Optimizing tylosin dosage for co-infection of Actinobacillus pleuropneumoniae and Pasteurella multocida in pigs using pharmacokinetic/pharmacodynamic modeling

Formulating a therapeutic strategy that can effectively combat concurrent infections of Actinobacillus pleuropneumoniae ( A. ) and Pasteurella multocida P. be challenging. This study aimed to 1) establish minimum inhibitory concentration (MIC), bactericidal (MBC), time kill curve, post-antibiotic effect (PAE) tylosin against pig isolates employ the MIC data for development epidemiological cutoff (ECOFF) values; 2) estimate pharmacokinetics (PKs) following its intramuscular (IM) administration (20 mg/kg) in healthy infected pigs; 3) PK–pharmacodynamic (PD) integrated model predict optimal dosing regimens PK/PD values pigs. The both 89 363 strains spread widely, ranging from 1 256 μg/mL 0.5 128 μg/mL, respectively. According European Committee on Antimicrobial Susceptibility Testing (EUCAST) ECOFFinder analysis ECOFF value (≤64 µg/mL), 97.75% (87 strains) pleuropnumoniae were wild-type, whereas with same 99.72% (363 multicoda considered wild-type tylosin. Area under curve (AUC), T 1/2 , C max significantly greater pigs than those (13.33 h × 1.99 h, 5.79 vs. 10.46 1.83 3.59 respectively) p < 0.05). In pigs, AUC 24 /MIC bacteriostatic activity 0.98 1.10 h; activity, 1.97 1.03 1.12 2.54 2.36 Monte Carlo simulation lead 2 calculated cutoff. Managing co-infections present challenges, as it often demands multiple antibiotics address diverse pathogens. However, using tylosin, which targets may enhance control bacterial burden. By employing an optimized dosage 11.94–15.37 mg/kg 25.17–27.79 result achieving effects 90% co-infected