Heterogeneity in the treatment of bloodstream infections identified from antibiotic exposure mapping

Abstract

Purpose: As changes in antibiotic therapy are common, intent-to-treat and definitive therapy exposure definitions in infectious disease clinical trials and observational studies may not accurately reflect all antibiotics received over the course of the infection. Therefore, we sought to describe changes in antibiotic therapy and unique treatment patterns among patients with bacteremia. Methods: We conducted a retrospective cohort study of hospitalizations from Veterans Affairs (VA) Medical Centers (January 2002-September 2015) and community hospitals (de-identified Optum Clinformatics DataMart with matched Premier Hospital data; October 2009-March 2013). In the VA population, antibiotic exposures were mapped from the culture collection date among those with positive Staphylococcus aureus cultures. In the Optum-Premier population, exposures were mapped from the admission date among those with a primary diagnosis of bacteremia. Results: Our study included 50 467 bacteremia admissions, with only 14% of admissions having the same treatment pattern as another admission. For every 100 bacteremia admissions, 89 had changes in antibiotic therapy. For every 100 bacteremia admissions with changes in therapy, 95 had unique antibiotic treatment patterns. These findings were consistent in both populations, over time, and among different facilities within study populations. The median time to first therapy change was 2 days after initial therapy, with a median of three changes. Conclusions: Changes in antibiotic therapy for bloodstream infections were nearly universal regardless of hospital setting. Based on our findings, common antibiotic exposure definitions of intent-to-treat and definitive therapy would misclassify exposure in 86% of admissions, which highlights the need for better operational definitions of exposure in infectious diseases research.