Desirability of Outcome Ranking and Response Adjusted for Antibiotic Risk (DOOR/RADAR) Post Hoc Analysis Supports Equipoise for Antibiotic Initiation Strategies in Intensive Care Unit-Acquired Pneumonia.

Abstract

Background: Pneumonia is the most common intensive care unit (ICU)-acquired infection and source of potential sepsis in ICU populations but can be difficult to diagnose in real-time. Despite limited data, rapid initiation of antibiotic agents is endorsed by society guidelines. We hypothesized that a post hoc analysis of a recent randomized pilot study would show no difference between two antibiotic initiation strategies. Patients and Methods: The recent Trial of Antibiotic Restraint in Presumed Pneumonia (TARPP) was a pragmatic cluster-randomized pilot of antibiotic initiation strategies for patients with suspected ICU-acquired pneumonia. Participating ICUs were cluster-randomized to either an immediate initiation protocol or a specimen-initiated protocol where a gram stain was required for initiation of antibiotics. Patients in the study were divided into one of seven mutually exclusive outcome rankings (desirability of outcome ranking; DOOR): (1) Survival, No Pneumonia, No adverse events; (2) Survival, Pneumonia, No adverse events; (3) Survival, No Pneumonia, ventilator-free-alive days ≤14; (4) Survival, Pneumonia, ventilator-free-alive days ≤14; (5) Survival, No Pneumonia, Subsequent episode of suspected pneumonia; (6) Survival, Pneumonia, Subsequent episode of suspected pneumonia; and (7) Death. These rankings were further refined using the duration of antibiotics prescribed for pneumonia (response adjusted for antibiotic risk; RADAR). Results: There were 186 patients enrolled in the study. After applying the DOOR analysis, a randomly selected patient was equally likely to have a better outcome in specimen-initiated arm as in the immediate initiation arm (DOOR probability: 50.8%; 95% confidence interval [CI], 42.7%-58.9%). Outcome probabilities were similar after applying the RADAR analysis (52.5%; 95% CI, 44.2%-60.6%; p = 0.31). Conclusions: We found that patients for whom antibiotic agents were withheld until there was objective evidence (specimen-initiated group) had similar outcome rankings to patients for whom antibiotic agents were started immediately. This supports the findings of the TARPP pilot trial and provides further evidence for equipoise between these two treatment strategies.