Reconsider Amikacin at Reduced Doses for Joint Injections
Performing joint injections, albeit routine in many sectors of the equine industry, is not without risk. Joint flares or infections can develop that, if not diagnosed and treated promptly, can result in loss of use or life.

To help minimize the development of post-injection infections, almost 50% of equine veterinarians report combining an antimicrobial agent such as amikacin with any medication injected into a joint. Such intra-articular products include polysulfated glycosaminoglycans (PSGAGs), hyaluronic acid, and even corticosteroids.

“Despite being popular, the inclusion of antibiotics in joint injections has not been shown to reduce the risk of infection following injection,” said PhD student Lynn Pezzanite, DVM, MS, Dipl. ACVS (Large Animal), of Colorado State University. “Amikacin is known to be toxic to several mammalian cell types, and the effect of this antibiotic on cells within the joint has not specifically been examined.”

Further, using antibiotics in joints is “off-label” according to drug guidelines, and no data  currently support the doses of antibiotics equine veterinarians use in joints.

During her presentation at the 2019 Annual Convention of the American Association of Equine Practitioners, held Dec. 7-11 in Denver, Colorado, Pezzanite described the steps she and her colleagues took to evaluate the cytotoxicity of amikacin (as well as 14 other antibiotics) to chondrocytes, synoviocytes, as well as stem cells frequently injected into equine joints.

The team took cultures of each cell type and incubated them with various concentrations of amikacin for different times, variable pHs, and with or without synovial fluid. They then analyzed the mechanism of cell death (apoptosis versus necrosis, the latter of which is much more inflammatory).

“We found that amikacin is indeed toxic to cartilage and synovial cells in addition to both bone marrow- and adipose-derived stem cells,” Pezzanite said. “This toxicity occurred in a dose- and pH-independent manner, and the presence of synovial fluid did not mitigate the toxic effects of amikacin. Of the 15 antibiotics evaluated, amikacin was the most toxic to equine chondrocytes.”

The researchers then investigated amikacin in live horses to evaluate:

  1. How long amikacin would remain at therapeutic doses following injection with different doses, and
  2. How amikacin affected the cartilage and inflammatory environment within the joint.

They injected three different doses of amikacin into equine joints and obtained and analyzed joint fluid samples.

“This study in live horses demonstrated that even at the lowest dose of amikacin injected, amikacin concentrations remained at concentrations necessary to kill most common equine pathogens for at least 24 hours,” said Pezzanite. “Furthermore, the higher doses of amikacin investigated caused increased levels of inflammation and biomarkers indicating cartilage damage. These results indicate that doses of amikacin frequently injected by equine veterinarians may be significantly reduced and still be effective to minimize damage to the joint.”

This data set suggests that when used prophylactically (preventively), lower doses of amikacin are likely warranted. Instituting such a dose change might pose clinically challenging, Pezzantie said, considering how ingrained the process of adding amikacin to routine joint injections has become for many equine practitioners.