(248) Data mining of adverse reactions of antimicrobial agents leading to coagulation disorders based on FAERS database

Background: With increasing antimicrobial use, there is a mounting apprehension regarding to adverse hematological responses, particularly coagulation disorders. Comprehending the prevalence and implications of coagulation disorders linked to different antibiotics and antifungal agents is imperative for enhancing the decision-making process in anti-infective therapy and safeguarding patient well-being.

Objectives: To explore and analyze adverse drug reaction (ADR) signals related to antimicrobial-induced coagulation disorders and provide reference basis for optimizing treatment regimens.

Methods: Using the FDA Adverse Event Reporting System (FAERS) database and OpenVigil 2.1 data platform, adverse drug reaction (ADR) reports for 68 antimicrobial agents were collected from January 1, 2004, to September 30, 2021. The frequency method detected ADR signals of coagulation disorders induced by antimicrobial agents, which were then ranked by signal intensity.

Results: A total of 17,667 adverse reaction reports were identified, encompassing decreased platelet levels, prolonged prothrombin time (PT), increased international normalized ratio (INR), decreased fibrinogen (Fib) levels, and prolonged activated partial thromboplastin time (aPTT). Using proportional reporting ratio (PRR), signals for adverse reactions were detected across 68 drugs. 37, 35, 33, 28, and 16 drugs exhibited signals for decreased platelet count, increased INR, prolonged PT, prolonged aPTT, and decreased Fib levels, respectively. The top 5drugs causing PRR values of the five coagulation disorders, ranked from highest to lowest, were as follows: (1) decreased PLT: cefoperazone, teicoplanin, tigecycline, piperacillin and cefepime. (2) increase in INR: cefoperazone, teicoplanin, levofloxacin, fluconazole and clarithromycin. (3) prolonged PT: ceftriaxone, cefoperazone, isoniazid, daptomycin and imipenem-cilastatin. (4) prolonged aPTT: cefoperazone, ceftazidime, tigecycline, levofloxacin and imipenem-cilastatin. (5) decreased Fib: tigecycline, piperacillin, ceftriaxone, meropenem and methoxybenzene. Notably, cefoperazone consistently ranked among the top three drugs for all four adverse reactions based on PRR. Moreover, no ADR signals related to coagulation disorders were observed for aminoglycosides, polymyxins, and phosphomycin among the antimicrobial agents assessed.

Conclusions: Coagulation disorders resulting from antimicrobial agents show correlation, with different drugs affecting various coagulation indicators. When selecting antimicrobial agents, consideration should be given to the hematological safety profile of the drugs and careful monitoring is warranted.