Penetration of piperacillin/tazobactam (4 g/500 mg) into synovial tissue

The degree of penetration of an antibiotic into the infected site is an important criterion for therapeutic success. This is particularly true for bone and joint infections. The association of piperacillin and tazobactam has been widely used in the treatment of serious infections including bone infections, but no study has been devoted to the subject of its diffusion into synovial tissue. Our objective was to quantify piperacillin/tazobactam synovial tissue penetration and to estimate the efficacy of the association against the microorganisms usually encountered in joint infections. In an open-label study, 6 subjects with similar age, weight, height and creatinine clearance, who were undergoing elective total hip replacement, received a single, parenteral, 4 g/500 mg dose of piperacillin/tazobactam. Plasma and synovial tissue samples were collected and analyzed by a validated HPLC method. The mean concentrations of piperacillin and tazobactam 1.5 h after the initiation of infusion were 69.9 +/- 4.9 microg/mL and 7.7 +/- 0.3 microg/mL, respectively, in plasma and 37.1 +/- 2.1 microg/g and 2.8 +/- 0.4 microg/g, respectively, in synovial tissue. The synovial tissue/plasma ratios were 0.5 +/- 0.0 for piperacillin and 0.4 +/- 0.0 for tazobactam. The piperacillin/tazobactam ratios were 9.1:1 in plasma and 13.5:1 in synovial tissue. The concentrations achieved in synovial tissue are above the MICs of most of the susceptible pathogens usually involved in joint infections, which suggests that the piperacillin/tazobactam combination should be effective in the treatment of most joint infections caused by susceptible microorganisms.