Risk of bleeding and hypoprothrombinaemia associated with NMTT side chain antibiotics: using cefoperazone as a test case.

A retrospective cohort study was performed to determine the incidence of hypoprothrombinaemia and bleeding in patients receiving cefoperazone, a third-generation cephalosporin that contains an NMTT side chain. 374 patients receiving cefoperazone from February 1983 to March 1986 at a teaching hospital in Philadelphia were compared with 497 patients receiving either ceftizoxime or cefotaxime during the same period, and with 476 patients receiving ceftazidime from April 1985 to December 1987. Adverse events (any bleeding episodes, decrease in haemoglobin, prolongation of prothrombin time (PT), and prolongation of partial thromboplastin times (PTT)) were evaluated, if occurring during the period from the start of cephalosporin therapy, or the start of therapy with one of the two control drugs, for 14 days after the last date of the first course of therapy were recorded. An increased risk of hypoprothrombinaemia was associated with the use of cefoperazone: the prothrombin time was prolonged by 5 s or more in 12.3% of patients receiving cefoperazone vs. 5.8% of patients receiving ceftizoxime or cefotaxime, and vs. 5.8% receiving ceftazidime; the adjusted odds ratios (95% CIs) were 3.6 (1.7-7.4) and 3.8 (1.8-7.8), respectively, and these increased at higher doses of cephalosporin. No protection was apparent from the administration of vitamin K prior to or during the course of cephalosporin. No overall increased risks were observed for bleeding (adjusted odds ratios (95% CIs) were 1.1 (0.8-1.4) vs. ceftizoxime or cefotaxime, and 0.9 (0.6-1.2) vs. ceftazidime), decrease in haemoglobin, or increased partial thromboplastin time. In subgroup analyses, increased risks of bleeding were observed with high dose cefoperazone use [2.8 (1.5-5.5) vs. ceftizoxime or cefotaxime, and 2.3 (1.1-4.6) vs. ceftazidime]. Patients receiving NMTT side chain antibiotics should be monitored for hypoprothrombinaemia, but any increase in bleeding is likely to be small, and prophylactic vitamin K is probably not warranted. Copyright 1999 John Wiley & Sons, Ltd.