cefotaxime and Blood-Coagulation-Disorders

The mechanism of hypoprothrombinemia induced by cephalosporins containing the N-methylthiotetrazole (NMTT) side chain has been investigated in a randomized clinical, trial (pilot study) with 14 hospitalized patients (main inclusion criteria: age greater than or equal to 50 years, urinary tract infection, normal prothrombin time. Therapy groups: latamoxef (n = 5), cefoperazone (n = 5), cefotaxime (control, n = 4). Duration of treatment: 7 days). Two patients under cefoperazone exhibited a significant increase of prothrombin time, accompanied by the appearance of PIVKA II (prothrombin induced in vitamin K absence). Both cefoperazone (in 4 patients) and latamoxef (in 3 patients) caused the appearance of endogenous vitamin K1 2,3-epoxide, whereas cefotaxime did not. This confirms the hypothesis that NMTT-cephalosporins are inhibitors of hepatic vitamin K epoxide reductase, and that this is at least partly responsible for the clinically observed hypoprothrombinemia. In older patients treated with these antibiotics, prothrombin time should be controlled before as well as under therapy. Unexpectedly, the patients displaying an appearance of vitamin K1 2,3-epoxide showed a statistically significant increase of endogenous plasma vitamin K levels. This effect needs further investigation.

Topics: Aged; Aged, 80 and over; Azoles; Blood Coagulation Disorders; Cefoperazone; Cefotaxime; Cephalosporins; Female; Humans; Male; Moxalactam; Pilot Projects; Protein C; Prothrombin Time; Random Allocation; Tetrazoles; Urinary Tract Infections; Vitamin K Deficiency

beta-Lactam antimicrobial agents have until recently enjoyed a reputation of reliability and safety. Now serious problems have emerged associated with use of some of the newer drugs of this class. Latamoxef (moxalactam) and cefoperazone, both of which have a methyltetrazolethiol side chain, have been reported to cause coagulation abnormalities, clinical bleeding, and disulfiram-like reactions. In addition, an unusually high incidence of diarrhoea has been associated with administration of cefoperazone. Cefotaxime does not have the [methylthiotetrazole] side chain and has not caused bleeding, coagulopathy, or disulfiram-like reactions. Diarrhoea, usually mild, has been observed in only 1% of patients given cefotaxime in clinical trials. The remarkable safety record of cefotaxime is an important consideration for clinicians in the selection of an antimicrobial agent for seriously ill patients.

Topics: Anti-Bacterial Agents; Blood Coagulation Disorders; Cefotaxime; Diarrhea; Disulfiram; Humans