N-methyl-thio-tetrazole (NMTT) has been proposed as a causative factor in antibiotic-associated coagulopathy. To evaluate this hypothesis, a nationwide surveillance program was initiated to determine the relative frequency of antibiotic-associated coagulopathy and the importance of specific risk factors. A total of 970 patients were studied, with 491 being treated for infections and 479 receiving antimicrobial surgical prophylaxis. The NMTT-containing antibiotic cefotetan was compared with non-NMTT-containing antibiotics, for example, cefoxitin and cefazolin (prophylaxis only), and an aminoglycoside-antianaerobic (AG + AA) combination. Prothrombin time (PT) and partial thromboplastin time (PTT) were measured for each patient prior to the start of antibiotics and within 24-96 hours after the conclusion of drug administration. The patient population was relatively young [mean (SD) age 51.0 (20) yrs] with good nutritional status. The overall frequency of hypoprothrombinemia (4.5%) and bleeding (1.7%) was very low, and was highest with the use of AG + AA (p less than 0.05). No statistical differences were observed for the remaining antibiotic regimens in either the prophylaxis or treatment group. Logistic regression analysis identified treatment with the AG + AA combination, presence of liver disease, and renal dysfunction as factors associated with an increased risk of hypoprothrombinemia. In conclusion, this study suggests that the frequency of antibiotic-associated coagulopathy is low, regardless of antibiotic, in patients who are not critically ill and not malnourished.
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