Diffusion of levofloxacin into bone and synovial tissues.

Abstract

The degree of penetration of an antibiotic into the infected site is an important determinant of therapeutic success. Levofloxacin is widely used in the treatment of serious infections. However, there are only few studies concerning its diffusion into bone tissue and none concerning its diffusion into synovial tissue. Our objective was to quantify levofloxacin bone and synovial tissue penetration and to compare our data with the breakpoint for susceptible organisms. In an open-label study, 12 subjects who were undergoing elective total hip replacement received a single, parenteral, 500 mg dose of levofloxacin. Plasma, cortical and cancellous bone, and synovial tissue samples were collected a mean of 1.2 h later and analysed by a validated HPLC method. The mean +/- S.D. plasma concentration of levofloxacin at the time of bone removal was 7.5 +/- 1.3 mg/L. The levofloxacin concentrations were 7.4 +/- 2.2 mg/kg in cancellous bone tissue and 3.9 +/- 1.2 mg/kg in cortical bone tissue. The levofloxacin concentration was 8.9 +/- 2.1 mg/kg in synovial tissue. The mean +/- S.D. ratios of levofloxacin concentration in bone and plasma (bone/plasma) were 1.0 +/- 0.4 for cancellous bone tissue and 0.5 +/- 0.1 for cortical bone tissue. The ratio of levofloxacin concentration in synovial tissue and plasma (synovial tissue/plasma) was 1.2 +/- 0.4. The concentrations of levofloxacin achieved in cancellous and cortical bone tissue and in synovial tissue are greater than the breakpoint for susceptible organisms, which is < or =2 mg/L.