cefotaxime and Vitamin-K-Deficiency

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

Topics: Cefotaxime; Cholestasis; Humans; Hypoprothrombinemias; Vitamin K Deficiency

Topics: Cefotaxime; Cholestasis; Humans; Hypoprothrombinemias; Vitamin K Deficiency

Recent findings have suggested that the 1-methyltetrazole-5-thiol (MTT) group contained in several beta-lactam antibiotics may be responsible for the hypoprothrombinaemia associated with these drugs. In order to determine if the hypoprothrombinaemia associated with cefazolin is due to the presence of the structurally related 2-methyl-1,3,4,-thiadiazole-5-thiol (MTD) group which it possesses, the ability of MTD and cefazolin to produce hypoprothrombinaemia in rats was examined. Female rats maintained on a vitamin K-deficient diet for ten days developed hypoprothrombinaemia after the intravenous administration of cefazolin for two subsequent days. Hypoprothrombinaemia was also produced by the oral administration to vitamin K-deficient rats of either cefazolin or MTD, while the oral administration of cefotaxime, which does not contain a thiol group, had no effect. In a rat liver microsomal system, MTD was found to be a much more potent inhibitor than cefazolin of the vitamin K-dependent step in clotting factor synthesis, the gamma-carboxylation of glutamic acid. These results suggest that the hypoprothrombinaemia associated with cefazolin may be due to the MTD group.

Topics: Administration, Oral; Animals; Cefazolin; Cefotaxime; Female; Glutamates; Glutamic Acid; Hypoprothrombinemias; Microsomes, Liver; Rats; Rats, Inbred Strains; Thiadiazoles; Vitamin K Deficiency

Various second- and third-generation cephem antibiotics were administered to infants 2 years of age or less. Excluding Streptococcus faecalis, which is resistant to cephems, all of the intestinal bacteria decreased in number, and in many cases these were replaced by yeasts. A positive reaction for protein induced by vitamin K absence or antagonism (PIVKA II) occurred in 25 to 63% of the subjects administered cephems possessing a methylthiotetrazole group, but not in those dosed with cefotaxime or ceftazidime. The effects of cefotaxime and latamoxef (moxalactam) on platelet ADP aggregation were also investigated. When these drugs were administered to clinical patients, moxalactam showed stronger inhibition of aggregation than cefotaxime.

Topics: Adenosine Diphosphate; Anti-Bacterial Agents; Bacteria; Cefotaxime; Child, Preschool; Female; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Intestines; Male; Platelet Aggregation; Vitamin K Deficiency

Fundamental and clinical evaluation of ceftriaxone (CTRX) was performed in the pediatric field and the following results were obtained. The MIC of CTRX against E. coli isolated from urinary tract infections in children ranged from less than or equal to 0.024 to 0.39 mcg/ml except for 1 strain. CTRX was superior to other 3rd generation cephalosporins such as CPZ and LMOX, showing effectiveness also against ABPC-resistant bacteria. The clinical efficacy and bacteriological efficacy in 6 children consisting of 5 with respiratory tract infections and 1 with urinary tract infection were 83% and 100%, respectively. As to the adverse reaction, diarrhea was observed in 2 cases. The determination of PIVKA-II performed during the therapy with CTRX, which is observed when vitamin K is deficient, showed positiveness in 2 cases out of 6 cases including 1 which the clinical efficacy could not be evaluated. The test of platelet function in 3 cases found no inhibition of agglutination. Twice-daily administration with 20 mg/kg CTRX was considered to be a useful and safe method for treatment of bacterial infections in children, although attention should be taken not to cause vitamin K deficiency as in other 2nd and 3rd generation cephalosporins.

Topics: Cefotaxime; Ceftriaxone; Child; Child, Preschool; Drug Evaluation; Female; Humans; Male; Platelet Aggregation; Respiratory Tract Infections; Urinary Tract Infections; Vitamin K Deficiency

To determine whether the hypoprothrombinemia associated with antibiotics containing a 1-methyl-5-thiotetrazole (MTT) group is a result of the presence of the MTT group, rats were maintained on a vitamin K-deficient diet for 10 days and then received either intravenous moxalactam or cefotaxime or oral MTT for two additional days. MTT and moxalactam, which contains the MTT group, prolonged prothrombin time. Cefotaxime, which lacks the MTT group, had no effect.

Topics: Administration, Oral; Animals; Azoles; Cefotaxime; Female; Hypoprothrombinemias; Injections, Intravenous; Moxalactam; Prothrombin Time; Rats; Rats, Inbred Strains; Tetrazoles; Vitamin K Deficiency