Diffusion of Cefepime into Cancellous and Cortical Bone Tissue

Abstract

The degree of penetration of an antibiotic into the infection site is an important factor in its therapeutic efficacy, particularly in bone and joint infections. In the present study, we examined the bone tissue penetration of cefepime at a dose of 2 g, and the results were correlated to microbiological data to estimate the clinical efficacy of cefepime in bone infections.In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 2 g dose of cefepime. Plasma samples were collected simultaneously with bone tissue samples 1.5 hours later, on average, and analyzed by a validated high performance liquid chromatography assay.Ten patients (7 women and 3 men; mean age, 78 years; mean body weight, 57 Kg; mean creatinine clearance, 56 mL/min) were enrolled. The mean ± SD plasma concentration of cefepime at the time of bone removal was 72.9 ± 24.4 μg/mL. The mean ± SD cefepime concentrations were 73.5 ± 16.2 μg/mL in cancellous bone tissue and 67.7 ± 17.0 μg/mL in cortical bone tissue. The mean ± SD ratios of cefepime concentration in bone and plasma (bone/plasma) were 1.06 ± 0.23 for cancellous bone tissue and 0.87 ± 0.37 for cortical bone tissue.Cefepime exhibits an excellent diffusion into bone tissue, with concentrations achieved in both cancellous and cortical bone tissue greater than the minimum concentrations required to inhibit the growth of 90% of strains (MIC90) of most of the susceptible pathogens commonly involved in bone infections.