The penetration characteristics of piperacillin-tazobactam into cortical and cancellous bone tissues were investigated in 10 patients undergoing total hip replacement. The concentration ratios of piperacillin/ tazobactam were 9.4 ± 1.8 in cancellous bone tissue and 8.0 ± 2.2 in cortical bone tissue, which were close to the 8:1 ratio of drugs administered. The mean ratios of drug concentrations in bone and plasma for cancellous and cortical tissue were 23 and 18%, respectively, for piperacillin and 26 and 22%, respectively, for tazobactam. The concentrations of tazobactam achieved are sufficient to exert anti-j-lactamase activity and supportive of clinical trials involving bone and joint infections, including those caused by P-lactamase-producing pathogens.One important criterion for dose selection of an antibiotic is the degree of penetration to the infected site.Piperacillin sodium has been widely used in the treatment of serious infections, including bone and joint infections (4, 14). Its effect, however, is limited by its susceptibility to 3-lactamase inactivation. Tazobactam (CL 298, produced by piperacillin-resistant isolates, namely, Escherichia coli, Staphylococcus sp., and Bacteroides sp. (6). Since tazobactam rapidly and irreversibly inactivates ,-lactamases, maintenance of concentration above the MIC for most of the dosing interval at the site of infection as required for ,B-lactams may not be necessary. A combination of 3 g of piperacillin and 375 mg of tazobactam (an 8:1 ratio) given every 6 h as monotherapy has been efficacious for treating various infections, including bone and joint infections. This study was undertaken to characterize (i) the concentrations of tazobactam in bone and (ii) the ratio of piperacillin/tazobactam in cortical and cancellous bone tissues.This was a single-dose, open-label, single-arm, noncomparative study. Patients over the age of 18 years and weighing between 45 and 102 kg who were undergoing elective total hip replacement were enrolled in this study after an informed consent was obtained. Patients were excluded if they were allergic to 3-lactam antibiotics or ,-lactamase inhibitors, receiving any other antimicrobial therapy, or exhibited renal dysfunction defined by a creatinine clearance of <40 ml/min or a concentration of creatinine in serum of >2.5 mg/dl. Usual preoperative medications except those known to affect piperacillin-tazobactam disposition (e.g., probenecid) were allowed. Additional antibiotics were allowed after the bone and plasma sampling was completed. Recording of medical history, a physical examination, and clinical laboratory tests were