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[Hemostasis disturbance caused by cephalosporins with an N-methylthiotetrazole side chain. A randomized pilot study]
1Institut für Medizinische Biometrie und Informatik, Universität Heidelberg.
Abstract:
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.
Insights
N-methylthiotetrazole (NMTT) cephalosporins can cause hypoprothrombinemia by inhibiting vitamin K epoxide reductase. Monitoring prothrombin time is crucial in older patients receiving these antibiotics.
Area of Science:
- Pharmacology
- Biochemistry
- Clinical Medicine
Background:
- Hypoprothrombinemia is a potential side effect of certain cephalosporins.
- The N-methylthiotetrazole (NMTT) side chain is implicated in this adverse effect.
Purpose of the Study:
- To investigate the mechanism of hypoprothrombinemia induced by NMTT-containing cephalosporins.
- To evaluate the role of vitamin K metabolism in this process.
Main Methods:
- A randomized pilot clinical trial involving 14 hospitalized patients aged 50 years or older with urinary tract infections.
- Patients received latamoxef, cefoperazone, or cefotaxime (control) for 7 days.
- Prothrombin time, PIVKA II, and vitamin K1 2,3-epoxide levels were monitored.
Main Results:
- Two patients on cefoperazone showed increased prothrombin time and PIVKA II.
- Both cefoperazone and latamoxef induced vitamin K1 2,3-epoxide, indicating inhibition of vitamin K epoxide reductase.
- Cefotaxime did not cause these effects.
- Patients with elevated vitamin K1 2,3-epoxide also showed increased endogenous plasma vitamin K levels.
Conclusions:
- NMTT-cephalosporins inhibit hepatic vitamin K epoxide reductase, contributing to hypoprothrombinemia.
- Prothrombin time should be monitored in elderly patients treated with these antibiotics.
- The observed increase in endogenous vitamin K requires further investigation.