EFFICACY OF TEICOPLANIN AND AUTORADIOGRAPHIC DIFFUSION PATTERN OF [C-14]TEICOPLANIN IN EXPERIMENTAL STAPHYLOCOCCUS-AUREUS INFECTION OF JOINT PROSTHESES

Prosthesis infections are difficult to cure. Infection with methicilin -resistant staphylococci is becoming more common in patients with orth opedic implants. Using a recently developed model of methicillin-resis tant Staphylococcus aureus (MRSA) infection of a knee prosthesis, we c ompared the efficacies of teicoplanin and vancomycin. [C-14]teicoplani n diffusion in this model was also studied by autoradiography, A parti al knee replacement was performed with a silicone implant fitting into the intramedullary canal of the tibia, and 10(7) CFU of MRSA was inje cted into the knee. Treatment with teicoplanin or vancomycin (20 or 60 mg/kg of body weight, respectively, given intramuscularly twice daily ) was started 7 days after inoculation and was continued for 7 days. T he teicoplanin and vancomycin MICs for MRSA were 1 mu g/ml. Mean peak and trough levels in serum mere 39.1 and 23.5 mu g/ml, respectively, f or teicoplanin and 34.4 and 18.5 mu g/ml, respectively, for vancomycin , Fifteen days after the end of therapy, the animals were killed and t heir tibias were removed, pulverized, and quantitatively cultured. Tei coplanin and vancomycin significantly reduced (P < 0.05) the bacterial density (2.7 +/- 1.3 and 3.3 +/- 1.6 log(10) CFU/g of bone, respectiv ely) compared to those for the controls (5.04 +/- 1.4 log(10) CFU/g of bone). The bacterial covents of teicoplanin- and vancomycin-treated r abbits were comparable, The [C-14]teitoplanin antoradiographic diffusi on patterns in rabbits with prostheses, two of which were uninfected a nd two of which were infected, were studied 15 days after inoculation, Sixty minutes after the end of an infusion of 250 mu Ci of [C-14]teic oplanin, autoradiography showed that in the infected animals, the high est levels of radioactivity were located around the prosthesis and in the periosteum, bone marrow, and trabecular bone. Radioactivity was le ss intense in epiphyseal disk cartilage, femoral cartilage, articular ligaments, and muscles and was weak in compact bone. A similar distrib ution pattern was seen in uninfected rabbits. Thus, teicoplanin may re present an effective alternative therapy for the treatment of these in fections.