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Periprosthetic infection is regarded as one of the most feared complications following total knee arthroplasty, developing in 0.4-2% of patients. Staphylococcus aureus and Staphylococcus epidermidis are credited for more than half of all infections. Cefazolin is the most commonly used antibiotic drug in arthroplasty antibiotic prophylaxis worldwide. Guidelines and studies recommend that prophylactic antibiotics should be completely infused within 60 min before the surgical incision. Cefazolin achieves highest peak bone concentrations 40 min after parenteral application with serum half-life of 108 min and bone half-life of 42 min. Respecting the given pharmacokinetics of cefazolin and theoretical mathematical model we hypothesise that parenteral application of cefazolin should be in time period not longer than 30 min before incision (tourniquet inflation) and not less than 10 min before tourniquet inflation if given in bolus. This new regime would provide maximal blood concentration of the cefazolin and almost maximal bone concentration of the cefazolin at the beginning of the operation and at the beginning of the tourniquet inflation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)