Clinical use and safety of a novel gentamicin-releasing resorbable bone graft substitute in the treatment of osteomyelitis/osteitis

Abstract

Objective: A clinical investigation into a new bone void filler is giving first data on systemic and local exposure to the anti-infective substance after implantation.

Method: A total of 20 patients with post-traumatic/post-operative bone infections were enrolled in this open-label, prospective study. After radical surgical debridement, the bone cavity was filled with this material. The 21-day hospitalisation phase included determination of gentamicin concentrations in plasma, urine and wound exudate, assessment of wound healing, infection parameters, implant resorption, laboratory parameters, and adverse event monitoring. The follow-up period was six months.

Results: Systemic exposure to gentamicin after implantation was very low as local gentamicin concentrations were measured in wound exudate after six to ten hours. There were no signs of infectious complication throughout the clinical phase. Four patients had recurrent infections several weeks to months after implantation. The outcome was deemed successful by remission of infection in 16 (80%) of these problematic long-term treated patients. Safety laboratory measurements did not indicate nephrotoxic or hepatotoxic effects.

Conclusions: Local application of calcium sulphate/carbonate bone void filler comprising gentamicin revealed sufficient active local levels of the antibiotic by simultaneous significant low systemic exposure in patients with mostly chronic osteomyelitis/osteitis. The material was safe and well tolerated. Cite this article: Bone Joint Res 2014;3:223-9.

Keywords: Calcium sulfate; Gentamicin; Local antibiotic therapy; Osteomyelitis; Resorbable bone void filler.

Figs. 1a - 1b

Figure 1a – photograph showing in situ demonstration of applied beads in a debrided bone void. Figure 1b – radiograph of the implant’s position in a chronically infected tibial zone.

Figs. 1a - 1b

Figure 1a – photograph showing in situ demonstration of applied beads in a debrided bone void. Figure 1b – radiograph of the implant’s position in a chronically infected tibial zone.

Fig. 2

Graph showing mean (n = 18 to 20) plasma gentamicin concentrations at baseline (0 hours: within six hours prior to surgery) and after implantation of HERAFILL® beads G (Heraeus Medical GmbH) (error bars = standard deviation)

Fig. 3

Graph showing mean (n = 16-20) urine gentamicin concentrations at baseline (0 hours: 24-hour collection within six hours prior to surgery) and after implantation of HERAFILL^® beads G (Heraeus Medical GmbH) (error bars = standard deviation)

Fig. 4

Graph showing mean (n = 18 to 20) gentamicin concentrations in wound-exudate at baseline (0 hours: sample taken during surgery) and after implantation of Herafill^® beads G (Heraeus Medical GmbH) (error bars = standard deviation)

Figs. 5a - 5d

Radiographs showing HERAFILL® beads G (Heraeus Medical GmbH) after implantation into a distal tibial bone void a) pre-operatively, b) post-operatively, c) three and d) six months post-operatively.

Figs. 5a - 5d

Radiographs showing HERAFILL® beads G (Heraeus Medical GmbH) after implantation into a distal tibial bone void a) pre-operatively, b) post-operatively, c) three and d) six months post-operatively.

Figs. 5a - 5d

Radiographs showing HERAFILL® beads G (Heraeus Medical GmbH) after implantation into a distal tibial bone void a) pre-operatively, b) post-operatively, c) three and d) six months post-operatively.

Figs. 5a - 5d

Radiographs showing HERAFILL® beads G (Heraeus Medical GmbH) after implantation into a distal tibial bone void a) pre-operatively, b) post-operatively, c) three and d) six months post-operatively.