Three fluoroquinolones with different epithelial lining fluid penetration in a murine lung infection model: an experimental site-specific PK/PD study
Abstract
ABSTRACT Antimicrobial efficacy in pneumonia is strongly influenced by site-specific drug exposure; however, pharmacokinetic/pharmacodynamic (PK/PD) indices based on plasma concentrations may not adequately reflect drug exposure at the pulmonary infection site. This study evaluated how differences in pulmonary distribution influence the magnitude and interpretation of PK/PD targets by comparing three fluoroquinolones with distinct epithelial lining fluid (ELF) penetration profiles. Using a murine Streptococcus pneumoniae lung infection model, levofloxacin (LVFX), garenoxacin (GRNX), and lascufloxacin (LSFX) were evaluated under identical experimental conditions. Minimum-inhibitory concentrations (MICs) were determined by broth microdilution. Pharmacokinetics were assessed in plasma and ELF, and pharmacodynamics were quantified as changes in pulmonary bacterial burden. PK/PD relationships and exposure targets were estimated based on plasma- and ELF-derived indices. The MICs of LVFX, GRNX, and LSFX were 0.512, 0.032, and 0.032 mg/L, respectively. In plasma-based PK/PD analyses, GRNX and LSFX exhibited bactericidal effects at lower f AUC/MIC values than LVFX. In contrast, ELF-based analyses revealed greater interdrug differences in PK/PD targets attributable to differences in ELF penetration. Notably, LSFX showed substantial divergence between plasma- and ELF-based PK/PD targets, indicating a strong influence of site-specific exposure on antibacterial efficacy. When ELF-based…
Read the paper
Related studies
- Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
- Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors
- Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy
- Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)
- GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
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.