Comparison of the effects of mezlocillin, carbenicillin, and placebo on normal hemostasis

Abstract

Mezlocillin was compared with carbenicillin and 0.9% NaCl as placebo in a double-blind manner to determine its effect in vivo on hemostasis in normal volunteers. Eighteen subjects were randomized to receive mezlocillin, 4 g every 6 h; carbenicillin, 7.5 g every 6 h; or placebo, 50 ml every 6 h, each given for 20 intravenous doses unless the template bleeding time after 10 doses was greater than 15 min. Template bleeding times were determined before the dose 1 and 1 h after doses 10 and 20. Five of six (83%) subjects receiving carbenicillin developed template bleeding time prolongation to greater than 21 min, and two of six (33%) subjects receiving mezlocillin and one of six (17%) subjects receiving carbenicillin had mild template bleeding time prolongations of less than 13 min. Coagulation studies (prothrombin time, partial thromboplastin time, and thrombin time) were normal in all subjects, and blood salicylate levels were negative. Thus, in standard therapeutic doses, mezlocillin was less likely than carbenicillin to prolong the template bleeding time above normal (P = 0.04) and, when prolongation occurred with mezlocillin, it was mild. These data support the selective use of mezlocillin in patients at increased risk for bleeding and who require therapy with an antipseudomonal penicillin.