Population pharmacokinetics of cefuroxime and uptake into hip and spine bone of patients undergoing orthopaedic surgery

Abstract

Objectives:

To reduce the incidence of peri- or postoperative infections in orthopaedic surgery, patients are prophylactically treated with antibiotics. Here, we wanted to know whether effective bone and intervertebral disc concentrations of cefuroxime are reached. Methods:

Patients undergoing surgery of hip (N = 40; 62.5% male) or spine (N = 40; 55% male) were pretreated with 1.5 g of the second-generation cephalosporin cefuroxime before surgery. We studied plasma population kinetics and bone and intervertebral disc (C5/6 till L5/S1) concentrations of cefuroxime using high-performance liquid chromatography. Key findings:

The plasma kinetics of cefuroxime in 80 patients was analysed using a population approach. The clearance amounted to 7.86 l/h. The peripheral and central volumes of distribution were estimated as 8.45 and 10.4 l, respectively. The concentrations in hip samples amounted to 9.8 ± 0.6 µg/g in cancellous bone and 8.9 ± 0.8 µg/g in cortical bone. Cefuroxime concentrations in vertebral bone and intervertebral discs were calculated as 9.6 ± 1.3 and 8.9 ± 1.1 µg/g, respectively. Conclusion:

Even if a majority of patients undergoing hip or spine surgery probably achieved adequate concentrations of cefuroxime, not all patients reached bone concentrations of cefuroxime above a recommended breakpoint for susceptible germs at the time of surgery.