1-n-methyl-5-thiotetrazole and Bacterial-Infections

A prospective surveillance program was initiated to determine the relative role of antibiotics containing N-methylthiotetrazole (NMTT) versus patient risk factors in producing antibiotic-associated bleeding. Five hundred forty-six critically ill patients with serum albumin 30 g/L or below were evaluated for evidence of a bleeding event as documented by clinical observation, hemoglobin changes, and transfusions. Bleeding events occurred in 16% of patients receiving an aminoglycoside combination, 10% receiving antibiotics with the NMTT side chain, and 14.5% receiving antibiotics not containing NMTT (p greater than 0.05). The bleeding rate was highest in febrile patients with cancer (14.5%) and lowest in those with a suspected or documented abdominal infection (10%) (p = 0.04), but within each patient group there was no difference among the antibiotics. We conclude that the use of NMTT-containing antibiotics is not an independent risk factor for bleeding, but the role of severity of illness may be underappreciated.

Topics: Abdomen; Adolescent; Adult; Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Critical Illness; Fever; Hemorrhage; Humans; Neoplasms; Prospective Studies; Risk Factors; Serum Albumin; Tetrazoles

The reported high incidence of vitamin-K-reversible hypoprothrombinemia associated with the new beta-lactamase-stable cephalosporins prompted us to evaluate the effect on hemostasis of three cephalosporins (cefamandole, ceftriaxone, and ceftazidime) in 30 patients with serious infections. Cefamandole and ceftriaxone, both containing a sulfhydryl group, induced a significant and similar prolongation of prothrombin time and decrease in factor VII activity. Ceftazidime, in contrast, had no effect on these two parameters.

Topics: Azoles; Bacterial Infections; Cephalosporins; Female; Humans; Hypoprothrombinemias; Male; Prothrombin Time; Structure-Activity Relationship; Tetrazoles

Antibiotic therapy, using penicillins or cephalosporins, is frequently required in patients on maintenance hemodialysis. Points to consider are dose adjustment for drugs which are excreted via the kidney, drug dialysability, and cumulation with frequent occurrence of side reactions, neurotoxicity and bleeding being the clinically most important ones. For third-generation cephalosporins with N-methylthiotetrazole side chain, impaired intrahepatic vitamin K metabolism may cause problems of hemostasis which can be avoided by dose adjustment and prophylactic administration of vitamin K1.

Topics: Bacterial Infections; Body Weight; Cephalosporins; Dose-Response Relationship, Drug; Drug Administration Schedule; Hemorrhage; Humans; Kidney Failure, Chronic; Kinetics; Penicillin Resistance; Penicillins; Renal Dialysis; Tetrazoles; Vitamin K 1

During the period February 1980-March 1982, clinical evaluation was carried out on 23,855 cases given cefmetazole (CMZ) in 3,916 medical treatment centres in Japan. The drug was found to have superior efficacy and to be of value for all age groups, ranging from infants and small children to the elderly, in infections due to Gram-positive cocci, Gram-negative bacilli and anaerobic bacteria sensitive to this drug. Experiments were also conducted to elucidate the mechanism of development of the disulfiram-like reaction found in cephems with a methyltetrazolylthiomethyl group at the 3 position, i.e., cefmetozole (CMZ), cefoperazone (CPZ) and latamoxef (LMOX). These experiments provided clear evidence that the reaction is due to a rise in the blood concentration of acetaldehyde, as a result of inhibition of acetaldehyde dehydrogenase activity caused by these cephems. The extent of increase in the blood concentration of AcH is proportional to the urinary excretion rate of mercaptomethyltetrazole (Me-TZ), being in the order CPZ greater than LMOX greater than CMZ. This order is believed to be due to the extent of distribution in bile by various antibiotics and to their stability in the tissue fluids.

Topics: Adolescent; Adult; Aged; Aging; Aldehyde Oxidoreductases; Animals; Azoles; Bacterial Infections; Cefmetazole; Cefoperazone; Cephamycins; Child; Child, Preschool; Chromatography, High Pressure Liquid; Dogs; Drug Evaluation; Ethanol; Humans; In Vitro Techniques; Infant; Japan; Macaca fascicularis; Male; Middle Aged; Moxalactam; Rats; Rats, Inbred Strains; Respiratory Tract Infections; Structure-Activity Relationship; Tetrazoles