34th Annual Meeting of the European Bone and Joint Infection Society (EBJIS) 10-12 September 2015 | Estoril, Portugal

IN-VIVO GENTAMICIN CONCENTRATIONS IN PLASMA AND DRAIN FLUID AFTER BONE DEFECT RECONSTRUCTION USING A GENTAMICIN-ELUTING BONE GRAFT SUBSTITUTE P. Horstmann1, W. Hettwer1, Z. Song2 and M. Petersen1

1Department of Orthopedic Surgery, Muskuloskeletal Tumor Section, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark 2Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Orthopaedic Proceedings, vol. 97-B no. SUPP 16 103 (2015) Abstract To document early in-vivo concentrations of gentamicin in plasma and drain fluid after bone defect reconstruction using a gentamicin-eluting bone graft substitute. Introduction Reconstruction of bone defects after surgical bone tumor resection is associated with an increased risk of infection and some surgeons therefore prefer extended antibiotic prophylaxis in these patients. A gentamicin-eluting bone graft substitute consisting of sulphate and apatite has been shown to be effective for treatment of osteomyelitis (1) and may be a valuable addition to the therapeutic and/or prophylactic antibiotic regime for this and many other indications. We performed a prospective pilot study from December 2014 to February 2015 in 7 patients (M/F: 4/3, mean age 51 (37–79) years) who underwent bone defect reconstruction with a gentamicin-eluting bone graft substitute (CERAMENT™|G – BONESUPPORT AB) containing 175 mg gentamicin per 10 mL. Indications for surgery were metastatic bone disease (n=3, proximal humerus), giant cell tumor (n=2, distal femur), aseptic prosthetic loosening (n=1, knee) and chondroid tumor (n=1, distal femur). Additional endoprosthetic reconstruction with a tumor prosthesis was performed in 3 patients (2 proximal humerus and 1 distal femur). Drain fluid and plasma was collected immediately postoperatively and each postoperative day until the drain was removed. In 2 cases we were unable to collect drain fluid directly postoperatively due to minimal fluid production. Gentamicin concentrations were analyzed using an antibody technique (Indiko™ – Thermo Scientific). A mean of 14 (10–20) mL gentamicin-eluting bone graft substitute was used, either alone or in combination with cancellous allograft and/or a bone graft substitute not containing gentamicin (CERAMENT™|BVF – BONESUPPORT AB). Mean drain fluid concentrations of gentamicin were 1200 (723–2100) mg/L immediately postoperative (0–2 hours), 1054 (300–1999) mg/L on day 1 (17–23 hours) and 509 (38–1000) mg/L on day 2 (39–45 hours). Mean plasma concentrations of gentamicin were 1.26 (1.08–1.42) mg/L immediately postoperative, 0.95 (0.25–2.06) mg/L on day 1 and 0.56 (0.20–0.88) mg/L on day 2.

Discussion. As gentamicin induces a concentration-dependent bacterial killing effect, the obviously high local peak concentrations of gentamicin found in this study would be expected to deliver a substantial prophylactic effect after long operations with an increased risk of intraoperative bacterial contamination. Local implantation of a gentamicin-eluting bone graft substitute for bone defect reconstruction results in high concentrations of gentamicin in the drain fluid in the first postoperative days and low plasma concentrations.