Bone, subcutaneous tissue and plasma pharmacokinetics of cefuroxime in total knee replacement patients – a randomized controlled trial comparing continuous and short‐term infusion

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica Vol. 127; no. 12; pp. 779 - 788
• Main Authors: Tøttrup, Mikkel, Søballe, Kjeld, Bibby, Bo M., Hardlei, Tore F., Hansen, Peter, Fuursted, Kurt, Birke‐Sørensen, Hanne, Bue, Mats
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.12.2019
• Subjects: Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Antibiotic Prophylaxis - methods; Antibiotics; Arthroplasty, Replacement, Knee; Biomedical materials; Bone and Bones - metabolism; bone concentrations; Bone surgery; Cancellous bone; Cefuroxime; Cefuroxime - administration & dosage; Cefuroxime - blood; Cefuroxime - pharmacokinetics; continuous infusion; Cortical bone; Drug Administration Schedule; Humans; Infusions, Intravenous; Knee; Male; Microbial Sensitivity Tests; Microdialysis; Middle Aged; Minimum inhibitory concentration; Order parameters; Orthopedics; Parameter estimation; Pharmacokinetics; Pharmacology; population pharmacokinetics; Prophylaxis; Prosthesis-Related Infections - prevention & control; Subcutaneous Tissue - metabolism; Surgical implants; Tissues; cefuroxime; bone concentrations; microdialysis; continuous infusion; population pharmacokinetics
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/apm.12996

Cefuroxime is widely used as antibiotic prophylaxis for orthopaedic procedures. We evaluated bone, subcutaneous tissue (SCT) and plasma pharmacokinetics of cefuroxime in male patients undergoing total knee replacement (TKR) after both traditional short‐term infusion (STI) and continuous infusion (CI). Eighteen male patients undergoing TKR were randomly assigned to STI or CI of 1.5 g of cefuroxime. Measurements were obtained in plasma, SCT, cancellous and cortical bone every 30 min for 8 h following surgery. For sampling in solid tissues, microdialysis was applied. Population pharmacokinetic modelling was performed in order to estimate pharmacokinetic parameters, and to assess the probability of attaining cefuroxime concentrations above clinically relevant minimal inhibitory concentrations (MICs) for 65% and 90% of the 8 h dosing interval. Low SCT and cortical bone penetration were found in both the STI and the CI group, but the findings were only significant in the STI group. Irrespective of MIC, tissue and target, CI leads to improved probability of attaining relevant pharmacokinetic targets compared with STI. For the Staphylococcus aureus MIC breakpoint (4 μg/mL), STI leads to inadequate probability of target attainment. CI of 1.5 g of cefuroxime leads to improved probability of attaining relevant pharmacokinetic targets in male TKR patients compared with traditional STI. These findings suggest that application of CI may improve antibiotic prophylaxis for male TKR patients.