N-methyl-thio-tetrazole inhibition of the gamma carboxylation of glutamic acid: possible mechanism for antibiotic-associated hypoprothrombinaemia.

Several new antibiotics which contain an N-methyl-thio-tetrazole side chain have been associated with the development of hypoprothrombinaemia. This side chain was found to be capable of the in-vitro inhibition of a necessary reaction in the synthesis of prothrombin, the gamma carboxylation of glutamic acid. The 50% inhibitory concentration was 1.1 mmol/l. The intact antibiotics latamoxef, cephamandole, and cefoperazone, which contain the side chain, did not inhibit the reaction at concentrations up to 2 mmol/l. These results suggest that hypoprothrombinaemia associated with antibiotics containing N-methyl-thio-tetrazole side chains may be a consequence of the in-vivo degradation of these antibiotics and the subsequent inhibition of the gamma carboxylation of glutamic acid by the side chain.