In vivo pharmacokinetic and pharmacodynamic profiles of orbifloxacin against Staphylococcus aureus in a neutropenic murine thigh infection model.

Abstract

BACKGROUND: Orbifloxacin is a broad-spectrum fluoroquinolone antibiotic developed for veterinary use in the treatment of skin and soft tissue infections, as well as respiratory tract infections. This study aimed to define the pharmacokinetic/pharmacodynamic (PK/PD) indices and target exposures associated with antibacterial activity, thereby providing a rational framework for the development and optimization of orbifloxacin dosing regimens in the treatment ofinfections. RESULTS: The PK profiles and PK/PD relationship of orbifloxacin againstwere investigated using a neutropenic murine thigh infection model with multiple dosing regimens. Orbifloxacin exhibited a short-duration post-antibiotic effect (PAE; 0.12–2.45 h) and a longer post-antibiotic sub-MIC effect (PA-SME; 2.13–5.29 h) against. The dose-response analysis indicated that the area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratio over 24 h (AUC/MIC) was a strong PK/PD index predictive of antibacterial efficacy (R² >0.98). AUC/MIC targets of 33.78–37.79 h, 53.30–61.56 h, 88.59–98.35 h, and 179.43–217.47 h were required to achieve bacteriostatic, 1-log, 2-log, and 3-logbacterial reductions, respectively. CONCLUSIONS: The results confirm that AUC/MIC is an appropriate PK/PD index for predicting antibacterial efficacy and establish target exposure values required to achieve various levels of bacterial kill. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-025-04974-8.