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

Using a new rabbit model of methicillin-susceptible Staphylococcus aur eus knee prosthesis infection, we compared the efficacies of sparfloxa cin (50 mg/kg of body weight subcutaneously, twice a day) and pefloxac in (50 mg/kg subcutaneously, twice a day), A partial knee replacement was performed with a silicone implant fitted into the intramedullary c anal of the tibia, and 5 x 10(7) CFU of methicillin-susceptible S. aur eus was injected into the knee, The 7-day treatment regimen was starte d 15 days later. The MICs and MBCs of sparfloxacin and pefloxacin were , respectively, 0.06 and 0.25 mu g/ml (MIC) and 0.25 and 1 mu g/ml (MB C), The peak levels of sparfloxacin and pefloxacin in serum were 3.6 a nd 21 mu g/ml, respectively, Three weeks after the end of treatment, a nimals were sacrificed and tibias were removed, pulverized, and quanti tatively cultured, In contrast to pefloxacin (3.61 +/- 1.64 log(10) CF U/g of bone), sparfloxacin significantly reduced the bacterial density (2.12 +/- 1.1 log(10) CFU/g of bone) (P = 0.01) in comparison with th e level in controls (4.59 +/- 1.21 log(10) CFU/g of bone), without sel ection of resistant variants, Sparfloxacin was significantly more effe ctive than pefloxacin (P = 0.025), The autoradiographic pattern of [C- 14] sparfloxacin diffusion was studied in noninfected animals with pro stheses and in infected animals 15 days after inoculation, Sixty minut es after completion of infusion of 250 mu Ci of [C-14]sparfloxacin, in infected animals the highest levels of radioactivity were detected ar ound the prosthesis, in femoral cartilage, and in articular ligaments, Radioactivity was slightly less intense in bone marrow and muscles an d was very weak in compact bone, The distribution of sparfloxacin in u ninfected rabbits was similar, Thus, sparfloxacin may represent a vali d alternative therapy in these infections provided that it is carefull y monitored for potential side effects.