{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T14:53:28Z","timestamp":1775832808551,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Potentiated sulfonamides are widely used in the treatment of porcine respiratory disease complex, but their synergistic activity depends on pathogen-related and pharmacodynamic factors, including the trimethoprim-to-sulfonamide ratio. This study aimed to systematically evaluate the effect of different ratios on in vitro antibacterial interactions against major porcine respiratory pathogens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Trimethoprim was combined with sulfamethoxazole, sulfachloropyridazine, or sulfadiazine at four mass ratios (1:5, 1:10, 1:19, 1:40). Minimum inhibitory concentrations were determined using broth microdilution according to CLSI guidelines. Drug interactions were quantified using the fractional inhibitory concentration index, and a linear mixed-effects model was applied to assess the effects of bacterial species, compound combination, and ratio.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The strongest and most consistent synergistic activity was observed at the 1:5 ratio across most pathogen\u2013drug combinations. Increasing the proportion of the sulfonamide generally reduced synergism and occasionally resulted in antagonistic interactions, particularly in Glaesserella parasuis. Differences between sulfonamides were limited, although sulfachloropyridazine showed higher intrinsic activity against Actinobacillus pleuropneumoniae and G. parasuis, and greater efficacy in combination with trimethoprim against Pasteurella multocida. Statistical analysis confirmed significant effects of both drug ratio and combination on interaction outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that synergism between trimethoprim and sulfonamides is strongly ratio-dependent and cannot be reliably characterized using a single fixed ratio. Ratio-specific evaluation may therefore support more rational antimicrobial use in veterinary medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1805735","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T14:03:22Z","timestamp":1775829802000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative evaluation of trimethoprim-sulfonamide ratios and synergistic interactions against porcine respiratory pathogens"],"prefix":"10.3389","volume":"13","author":[{"given":"Patrik","family":"Mag","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health, and Food Chain Safety, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Klein","sequence":"additional","affiliation":[{"name":"Huvepharma NV","place":["Antwerp, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wouter","family":"Depondt","sequence":"additional","affiliation":[{"name":"Huvepharma NV","place":["Antwerp, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imre S\u00e1ndor","family":"Piross","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]},{"name":"Lend\u00fclet Ecosystem Services Research Group, Institute of Ecology and Botany, HUN-REN Centre for Ecological Research","place":["V\u00e1cr\u00e1t\u00f3t, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9ka","family":"T\u00f3th","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Diseases, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zolt\u00e1n","family":"Somogyi","sequence":"additional","affiliation":[{"name":"Pig-Care Ltd.","place":["Bodajk, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00f3ra","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health, and Food Chain Safety, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1d\u00e1m","family":"Kerek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health, and Food Chain Safety, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1kos","family":"Jerzsele","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]},{"name":"National Laboratory of Infectious Animal Diseases, Antimicrobial Resistance, Veterinary Public Health, and Food Chain Safety, University of Veterinary Medicine Budapest","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s40813-023-00342-w","article-title":"The economic impact of endemic respiratory disease in pigs and related interventions - 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