• DOI:10.1002/j.1552-4604.1988.tb03106.x
• Corpus ID: 30591177

Mechanism of Cephalosporin‐induced Hypoprothrombinemia: Relation to Cephalosporin Side Chain, Vitamin K Metabolism, and Vitamin K Status

@article{Shearer1988MechanismOC,
  title={Mechanism of Cephalosporin‐induced Hypoprothrombinemia: Relation to Cephalosporin Side Chain, Vitamin K Metabolism, and Vitamin K Status},
  author={Martin J Shearer and Heinrich Bechtold and Konrad Andrassy and Janti Koderisch and Patrick T. McCarthy and Dietmar Trenk and Eberhard J{\"a}hnchen and Eberhard Ritz},
  journal={The Journal of Clinical Pharmacology},
  year={1988},
  volume={28}
}

• M. Shearer, H. Bechtold, +5 authors E. Ritz
• Published 1 January 1988
• Medicine, Biology
• The Journal of Clinical Pharmacology

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.