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

Ann Pharmacother. 2021 Feb;55(2):157-164. doi: 10.1177/1060028020940728. Epub 2020 Jul 7.


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 (BLsus, FQsus) and those to which it is not (BLnon, FQnon) and into those given orally (BLpo, FQpo) or intravenously (BLiv, FQiv). 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 FQiv was higher than in BLiv (95% CI: 1.59-46.5). The proportions with an INR ratio of >1.5 in BLsus and FQsus were higher than in BLnon (1.72-14.1) and FQnon (1.05-9.36), respectively. ΔINR values in FQpo, FQiv, and FQsus were higher than those in BLpo, BLiv, and FQnon, 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.

Keywords: antibiotics; clinical database system; drug interaction; warfarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Anticoagulants / administration & dosage*
  • Anticoagulants / therapeutic use
  • Bacterial Infections / drug therapy
  • Bacterial Infections / microbiology
  • Bacteroides fragilis / drug effects
  • Blood Coagulation / drug effects*
  • Cohort Studies
  • Drug Interactions
  • Female
  • Fluoroquinolones / administration & dosage
  • Fluoroquinolones / adverse effects
  • Fluoroquinolones / therapeutic use
  • Hemorrhage / chemically induced
  • Humans
  • International Normalized Ratio*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prothrombin Time*
  • Warfarin / administration & dosage*
  • Warfarin / therapeutic use
  • beta-Lactams / administration & dosage
  • beta-Lactams / adverse effects
  • beta-Lactams / therapeutic use


  • Anti-Bacterial Agents
  • Anticoagulants
  • Fluoroquinolones
  • beta-Lactams
  • Warfarin