Diffusion of ertapenem into bone and synovial tissues

Abstract

The degree of penetration of an antibiotic into the infected site is an important criterion for therapeutic success. Ertapenem is a new carbapenem, exhibiting activity against most Gram-positive and Gram-negative aerobic and anaerobic bacteria commonly recovered from community-acquired infections. However, no studies concerning its diffusion into bone and synovial tissue are available. Our objective was to quantify ertapenem bone and synovial tissue penetration and to compare our data with the MIC(90)s for causative pathogens. In an open-label study, 18 patients who were undergoing elective total hip replacement received a single, parenteral, 1 g dose of ertapenem. One serum, one cortical and cancellous bone and one synovial tissue sample was collected per patient a median [interquartile range (IQR)] of 1.6 (1.5-1.7), 12.4 (11.9-13.1) or 23.8 h (22.6-25.2) later and analysed by HPLC. The median (IQR) serum concentrations of ertapenem were 70.1 (56.1-75.9), 10.0 (9.1-11.2) and 2.6 mg/L (2.3-3.0), respectively, at the different time points. The median (IQR) cancellous bone tissue concentrations were 13.2 (10.2-14.8), 1.9 (1.7-2.1) and 0.6 microg/g (0.4-0.6) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.19 (0.18-0.23). The median (IQR) cortical bone tissue concentrations were 8.0 (6.5-9.5), 1.3 (1.2-1.3) and 0.3 microg/g (0.3-0.4) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.13 (0.12-0.14). The median (IQR) synovial tissue concentrations were 26.2 microg/g (22.7-28.4), 4.0 mg/L (3.7-4.4) and 1.0 mg/L (0.9-1.2) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.41 (0.39-0.42). The concentrations after an ertapenem 1 g dose achieved in cancellous and cortical bone tissue and in synovial tissue were greater than the MIC(90)s for most aerobic organisms for 24 h, and for 12 to 24 h for anaerobic bacteria in healthy volunteers undergoing total hip replacement.