the left epaxial musculature. A 5 mm wide cross-section of skin and underlying muscle was collected at each injection site and fixed in 10% neutral buffered formalin for histopathology. A corresponding non-injected tissue sample was collected from the left epaxial musculature from each fish of the 96-hour group. All tissue sections were evaluated under light microscopy and assigned a tissue reaction grade of 1–4. Grades corresponded to normal tissue (1), mild changes including early necrosis and mild hemorrhage limited to the area of needle insertion (2), moderate changes similar to grade 2 but extending throughout the injection site, with more extensive hemorrhage and mild inflammation (3), or severe changes encompassing all features of grade 3 with more severe inflammation and advanced stages of necrosis (4). Externally all control and injection sites appeared visually unremarkable. On dissection, epaxial muscle of the enrofloxacin-injected tissue appeared moderately to severely hemorrhagic compared to saline and non-injected tissue, which was normal or mildly hemorrhagic. Histologically, 8/8 non-injected tissues were grade 1. For saline injected tissues, 14/16 tissues were grade 2 and two samples were grade 3. There was no difference between 24 and 48 hours. For enrofloxacin injected tissues, 8/8 of the 24-hour samples were grade 3 and 16/16 of the 48 and 96-hour samples were grade 4. These data show that intramuscular injection of enrofloxacin 2.27% is associated with severe hemorrhage, necrosis, and inflammation in striped bass within 48 hours after injection. Intramuscular injections may negatively affect animal welfare and have significant adverse effects. Intramuscular enrofloxacin injection is not recommended in striped bass and alternative treatment approaches should be considered in teleost fish.
Acknowledgements
The authors thank Ryan Kelly of the Marine Aquaculture Research Center of North Carolina State University and Heather Broadhurst of the North Carolina Aquariums for their contributions to this project.
* Presenting author, Student presenter
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