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Prospective surveillance of antibiotic-associated coagulopathy in 970 patients
T H Grasela1, C A Walawander, L S Welage
1Pharmacoepidemiology Research Center, Millard Fillmore Hospital, Buffalo, New York.
Abstract:
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.
Insights
Antibiotic-associated coagulopathy is rare, even with N-methyl-thio-tetrazole (NMTT) containing drugs. The combination of aminoglycoside and antianaerobic (AG + AA) antibiotics showed a slightly higher risk in patients with liver or kidney issues.
Area of Science:
- Pharmacology
- Hematology
- Infectious Diseases
Background:
- N-methyl-thio-tetrazole (NMTT) is a suspected cause of antibiotic-associated coagulopathy.
- The actual frequency and risk factors for this condition require further investigation.
Purpose of the Study:
- To assess the frequency of antibiotic-associated coagulopathy.
- To evaluate the role of NMTT-containing antibiotics versus other regimens.
- To identify risk factors associated with coagulopathy.
Main Methods:
- Nationwide surveillance of 970 patients receiving antibiotics for treatment or prophylaxis.
- Comparison of NMTT-containing cefotetan with non-NMTT antibiotics (cefoxitin, cefazolin) and an aminoglycoside-antianaerobic (AG + AA) combination.
- Measurement of prothrombin time (PT) and partial thromboplastin time (PTT) before and after antibiotic administration.
Main Results:
- Overall hypoprothrombinemia (4.5%) and bleeding (1.7%) were infrequent.
- The AG + AA combination showed a statistically higher incidence of coagulopathy (p < 0.05).
- Liver disease and renal dysfunction were identified as risk factors for hypoprothrombinemia.
Conclusions:
- Antibiotic-associated coagulopathy occurs infrequently in non-critically ill, well-nourished patients.
- The AG + AA combination poses a slightly elevated risk compared to other tested antibiotic regimens.
- NMTT itself does not appear to be a significant independent risk factor in this patient population.