Penetration of piperacillin-tazobactam into cancellous and cortical bone tissues

Abstract

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

Adjuvant arthritis-induced changes on ampicillin binding in serum and tissues under the influence of non-steroidal anti-inflammatory drugs in rats

“…As far as bone infection is concerned, it is important in establishing the therapeutic approach to obtain efficient concentrations of the drug in the bone mass. As reported in the literature, cancellous bone has more possibilities of being accessed by penicillins [32]. Our findings are in agreement with those studies reporting that antibiotic concentrations are higher in cancellous than in cortical bone tissue, as determined in the case of the femur compared to the mandible [33].…”

Concentrations of piperacillin–tazobactam in human jaw and hip bone

“…Although the tissue penetration of piperacillinetazobactam has been extensively studied (Wise et al, 1991;Kinzig et al, 1992;Sörgel and Kinzig, 1993;Incavo et al, 1994;Dalla Costa et al, 1997;Boselli et al, 2001;Boselli et al, 2002;Trittler et al, 2002;Tomaselli et al, 2003), data on bone concentrations are available only from two studies (Incavo et al, 1994;Boselli et al, 2001). In both studies iliac crest bone from patients undergoing hip replacement surgery was used.…”

“…The activity of piperacillinetazobactam covers most of the relevant pathogens in the polymicrobial infections of the head and neck (Aldridge, 1994). From the pharmacokinetic point of view concentrations of piperacillinetazobactam in bone have been studied for hip bone of mostly cancellous structure (Incavo et al, 1994;Boselli et al, 2001). However, due to the different histologic and mechanical characteristics of jaw bone, the pharmacokinetic results might not be directly transferable.…”

Antibiotic penetration into bone and joints: An updated review

“…A dose of 4.5 g of piperacillin/tazobactam (4/0.5 g) reached mean bone concentrations of 17.1/2.3 AE 22/2.5 mg/mL with a mean ratio to serum concentration of 0.15 for piperacillin and 0.13 for tazobactam (Al-Nawas et al, 2008). Another study in ten THA patients given 3.375 g (3/0.375 g) dose preoperatively showed mean concentrations of piperacillin in cancellous and cortical bones of 40.5 AE 19.2 and 35.5 AE 14.8 mg/mL, respectively (Incavo et al, 1994). In synovial fluid, 1 h after dosing of 4.5 g in six healthy participants resulted in mean concentrations of 69.9 AE 4.9 and 7.7 AE 0.3 mg/mL for piperacillin and tazobactam, respectively (Boselli et al, 2002).…”