Equine veterinarians have been using antimicrobials intra-articularly (IA)—injecting them directly into the joint—for decades, but this route of administration is considered off-label; therefore, there are no established appropriate dosages for practitioners to reference. They most commonly administer antibiotics IA to prevent joint infection, in combination with IA corticosteroids and other medications.

Researchers have shown evidence that some antibiotics are toxic to certain equine joint cells, including cartilage cells (chondrocytes), when used at high doses. Therefore, veterinarians should carefully consider the risks and benefits of any medication being used intra-articularly to reduce damage to joint tissues and minimize antimicrobial resistance.

“The incidence of septic arthritis after a joint injection is low,” said Lynn Pezzanite, DVM, PhD, Dipl. ACVS (Large Animal), assistant professor at Colorado State University’s College of Veterinary and Biomedical Sciences, in Fort Collins, during her presentation at the 2023 Saratoga Vet & Farrier Conference, held Sept. 27-30 in New York. “Even in ambulatory practice it is reported to be less than 0.1%. Further, concurrent antibiotic therapy does not appear to reduce the risk of post-injection infection, except for one study with PSGAG (polysulfated glycosaminoglycan).”

Nonetheless, intra-articular antimicrobial therapy usage appears to be increasing, according to a recent survey described by Pezzanite. “Data consistently show that antimicrobials do not have a significant effect on post-injection infection rates, except when PSGAGs are used.” However, some factors that do contribute to the infection rate include:

• Lack of aseptic technique.
• Using multi­­dose injection vials.
• Experience level of the practitioner.
• Using large-gauge needles.
• Reusing needles (i.e., when the horse moves during an injection and the needle needs to be reinserted).

Based on published studies, Pezzanite said researchers believe there is a lack of rationale for preventative antimicrobial use with IA injections in horses due to the low incidence of infection with joint injections overall.

“Additionally, intra-articular use is off-label and there are no studies supporting the doses currently being used in equine practice,” Pezzanite said. “In fact, intra-articular antimicrobial use has the risk of iatrogenic harm,” or illness related to treatment.

Evidence of Toxicity in Equine Joints

In in vitro (in the laboratory) studies, amikacin, a commonly used antibiotic, was shown to cause cell death within the first two hours of exposure. In explant cultures designed to simulate in vivo (real-life) situations, amikacin significantly decreased the viability of the joint structures.

“Based on these in vitro co-culture studies, amikacin was clearly cytotoxic,” said Pezzanite, or harmful to cells. Therefore, researchers conducted studies in live horses to examine their response to IA amikacin use following joint injections. These researchers found that if veterinarians use IA antibiotics, they should use a very low dose to achieve therapeutic benefits.

In cases of septic arthritis, or active infection of the joint, veterinarians should use alternative antimicrobials that are less toxic than amikacin, such as ampicillin, sulbactam, imipenem, ceftiofur sodium, and amoxicillin, which have all been found to be less cytotoxic to equine joint cells in vitro. Therefore, veterinarians should select the antimicrobial to treat their patient’s infection based on culture and sensitivity findings and use the least toxic option available.

Concurrent Use With PSGAGs, Other Treatments

“The link between PSGAG and sepsis was first recognized decades ago, and 125 mg amikacin administered concurrently did decrease the rate of infection,” said Pezzanite. “However, that study only evaluated a single dose of amikacin, so potentially lower doses could be used to mitigate development of infection, but this has not been studied.”

Antimicrobials are considered contraindicated when injected with cellular products such as mesenchymal stromal cells (MSC) because they might cause MSC death and, therefore, limit the efficacy of the product.

Mitigating Toxic Effects of Amikacin with Other Medications

Although limited, some research shows that the observed toxicity of antimicrobials can be reduced when veterinarians administer them with some other medications.

“In vitro studies show that triamcinolone and hyaluronic acid supported chondrocyte morphology when cultured with amikacin,” said Pezzanite. “These findings suggest that if these drugs are injected at the same time, they may limit the toxicity seen with antimicrobials.”

In another study, researchers found that an oral avocado soybean unsaponifiable (ASU) given in combination with glucosamine and chondroitin, which both play an important role in building and repairing connective tissue, reduced prostaglandin (which acts at the site of tissue damage) production by antibiotic-exposed cartilage cells.

“These findings warrant further investigation in live horses,” said Pezzanite.

Take-Home Message

Depending on the dosage used, antimicrobials are cytotoxic to joint tissues, but more powerful antibiotics such as amikacin are particularly toxic when compared to other antimicrobials. Given the low rate of joint infection following IA injection in horses and lack of evidence supporting the use of antimicrobials to reduce infection, equine practitioners should reconsider preventative antimicrobial use except when injecting PSGAG, said Pezzanite. Veterinarians who inject antimicrobials to treat active infection in horses’ joints can minimize local toxicity by reducing the doses and selecting antimicrobial classes that have lower toxicity.

“Future directions of this work include exploring the long-term effect on athletic performance with intra-articular antimicrobial administration,” said Pezzanite. “In addition, antimicrobial alternates should be considered, and further investigation of other medications that can be co-administered with antimicrobials to decrease toxicity is warranted.”