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A prospective randomized trial was conducted comparing the effect of three antibiotics: cefamandole (CM), cefazolin (CZ), and vancomycin (V), used as prophylaxis for prosthetic valve surgery, on the prothrombin (PT) response to warfarin (W) on the third day of anticoagulant therapy. Twenty patients, with normal preoperative PTs, were randomized to each antibiotic. Their PTs were not significantly different at 2 hours after operation and the morning before W was begun. The three groups received similar W doses for 2 days, and the PT, as percentage of activity, on the morning of the third day demonstrated that V (51 +/- 18%) was significantly greater (p less than 0.005) than CM (29 +/- 14%) or CZ (38 +/- 18%). CM had a significantly greater percentage of change in PT (64 +/- 14%, p less than 0.0001) from the first to third day than either CZ (51.1 +/- 18%) or V (44.6 +/- 19%). CM also had a greater number of patients (6) with PTs greater than or equal to 30 seconds on day 3 than either CZ (1) or V (1). The antibiotic influence on the PT response to W in this study is ranked as CM greater than CZ greater than V.

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