[Antibiotic-loaded bone cements: from laboratory studies clinical evaluation]

Abstract

Antibiotic-loaded bone cements (ALBC) were initially used empirically, both for the treatment of infected prostheses and for antibioprophylaxis. We conducted in vitro and animal studies as a prerequisite for proper clinical evaluation. We measured gentamicin diffusion from methacrylate bone cement, and found that the concentration in surrounding fluid was significantly above the minimal inhibitory concentration (MIC). We then implanted ALBC in the proximal femora of 100 ewes, in conditions close to those of total hip replacement (THR). Antibiotic concentrations in bone were above 4 x MIC for more than 6 months. We subsequently measured antibiotic concentrations in drainage fluid, blood and urine samples from 50 patients undergoing THR. Concentrations were over 20 x MIC in periprosthetic fluid, but were below the detection limit in blood after 24 hours and in urine after one week. The blood concentration was less than 1 mg/l--far below the ototoxic and nephrotoxic threshold (8 mg/l). Having established antibiotic bioavailability, we then examined the clinical efficacy of ALBC. We participated in several studies, including a French multicentric review of 342 THR procedures (direct and two-stage exchanges). ALBC was beneficial in both settings, with an 85% infection control rate. This included patients with very severe infections (multiresistant strains, severe osteolysis) treated with two-stage exchanges; and moderate infections treated by direct exchange. (This latter procedure offers fewer complications, more durable functional results, a shorter hospital stay and lower treatment costs.) We also used ALBC for antibioprophylaxis in over 2000 THR procedures, and noted no complications. This method is now being assessed in more than 200 000 cases contained in the Swedish THR Register. The experimental methods that we developed (laboratory studies, animal implantation, clinical pharmacokinetics) set the groundwork for clinical studies of gentamicin ABLC, and also allowed us to develop other ALBC formats, containing vancomycin, for example (restricted to salvage therapy). We also used these methods to evaluate antibiotic-loaded bone substitutes (calcium and carbon phosphates), designed not only to control infectious osteitis but also to replace osteolytic bone.