{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T07:48:43Z","timestamp":1762674523695},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mortality of livestock caused by pathogenic<jats:italic>Escherichia coli<\/jats:italic>(<jats:italic>E<\/jats:italic>.<jats:italic>coli<\/jats:italic>) still accounts for a large proportion of deaths in large\u2010scale production and reproduction, which causes devastating economic losses to the pig breeding industry. The aims of this study were to investigate the antibacterial activity of combined aditoprim (ADP) and sulfamethoxazole (SMZ) against clinical isolates of<jats:italic>E<\/jats:italic>.\u00a0<jats:italic>coli<\/jats:italic>from pigs and to develop a pharmacokinetic\u2013pharmacodynamic (PK\u2010PD) model to formulate the optimal dose of ADP\/SMZ for the treatment of pig colibacillosis. Blood and ileum fluid samples were collected at different times after single intramuscular injection of ADP\/SMZ (5\/25\u00a0mg\/kg b.w.) to healthy pigs and<jats:italic>E.\u00a0coli<\/jats:italic>\u2010infected pigs. Concentrations of ADP and SMZ in plasma and ileum fluid were analyzed by HPLC. The peak concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) and the area under the concentration\u2013time curve (AUC<jats:sub>0\u201024h<\/jats:sub>) in ileum fluid of healthy pigs were 1.76\u00a0\u00b1\u00a00.27\u00a0\u00b5g\/ml and 18.92\u00a0\u00b1\u00a02.87\u00a0\u00b5g\u00b7h\/ml for ADP and 19.15\u00a0\u00b1\u00a02.63\u00a0\u00b5g\/ml and 125.70\u00a0\u00b1\u00a011.86\u00a0\u00b5g\u00b7h\/ml for SMZ, respectively.<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>and AUC<jats:sub>0\u201024h<\/jats:sub>in ileum fluid of infected pigs were 1.88\u00a0\u00b1\u00a00.13\u00a0\u00b5g\/ml and 15.12\u00a0\u00b1\u00a00.75\u00a0\u00b5g\u00b7h\/ml for ADP and 19.71\u00a0\u00b1\u00a03.68\u00a0\u00b5g\/ml and 133.92\u00a0\u00b1\u00a017.14\u00a0\u00b5g\u00b7h\/ml for SMZ, respectively. The minimum inhibitory concentrations (MICs) of combined ADP and SMZ (ADP\/SMZ) against 185 strains of<jats:italic>E<\/jats:italic>.\u00a0<jats:italic>coli<\/jats:italic>from pigs were determined. The MIC<jats:sub>50<\/jats:sub>and MIC<jats:sub>90<\/jats:sub>of ADP\/SMZ were 0.5\/2.5 and 4\/20\u00a0\u00b5g\/ml, respectively. The MIC of the selected pathogenic<jats:italic>E<\/jats:italic>.\u00a0<jats:italic>coli<\/jats:italic>SHC28 was 0.5\/2.5\u00a0\u00b5g\/ml in Mueller\u2010Hinton broth and 0.25\/1.25\u00a0\u00b5g\/ml in ileum fluid, respectively. In vitro, the mutant prevention concentration, the post\u2010antibiotic effect, growth, and time\u2010killing curves in vitro and ex vivo of ADP\/SMZ against the isolate SHC28 were assayed for PD studies. The results showed that ADP\/SMZ exhibited strong concentration\u2010dependent antimicrobial activity against<jats:italic>E<\/jats:italic>.\u00a0<jats:italic>coli<\/jats:italic>. After integrating the in vivo pharmacokinetic parameters of infected pigs and ex vivo PD data using the sigmoid<jats:italic>E<\/jats:italic><jats:sub>max<\/jats:sub>(Hill) equation, the AUC<jats:sub>24h<\/jats:sub>\/MIC values in ileum fluid for bacteriostatic, bactericidal, and bacterial eradication were 18.84, 65.39, and 110.68\u00a0h, respectively. In conclusion, a dosage of 3.45\/17.25\u00a0mg\/kg ADP\/SMZ by intramuscular injection daily for 3 consecutive days may be sufficient to treat swine colibacillosis due to<jats:italic>E<\/jats:italic>.\u00a0<jats:italic>coli<\/jats:italic>with a MIC of 0.5\/2.5\u00a0\u00b5g\/ml.<\/jats:p>","DOI":"10.1111\/jvp.13006","type":"journal-article","created":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T10:45:37Z","timestamp":1629974737000},"page":"133-145","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antibacterial activity of combined aditoprim and sulfamethoxazole against<i>Escherichia coli<\/i>from swine and a dose regimen based on pharmacokinetic\u2013pharmacodynamic modeling"],"prefix":"10.1111","volume":"45","author":[{"given":"Fang","family":"Wang","sequence":"first","affiliation":[{"name":"National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for Detection of Veterinary 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