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

Background:The difference in type of antibiotics and susceptibility ofBacteroides fragilisto 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 beta-lactams (BLs)/fluoroquinolones (FQs) during ongoing warfarin treatment (2011-2015) at Hamamatsu University Hospital in Japan. Antibiotics were categorized into those to whichB fragilisis susceptible (BLsus, FQ(sus)) and those to which it is not (BLnon, FQ(non)) and into those given orally (BLpo, FQ(po)) or intravenously (BLiv, FQ(iv)). Outcomes were excessive PT-INR and changes in PT-INR, defined as the ratio (INR ratio) and difference (Delta INR) 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 BLiv(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 BLnon(1.72-14.1) and FQ(non)(1.05-9.36), respectively. Delta INR values in FQ(po), FQ(iv), and FQ(sus)were higher than those in BLpo, BLiv, and FQ(non), respectively.Conclusions and Relevance:Concomitant use of FQs, or of antibiotics to whichB fragilisis susceptible is associated with higher risk of excessive anticoagulation. These findings would contribute to safe and proper antibiotic treatment in warfarin users.