{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:15:37Z","timestamp":1788966937744,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100013281","name":"Joint Programming Initiative on Antimicrobial Resistance","doi-asserted-by":"publisher","award":["JPIAMR2022\u2010007"],"award-info":[{"award-number":["JPIAMR2022\u2010007"]}],"id":[{"id":"10.13039\/100013281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X03173X\/1"],"award-info":[{"award-number":["MR\/X03173X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm & Therapeutics"],"abstract":"ABSTRACT<\/jats:title>\n \n Trimethoprim (TMP)\u2010sulfonamide combinations are widely used in veterinary medicine, yet the quantitative nature of their pharmacodynamic interaction remains incompletely characterised. This study investigated the interaction between TMP and sulfamethoxazole (SMX), sulfadiazine (SDZ) and sulfadimethoxine (SDMX) against two\n \n Staphylococcus pseudintermedius<\/jats:italic>\n <\/jats:styled-content>\n isolates using minimum inhibitory concentration (MIC) testing, time\u2010kill curve (TKC) experiments and semi\u2010mechanistic pharmacodynamic modelling incorporating a General Pharmacodynamic Interaction (GPDI) framework. TKC assays demonstrated enhanced antibacterial activity for TMP\u2010sulfonamide combinations compared with monotherapy, with the greatest bacterial killing observed at TMP:sulfonamide ratios of 1:4 and 1:19. The final GPDI model identified a predominantly unidirectional interaction in which sulfonamides increased TMP potency through concentration\u2010dependent reductions in TMP EC\n 50<\/jats:sub>\n of 86%\u201396% at saturating sulfonamide concentrations, corresponding to approximately 7\u2010 to 26\u2010fold maximal possible increases in TMP potency. Maximal synergy differed between sulfonamides, occurring at approximately 1:20 for TMP\/SMX (~75% increase in killing), 1:40 for TMP\/SDZ (~181%) and 1:5 for TMP\/SDMX (~80%). Pharmacokinetic\u2010pharmacodynamic simulations of clinically relevant canine dosing regimens predicted transient bacterial suppression but not bacterial eradication. These findings demonstrate that TMP\u2010sulfonamide synergy is dynamic, concentration\u2010dependent and bacterial species\u2010specific, highlighting the importance of PK\/PD\u2010informed optimisation of potentiated sulfonamide therapy in veterinary medicine.\n <\/jats:p>","DOI":"10.1111\/jvp.70107","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:26:51Z","timestamp":1788964011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative Pharmacodynamic Analysis of Trimethoprim\u2010Sulfonamide Combination Activity Against\u00a0\n Staphylococcus pseudintermedius<\/i>"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3550-3030","authenticated-orcid":false,"given":"Andrew","family":"Mead","sequence":"first","affiliation":[{"name":"Pathobiology and Population Sciences (PPS), APPRAISE Laboratory The Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6930-9327","authenticated-orcid":false,"given":"Alexis","family":"Viel","sequence":"additional","affiliation":[{"name":"CiMMEx Unit, Foug\u00e8res Laboratory ANSES Foug\u00e8res France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Boulanger","sequence":"additional","affiliation":[{"name":"CiMMEx Unit, Foug\u00e8res Laboratory ANSES Foug\u00e8res France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5495-1640","authenticated-orcid":false,"given":"Gudrun","family":"Overesch","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Bacteriology, Vetsuisse Faculty University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7480-9935","authenticated-orcid":false,"given":"Carl","family":"Ekstrand","sequence":"additional","affiliation":[{"name":"Department of Animal Biosciences Swedish University of Agricultural Sciences Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Louis","family":"Toutain","sequence":"additional","affiliation":[{"name":"ENVT, INTHERES Universit\u00e9 de Toulouse Toulouse France"},{"name":"Comparative Biomedical Sciences, APPRAISE The Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6629-1088","authenticated-orcid":false,"given":"Aude A.","family":"Ferran","sequence":"additional","affiliation":[{"name":"ENVT, INTHERES Universit\u00e9 de Toulouse Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6005-1975","authenticated-orcid":false,"given":"Ludovic","family":"Pelligand","sequence":"additional","affiliation":[{"name":"Comparative Biomedical Sciences, APPRAISE The Royal Veterinary College London UK"},{"name":"Clinical Services and Sciences The Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"issue":"4","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1046\/j.1365-2885.2001.00337.x","article-title":"Pharmacokinetics and Bioavailability of Sulfadiazine and Trimethoprim (Trimazin 30%) After Oral Administration in Non\u2010Fasted Young Pigs","volume":"24","author":"Baert K.","year":"2001","journal-title":"Journal of Veterinary Pharmacology and Therapeutics"},{"issue":"5","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1023\/A:1012299115260","article-title":"Ways to Fit a PK Model With Some Data Below the Quantification Limit","volume":"28","author":"Beal S. 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