REGIONAL AND SYSTEMIC PROPHYLAXIS WITH TEICOPLANIN IN MONOLATERAL AND BILATERAL TOTAL KNEE REPLACEMENT PROCEDURES - STUDY OF PHARMACOKINETICS AND TISSUE PENETRATION

Twenty-four patients undergoing monolateral or bilateral total knee replacement (TKR) procedures were randomized to receive teicoplanin (T) either systemically or regionally. Subjects scheduled for systemic prophylaxis and undergoing monolateral (six patients) or bilateral (five patients) TKR received a single 800-mg dose of T in 100 mi of saline as a 5-min infusion into a forearm vein 2.5 h before surgery. For regional prophylaxis, patients undergoing monolateral surgery (eight subjects) received 400 mg of T in 100 mi of saline as a 5-min infusion into a foot vein of the leg to be operated on immediately after the tourniquet was inflated. For the Ave patients scheduled for bilateral operation and regional prophylaxis, the administration of T was also repeated for the second knee operation. The tourniquet, as the standard TKR surgical technique, was inflated to 400 mm Hg (c. 50 kPa) in all 24 patients immediately before the beginning of surgery and kept in place for the duration of the operation. Samples of serum, bone, skin, synovia, and subcutaneous tissue were collected at timed intervals during surgery. They were microbiologically assayed for T by using Bacillus subtilis as the test organism. Overall, the mean T concentrations obtained with regional route prophylaxis were found to be 2 to 10 times higher than those achieved following systemic prophylaxis. Moreover, peak levels in different tissues after regional prophylaxis were significantly higher (P < 0.05). None of the patients experienced adverse effects due to regional or systemic T administration; no prosthetic or wound infections were observed in the follow-up period (from 12 to 26 months).