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.