Synergistic effect and resistance prevention activity of antimicrobial peptide MPX with Tulathromycin against

Introduction: The emergence and dissemination of multidrug-resistant Methods: To assess synergism, the minimum inhibitory concentrations (MICs) of MPX and Tul, both individually and in combination, were determined using the micro-broth dilution method and checkerboard assay. Time-kill assays were conducted to analyze antibacterial activity and kill rate by quantifying viable bacterial counts. The post-antibiotic effect (PAE) was calculated following exposure to 1-2 MIC of each drug alone and in combination. For resistance prevention analysis, serial passage experiments were performed over 30 generations under selective pressure at 1/4 MIC for each agent to monitor changes in MIC values. Additionally, the mutant prevention concentration (MPC) was measured to evaluate MPX's capacity to narrow the MSW of Tul against APP. Finally, the antimicrobial activity of MPX and Tul was assessed against resistant APP strains. Results and discussion: The fractional inhibitory concentration index (FICI) indicated an indifferent interaction (1.5) for susceptible strains and an additive effect (0.75) for resistant strains. Time-kill curves demonstrated that MPX significantly enhanced the antibacterial efficacy of Tul against APP. Specifically, the kill rate within 0-1 hour and the PAE at 1-2 MIC of Tul increased from 0.35-2.91 to 1.41-5.03 Log