{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T01:28:01Z","timestamp":1789003681249,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"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"}]},{"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Trailing endpoints are a recognised challenge in broth microdilution MIC testing, particularly for bacteriostatic agents such as trimethoprim (TMP) and sulphonamides. In this study, we applied a pharmacodynamically guided refinement to determine the MIC of the combination against\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus pseudintermedius<\/jats:italic>\n                    <\/jats:styled-content>\n                    ; we did not aim at redefining clinical susceptibility, but at refining MIC determination to better guide pharmacodynamic study design. By providing more reliable thresholds for growth suppression, this approach supports optimisation of PD modelling and may ultimately inform translational applications, such as dose prediction and reducing misclassification in PD contexts. Visual MICs were compared to those derived from log\n                    <jats:sub>10<\/jats:sub>\n                    changes in CFU\/mL over 24\u2009h, using pharmacodynamic thresholds of +2.3 log\n                    <jats:sub>10<\/jats:sub>\n                    (growth from standard inoculum of 5\u2009\u00d7\u200910\n                    <jats:sup>5<\/jats:sup>\n                    to ~10\n                    <jats:sup>8<\/jats:sup>\n                    \u2009CFU\/mL, corresponding to visible growth MIC) and 0 log\n                    <jats:sub>10<\/jats:sub>\n                    change (stationary concentration). Across 10 clinical isolates, visual MICs often underestimated the concentration required to suppress growth by 2\u20134 fold (more than one dilution step), particularly for sulphonamides. TMP\u2010sulphonamide combinations at a 1:19 ratio showed reduced trailing and closer agreement between visual and count\u2010based MICs, reflecting enhanced bactericidal activity. Time\u2010kill curve experiments anchored on the log\n                    <jats:sub>10<\/jats:sub>\n                    count\u2010based MIC provided a well\u2010distributed range of PD responses, capturing both suppression and killing more accurately than curves centred on visual MICs. This method supports more rational selection of concentrations for PD studies and may be especially valuable for slow\u2010acting or ratio\u2010sensitive combinations, and has translational value for sulphonamides, such as sulfamethoxazole, used in both human and veterinary medicine.\n                  <\/jats:p>","DOI":"10.1111\/jvp.70033","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:20:29Z","timestamp":1761664829000},"page":"220-227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Time Kill Curve\n                    <scp>PD<\/scp>\n                    Modelling Experiments Are Affected by Trailing\n                    <scp>MIC<\/scp>\n                    Endpoints: Refinement of\n                    <scp>MIC<\/scp>\n                    Determination for\n                    <scp>\n                      <i>S. pseudintermedius<\/i>\n                    <\/scp>"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3550-3030","authenticated-orcid":false,"given":"Andrew","family":"Mead","sequence":"first","affiliation":[{"name":"Comparative Biomedical Sciences The Royal Veterinary College  London UK"}],"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 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":[[2025,10,28]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"51","volume-title":"Antibiotics in Laboratory Medicine","author":"Amsterdam D.","year":"2015"},{"key":"e_1_2_6_3_1","first-page":"M07","volume-title":"Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard","author":"Clinical and Laboratory Standards Institute","year":"2024"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro862"},{"key":"e_1_2_6_5_1","unstructured":"EUCAST.2000.\u201cDetermination of Minimum Inhibitory Concentrations (MICs) of Antibacterial Agents by Agar Dilution.\u201d EUCAST Definitive Document E.Def 3.1 European Committee on Antimicrobial Susceptibility Testing.https:\/\/www.clinicalmicrobiologyandinfection.com\/article\/S1198\u2010743X(14)63158\u2010X\/fulltext."},{"key":"e_1_2_6_6_1","unstructured":"EUCAST.2021.\u201cMIC Distributions and the Setting of Epidemiological Cut\u2010Off Values (ECOFF) Value.\u201d EUCAST SOP 10.2 2021 European Committee on Antimicrobial Susceptibility Testing.http:\/\/www.eucast.org."},{"key":"e_1_2_6_7_1","unstructured":"EUCAST.2024.\u201cReading Guide for Broth Microdilution.\u201d Version 5.0 European Committee on Antimicrobial Susceptibility Testing.http:\/\/www.eucast.org."},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11040427"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2021.125686"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki079"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544020-00005"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.2.369-377.2004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005769"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2023.102427"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2022.102269"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00951-20"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1054\/drup.2000.0146"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00433-18"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12917"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00047-06"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.5812\/jjm.28666"}],"container-title":["Journal of Veterinary Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.70033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvp.70033","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.70033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:33:46Z","timestamp":1773034426000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvp.70033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/jvp.70033"],"URL":"https:\/\/doi.org\/10.1111\/jvp.70033","archive":["Portico"],"relation":{},"ISSN":["0140-7783","1365-2885"],"issn-type":[{"value":"0140-7783","type":"print"},{"value":"1365-2885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]},"assertion":[{"value":"2025-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}