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

Background: The difference in type of antibiotics and susceptibility of Bacteroides fragilis 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 B fragilis is susceptible (BL sus , FQ sus ) and those to which it is not (BL non , FQ non ) and into those given orally (BL po , FQ po ) or intravenously (BL iv , FQ iv ). 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 iv was higher than in BL iv (95% CI: 1.59-46.5). The proportions with an INR ratio of >1.5 in BL sus and FQ sus were higher than in BL non (1.72-14.1) and FQ non (1.05-9.36), respectively. ΔINR values in FQ po , FQ iv , and FQ sus were higher than those in BL po , BL iv , and FQ non , respectively. Conclusions and Relevance: Concomitant use of FQs, or of antibiotics to which B fragilis is susceptible is associated with higher risk of excessive anticoagulation. These findings would contribute to safe and proper antibiotic treatment in warfarin users.