PK/PD Modeling of a Novel Pleuromutilin Derivative Pleuro2-4 against Mycoplasma gallisepticum in Chicks.

Mycoplasma gallisepticum is a major causative agent of chronic respiratory disease in poultry, and effective antimicrobial therapy remains essential for disease control. In this study, the antimycoplasmal activity, pharmacokinetics, therapeutic efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) model of Pleuro2-4, a novel pleuromutilin candidate, were systematically evaluated against M. gallisepticum. Pleuro2-4 exhibited potent in vitro activity (MIC = 0.0078 μg/mL) and concentration-dependent killing. Following oral administration in chicks, Pleuro2-4 was rapidly converted to its active metabolite and displayed rapid absorption and sustained exposure in lung tissue. In an M. gallisepticum infection model, Pleuro2-4 alleviated respiratory lesions, reduced mycoplasmal loads, and suppressed inflammatory responses. PK/PD integration using an inhibitory sigmoid Emax model identified AUC0-24h/MIC as the PK/PD index for dose optimization. The bactericidal target was 3372.82 h, corresponding to a recommended oral dosage of 44.99 mg/kg once daily for three consecutive days. These findings support Pleuro2-4 as a promising candidate for avian mycoplasmosis treatment.