Association Between the Prothrombin Time-International Normalized Ratio and Concomitant Use of Antibiotics in Warfarin Users: Focus on Type of Antibiotic and Susceptibility of to Antibiotics.

Background: The difference in type of antibiotics and susceptibility of to antibiotics may influence warfarin anticoagulation. However, these influences have not been clarified in clinical settings.

Objectives: This study aimed to investigate association the between the prothrombin time-international normalized ratio (PT-INR) and concomitant use of antibiotics in a real-world population of warfarin users.

Methods: This was a single-center cohort study using data from health records and included patients who received β-lactams (BLs)/fluoroquinolones (FQs) during ongoing warfarin treatment (2011-2015) at Hamamatsu University Hospital in Japan. Antibiotics were categorized into those to which is susceptible (BL, FQ) and those to which it is not (BL, FQ) and into those given orally (BL, FQ) or intravenously (BL, FQ). Outcomes were excessive PT-INR and changes in PT-INR, defined as the ratio (INR ratio) and difference (ΔINR) of maximum PT-INR and baseline PT-INR. Excessive PT-INR was graded as INR ratio of >1.5 or >2.5.

Results: A total of 1185 warfarin users were included. The proportion of INR ratio >2.5 in FQ was higher than in BL (95% CI: 1.59-46.5). The proportions with an INR ratio of >1.5 in BL and FQ were higher than in BL (1.72-14.1) and FQ (1.05-9.36), respectively. ΔINR values in FQ, FQ, and FQ were higher than those in BL, BL, and FQ, respectively.

Conclusions And Relevance: Concomitant use of FQs, or of antibiotics to which is susceptible is associated with higher risk of excessive anticoagulation. These findings would contribute to safe and proper antibiotic treatment in warfarin users.