Investigating antibiotic joint toxicity

Injecting medications such as corticosteroids and polysulphated glycosaminoglycans (PSGAGs)

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directly into a joint is a common procedure in equine practice. Antibiotics are often administered at the same time in the hope of reducing the risk of infection.

However, little is known about damage the antibiotics themselves cause to joint tissues

Lynn Pezzanite, and colleagues at the Translational Medicine Institute, College of Veterinary Medicine and Biomedical Sciences, Colorado State University conducted a laboratory study to investigate the effect of different antibiotics on preparations of chondrocytes (cartilage cells) and synoviocytes.

Their aim was to determine the half maximal inhibitory concentration (IC50 - the concentration of antibiotic at which 50% of the cells are viable) for various antibiotics. They could then use this information to assess which ones were likely to be safest to use for equine joint injection.

They incubated cartilage cells in the laboratory in the presence of different concentrations of various antibiotics. Fifteen antibiotics were assessed, including various aminoglycosides, penicillins, and cephahosporins.

After incubating the cell /antibiotic preparations, the research team used specialised staining techniques to identify dead cells.

They found that antibiotics decreased the viability of equine chondrocytes and synovial cells in a dose-dependent manner, which varied between and within antimicrobial classes.  

Aminoglycosides (eg amikacin) and doxycycline were the most toxic (ie they had the lowest IC50 – the lowest concentration of antibiotic required to kill 50% of the cells).

Having the least detrimental effect were ampicillin sulbactam, imipenem, tobramycin, ceftiofur sodium and amoxicillin, which had IC50 >25mg/ml. (25mg/ml was the highest concentration of antibiotic tested as this was considered to be the concentration likely to be reached with doses currently used for joint medication.)

A full report of the research is published in the Equine Veterinary Journal.

The authors conclude that antibiotics have a dose-dependent toxic effect on equine chondrocytes and synovial cells in vitro, which varied between and within antimicrobial classes.  

They suggest that further work is needed to relate these results to the real-life situation. Equine practitioners may then be able to limit damage to joint tissues when choosing which antibiotic and dose to use for intra-articular medication.

 

For more details, see:

Use of in Vitro Assays to Identify Antibiotics That Are Cytotoxic to Normal Equine Chondrocytes and Synovial Cells

Lynn Pezzanite, Lyndah Chow, Gabriella Piquini, Gregg Griffenhagen, Dominique Ramirez, Steven Dow, Laurie Goodrich

Equine Vet J (2020)

doi: 10.1111/evj.13314