Local anesthetics and antibiotics display synergistic and antagonistic drug interactions against pathogens causing septic arthritis in horses

OBJECTIVE: To investigate the in vitro efficacy of antibiotics (amikacin, ceftiofur, and gentamicin) in combination with local anesthetics (LAs; bupivacaine hydrochloride, lidocaine hydrochloride, and mepivacaine hydrochloride), a combination commonly performed for IA injectate and regional limb perfusion (RLP) in horses.

METHODS: 17 equine clinical isolates were tested by the checkerboard method for their minimum inhibitory concentration (MIC) against a combination of concentrations of LAs and antibiotics from August 2020 through December 2023.

RESULTS: For the majority of combinations, the antibiotic efficacy was not affected. However, in a subset of combinations (n = 70), the addition of LA to the antibiotic solution displayed a synergistic (n = 14) or antagonistic (n = 56) effect, indicating that LA increased or decreased antibiotic activity, respectively. Increased MICs seen in most antagonistic combinations appeared to be without clinical relevance as MICs remained below or above clinically achievable concentrations. In contrast, antagonism observed for aminoglycoside-LA combinations resulted in MICs higher than the concentration achievable by RLP. In some synergistic combinations, MICs decreased from markedly above to below or near clinically achievable concentrations against a specific antibiotic.

CONCLUSIONS: The addition of LAs to antibiotic solutions for IA injections does not compromise the in vitro antibiotic effect. Conversely, the addition for RLPs compromises the in vitro antibiotic effect at clinical concentrations.

CLINICAL RELEVANCE: This in vitro study suggests that LAs can be added to IA antibiotic solutions without compromising antibiotic effects against common equine pathogens. For RLP, the combination of tested aminoglycosides (amikacin and gentamicin) and LAs is discouraged without taking into account MICs of antimicrobial susceptibility testing.