Local anesthetics and antibiotics display synergistic and antagonistic drug interactions against pathogens causing septic arthritis in horses.
Abstract: 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. Unassigned: 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. Unassigned: 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. Unassigned: 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. Unassigned: 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.
Publication Date: 2025-02-19 PubMed ID: 39970538DOI: 10.2460/ajvr.24.08.0214Google Scholar: Lookup
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Summary
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This research investigates the effect of combining local anaesthetics with antibiotics to treat septic arthritis in horses, finding that in some cases the combination enhances antibiotic action, while in others it diminishes it.
Research Methodology
- The study explored the impact local anesthetics (LAs) such as bupivacaine hydrochloride, lidocaine hydrochloride, and mepivacaine hydrochloride, when paired with certain antibiotics namely amikacin, ceftiofur, and gentamicin.
- The antibiotic-LA pairs were often used for intrarticular (IA) injections and regional limb perfusion (RLP) in veterinary equine medicine. The researchers aimed to understand what effect these LAs have on antibiotic efficiency.
- To do this, 17 clinical isolates from equine patients were subjected to the checkerboard method, a standard tool used to assess the minimum inhibitory concentration (MIC) needed to inhibit bacterial growth of various antibiotic-LA combinations. This study was conducted between August 2020 and December 2023.
Significant Findings
- The study found that for most combinations, the effectiveness of the antibiotic was not impacted by the addition of the LA.
- However, they found a number of combinations (n = 70) where the LA had either a positive (synergistic; n = 14) or negative (antagonistic; n = 56) effect on the antibiotic’s efficacy.
- In the case of antagonism, increased MICs were seen, but these usually remained within the clinically relevant range, meaning they likely won’t have a significant impact on treatment outcomes.
- One exception was with aminoglycoside-LA combinations, where antagonism resulted in MICs higher than those achievable by RLP, suggesting potential negative impacts on treatment outcomes.
- In synergistic combinations, the MIC often reduced, sometimes from levels way above the clinically relevant range to within or below that range, marking an increased efficacy of the antibiotic due to the LA presence.
Conclusion and Recommendations
- The study concluded that adding LAs to antibiotic solutions for IA injections does not usually compromise antibiotic effectiveness in the treatment of common equine bacterial infections.
- On the contrary, for RLP, adding LAs may decrease antibiotic efficacy at clinically relevant concentrations.
- The researchers therefore caution against carelessly combining LAs with certain aminoglycosides (amikacin and gentamicin) in RLP without considering the specific antimicrobial susceptibility as tested via MICs.
Cite This Article
APA
Adler DMT, Nielsen AT, Olsen C, Verwilghen D, Damborg P, Olsen RH.
(2025).
Local anesthetics and antibiotics display synergistic and antagonistic drug interactions against pathogens causing septic arthritis in horses.
Am J Vet Res, 1-8.
https://doi.org/10.2460/ajvr.24.08.0214 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Goulburn Valley Equine Hospital, Congupna, VIC, Australia.
- Department of Clinical Sciences, School of Veterinary Medicine, University of Melbourne, Melbourne, VIC, Australia.
- Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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