Time to Appropriate Therapy and Antimicrobial Resistance-Attributable Mortality

To the Editor—We read with great interest the article by Brown et al, “The Burden of Antimicrobial Resistant Bacteremia in Ontario: A Population-Wide Analysis of Attributable Mortality From 110 Pathogen-Antibiotic Combinations” [1]. The authors compared 30-day mortality between bacteremia caused by antimicrobial susceptible and antimicrobial resistant pathogens, and quantified the attributable impact of antimicrobial resistance (AMR). The rigorous adjustment for important confounders, including age, frailty, and comorbidities, is a notable strength of this study. We would, however, like to highlight an important consideration for interpretation of the findings. The time from onset of bacteremia to initiation of appropriate antimicrobial therapy was not included as an adjustment variable. Prior study by Kumar et al [2] demonstrated that, among patients with septic shock, each 1-hour delay in the administration of appropriate antimicrobial therapy after shock onset was associated with a 7.6% decrease in survival. Time to appropriate antimicrobial therapy is therefore a critical determinant of outcomes in severe infections. Because this factor was not accounted for in the adjusted analyses, it remains possible that delay in initiation of appropriate therapy contributed substantially to 30-day mortality. Consequently, the independent effect of AMR on mortality may have been overestimated.