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 of Staphylococcus aureus infections. RESULTS: The PK profiles and PK/PD relationship of orbifloxacin against S. aureus were 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 S. aureus. The dose-response analysis indicated that the area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratio over 24 h (AUC24h/MIC) was a strong PK/PD index predictive of antibacterial efficacy (R² >0.98). AUC24h/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-log10, 2-log10, and 3-log10 bacterial reductions, respectively. CONCLUSIONS: The results confirm that AUC24h/MIC is an appropriate PK/PD index for predicting antibacterial efficacy and establish target exposure values required to achieve various levels of bacterial kill.
Read the paper
Related studies
- Structural and topological analysis of thiosemicarbazone-based metal complexes: computational and experimental study of bacterial biofilm inhibition and antioxidant activity
- Toward better cures for Mycobacterium abscessus lung disease
- Challenges for global antibiotic regimen planning and establishing antimicrobial resistance targets: implications for the WHO Essential Medicines List and AWaRe antibiotic book dosing
- Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3‐Triazoles: A Computational Docking Techniques
- Upregulation of pmrA, pmrB, pmrC, phoQ, phoP, and arnT genes contributing to resistance to colistin in superbug Klebsiella pneumoniae isolates from human clinical samples in Tehran, Iran
- Whole-genome sequencing of clinical isolates of Citrobacter Europaeus in China carrying blaOXA−48 and blaNDM−1
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.