Tissue pharmacokinetics of levofloxacin in human soft tissue infections

Aims The present study addressed the ability of levofloxacin to penetrate into subcutaneous adipose tissues in patients with soft tissue infection. Methods Tissue concentrations of levofloxacin in inflamed and healthy subcutaneous adipose tissue were measured in six patients by microdialysis after administration of a single intravenous dose of 500 mg. Levofloxacin was assayed by high-performance liquid chromatography. Results The mean concentration vs time profile of free levofloxacin in plasma was identical to that in inflamed and healthy tissues. The ratios of the mean area under the free levofloxacin concentration vs time curve from 0 to 10 h (AUC(0,10 h)) in tissue to that in plasma were 1.2 +/- 1.0 for inflamed and 1.1 +/- 0.6 for healthy subcutaneous adipose tissue (mean +/- SD). The mean difference in the ratio of the AUC(tissue) : AUC(plasma) for inflamed and healthy tissue was 0.09 (95% confidence interval -0.58, 0.759, P > 0.05). Interindividual variability in tissue penetration was high, as indicated by a coefficient of variation of approximately 82% for AUC(tissue) : AUC(plasma) ratios. Conclusions The penetration of levofloxacin into tissue appears to be unaffected by local inflammation. Our plasma and tissue data suggest that an intravenous dose of 500 mg levofloxacin provides effective antibacterial concentrations at the target site. However, in treatment resistant patients, tissue concentrations may be sub-therapeutic.