{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T01:51:40Z","timestamp":1764813100954,"version":"3.40.4"},"reference-count":27,"publisher":"American Veterinary Medical Association (AVMA)","issue":"5","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>Objective<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>Methods<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>Results<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>Clinical Relevance<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.24.08.0214","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T15:48:39Z","timestamp":1739980119000},"source":"Crossref","is-referenced-by-count":1,"title":["Local anesthetics and antibiotics display synergistic and antagonistic drug interactions against pathogens causing septic arthritis in horses"],"prefix":"10.2460","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-0810","authenticated-orcid":true,"given":"Ditte M. T.","family":"Adler","sequence":"first","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ane T.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Verwilghen","sequence":"additional","affiliation":[{"name":"Goulburn Valley Equine Hospital, Congupna, VIC, Australia"},{"name":"Department of Clinical Sciences, School of Veterinary Medicine, University of Melbourne, Melbourne, VIC, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Damborg","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rikke H.","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"issue":"6","key":"B1","series-title":"Vet Surg","first-page":"610","article-title":"Synovial fluid and plasma concentrations of ceftiofur after regional intravenous perfusion in the horse","volume":"34","author":"Pille F","year":"2005","unstructured":"Pille F, De Baere S, Ceelen L, et al. Synovial fluid and plasma concentrations of ceftiofur after regional intravenous perfusion in the horse. Vet Surg. 2005;34(6):610\u2013617. doi:10.1111\/j.1532-950X.2005.00095.x"},{"issue":"8","key":"B2","series-title":"Vet Surg","first-page":"1071","article-title":"Methods and variables associated with the risk of septic arthritis following intra-articular injections in horses: a survey of veterinarians","volume":"45","author":"Gillespie CC","year":"2016","unstructured":"Gillespie CC, Adams SB, Moore GE. Methods and variables associated with the risk of septic arthritis following intra-articular injections in horses: a survey of veterinarians. 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Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses. Am J Vet Res. 1990;51(9):1363\u20131369. doi:10.2460\/ajvr.1990.51.09.1363"},{"issue":"5","key":"B5","series-title":"Vet Surg","first-page":"398","article-title":"Determination of synovial fluid and serum concentrations, and morphologic effects of intraarticular ceftiofur sodium in horses","volume":"29","author":"Mills ML","year":"2000","unstructured":"Mills ML, Rush BR, Jean GS, et al. Determination of synovial fluid and serum concentrations, and morphologic effects of intraarticular ceftiofur sodium in horses. 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Systemic and local effects of lidocaine or mepivacaine when used for intravenous regional anaesthesia of the distal limb in standing sedated horses. Equine Vet J. 2020;52(5):743\u2013751. doi:10.1111\/evj.13236"},{"key":"B12","series-title":"Diagnosis and Management of Lameness in the Horse","first-page":"100","article-title":"Diagnostic analgesia","author":"Bassage L","year":"2010","unstructured":"Bassage L, Ross M. Diagnostic analgesia. In: Ross M, Dyson S, eds. Diagnosis and Management of Lameness in the Horse. 2nd ed. Elsevier; 2010:100\u2013135."},{"key":"B13","series-title":"Vet J","first-page":"27","article-title":"The antimicrobial activity of bupivacaine, lidocaine and mepivacaine against equine pathogens: an investigation of 40 bacterial isolates","volume":"223","author":"Adler DMT","year":"2017","unstructured":"Adler DMT, Damborg P, Verwilghen DR. 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