Pharmacodynamic Profiling of Amoxicillin: Targeting Multidrug-Resistant Gram-Positive Pathogens Staphylococcus aureus and Staphylococcus pseudintermedius in Canine Clinical Isolates

The rising threat of antimicrobial resistance (AMR) is a global concern in both human and veterinary medicine, with multidrug-resistant (MDR) pathogens such as <i>Staphylococcus aureus</i> and <i>Staphylococcus pseudintermedius</i> presenting significant challenges. <b>Background/Objectives</b>: This study evaluates the effectiveness of amoxicillin against these MDR pathogens in canine isolates using pharmacokinetic and pharmacodynamic parameters. <b>Methods</b>: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and mutation prevention concentration (MPC) were assessed. Additionally, time-kill assays and post-antibiotic effect (PAE) assessments were performed. Epidemiological cutoff (ECOFF) values were established for both species to guide therapy. <b>Results</b>: <i>S. aureus</i> had a higher resistance rate (35.89%) than <i>S. pseudintermedius</i> (15.27%), with MIC50 values of 0.50 μg/mL and 0.25 μg/mL, respectively. The MPC analysis revealed that <i>S. pseudintermedius</i> required higher antibiotic concentrations (16.11 μg/mL) to prevent mutations compared to <i>S. aureus</i> (2.20 μg/mL). Time-kill assays indicated that higher amoxicillin dosages caused faster bacterial reduction. The PAE analysis showed extended post-treatment bacterial suppression at elevated doses, particularly against <i>S. aureus</i>. <b>Conclusions</b>: Species-specific amoxicillin dosing strategies are necessary due to differing resistance and susceptibility profiles between <i>S. aureus</i> and <i>S. pseudintermedius</i>. High-dose amoxicillin therapy is recommended to achieve optimal therapeutic outcomes for resistant SA, while slightly adjusted dosing can manage <i>S. pseudintermedius</i> infections. These findings provide essential insights for veterinary antimicrobial stewardship, underscoring the need for tailored therapeutic approaches to minimize AMR development while ensuring effective infection control.