Comparison of three methods of antibiotic prophylaxis in knee arthroplasty

Prophylactic intravenous cefamandole nafate was administered by the systemic, systemic with probenecid (causing renal tubular blockade of antibiotic excretion), and intravenous regional routes. Bone antibiotic levels were assayed 15 minutes and 12 hours after administration, and hematoma concentrations after 8 hours. Bone concentrations after intravenous regional administration were significantly greater than systemic after 15 minutes, but were not detectable after 12 hours. Probenecid produced inhibitory concentrations in bone after 12 hours and also increased hematoma antibiotic concentrations to three times those achieved by systemic administration. Adequate prophylaxis may be possible with two rather than three doses of cefamandole if probenecid is used.