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Perioperative parenteral cefoxitin was compared with oral erythromycin, neomycin and parenteral cefazolin in a prospective, double-blind, randomized evaluation of 119 patients undergoing colorectal operations. Patients receiving cefoxitin had a higher wound infection rate than patients receiving erythromycin-neomycin-cefazolin (12.5% v 3.2%, respectively, p = .06). A direct correlation existed between the duration of the operation and the infection rate. Cefoxitin prophylaxis was as effective as erythromycin-neomycin-cefazolin in patients undergoing surgical procedures of 4 hours or less (infection rates of 4.8% and 4.0%, respectively). However, for surgical procedures lasting more than 4 hours, 5 of 14 patients (37.5%) receiving cefoxitin developed a wound infection v 0 of 13 patients receiving erythromycin-neomycin-cefazolin (p less than .05). It is speculative as to whether frequent two-gram doses of cefoxitin given during the operation would provide prophylaxis equivalent to erythromycin-neomycin-cefazolin.