Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status

The mechanism of cephalosporin-induced hypoprothrombinemia has been investigated in hospitalized patients, with respect to cephalosporin structure, vitamin K metabolism, and vitamin K status. Cephalosporins containing side chains of N-methylthiotetrazole (latamoxef, cefmenoxime, cefoperazone, cefotetan, cefamandole) or methyl-thiadiazole (cefazolin) all caused the transient plasma appearance of vitamin K1 2,3-epoxide in response to a 10-mg intravenous dose of vitamin K1, whereas two cephalosporins without a heterocyclic side chain (cefotaxime and cefoxitin) did not. The plasma accumulation of vitamin K1 2,3-epoxide was qualitatively similar to, but quantitatively less than, that produced by the oral anticoagulant phenprocoumon. Patients eating normally had plasma vitamin K1 concentrations (176 to 1184 pg/mL) that were within the normal range (150 to 1550 pg/mL) and their clotting tests remained consistently normal for all antibiotics tested. Patients on total parenteral nutrition had lower plasma vitamin K1 concentrations (50 to 790 pg/mL) but normal clotting before starting antibiotic therapy. Of 19 parenterally fed patients, all seven treated with latamoxef developed hypoprothrombinemia, PIVKA-II and a decrease of protein C within four days whereas 12 patients treated with cefotaxime or cefoxitin showed no clotting changes. Latamoxef-associated hypoprothrombinemia was readily reversible by 1 mg of vitamin K1 given intravenously, but hypoprothrombinemia and sub-normal plasma vitamin K1 could recur within two to three days. The data suggest that NMTT-cephalosporins are inhibitors of hepatic vitamin K epoxide reductase and that a lower nutritional-vitamin K status predisposes to hypoprothrombinemia.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. H. Chung and K. Watson Cefazolin-induced hypoprothrombinemia Am. J. Health Syst. Pharm., May 1, 2008; 65(9): 823 - 826. [Abstract] [Full Text] [PDF]

				A S. Mathis, N. Dave, N. K Shah, and G. S Friedman Bleeding and Thrombosis in High-Risk Renal Transplantation Candidates Using Heparin Ann. Pharmacother., April 1, 2004; 38(4): 537 - 543. [Abstract] [Full Text] [PDF]

				D. R. J. Kuypers and K. Claes Intracerebral haemorrhage caused by cefazoline-induced hypoprothrombinaemia in a renal transplant recipient Nephrol. Dial. Transplant., March 1, 2002; 17(3): 532 - 533. [Full Text] [PDF]

				C. W. Kaiser, J. D. McAuliffe, R. J. Barth, and J. A. Lynch Hypoprothrombinemia and Hemorrhage in a Surgical Patient Treated With Cefotetan Arch Surg, April 1, 1991; 126(4): 524 - 525. [Abstract] [PDF]