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.

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.

Provider Perceptions of Antibiotic Initiation Strategies for Hospital-Acquired Pneumonia.

Background: The practice of rapidly initiating antibiotic therapy for patients with suspected infection has recently been criticized yet remains commonplace. Provider comfort level has been an understudied aspect of this practice. Hypothesis: We hypothesized that there would be no significant differences in provider comfort level between the two treatment groups. Methods: We prospectively surveyed critical care intensivists who provided care for patients enrolled in the Trial of Antibiotic Restraint in Presumed Pneumonia (TARPP), which was a multicenter cluster-randomized crossover trial that evaluated an immediate antibiotic initiation protocol compared with a protocol of specimen-initiated antibiotic initiation in ventilated patients with suspected new-onset pneumonia. At the end of each enrollment arm, physicians at each center were surveyed regarding their overall comfort level with the recently completed treatment arm, and perception of adherence. Both a paired and unpaired analysis was performed. Results: We collected 51 survey responses from 31 unique participants. Providers perceived a higher rate of adherence to the immediate initiation arm than the specimen-initiated arm (Always Adherent: 37.5% vs. 11.1%; p = 0.045). Providers were less comfortable waiting for objective evidence of infection in the specimen-initiated arm than with starting antibiotic agents immediately (Very Comfortable: 83.3% vs. 40.7%; p = 0.004). For the smaller paired analysis, there was no longer a difference in comfort level. Conclusions: There may be differences in provider comfort levels and perceptions of adherence when considering two different antibiotic initiation strategies for suspected pneumonia in ventilated patients. These findings should be considered when planning future studies.

Trial of antibiotic restraint in presumed pneumonia: A Surgical Infection Society multicenter pilot.

BACKGROUND: Pneumonia is the most common intensive care unit-acquired infection in the trauma and emergency general surgery population. Despite guidelines urging rapid antibiotic use, data supporting immediate antibiotic initiation in cases of suspected infection are limited. Our hypothesis was that a protocol of specimen-initiated antibiotic initiation would have similar compliance and outcomes to an immediate initiation protocol. METHODS: We devised a pragmatic cluster-randomized crossover pilot trial. Four surgical and trauma intensive care units were randomized to either an immediate initiation or specimen-initiated antibiotic protocol for intubated patients with suspected pneumonia and bronchoscopically obtained cultures who did not require vasopressors. In the immediate initiation arm, antibiotics were started immediately after the culture regardless of patient status. In the specimen-initiated arm, antibiotics were delayed until objective Gram stain or culture results suggested infection. Each site participated in both arms after a washout period and crossover. Outcomes were protocol compliance, all-cause 30-day mortality, and ventilator-free alive days at 30 days. Standard statistical techniques were applied. RESULTS: A total of 186 patients had 244 total cultures, of which only the first was analyzed. Ninety-three patients (50%) were enrolled in each arm, and 94.6% were trauma patients (84.4% blunt trauma). The median age was 50.5 years, and 21% of the cohort was female. There were no differences in demographics, comorbidities, sequential organ failure assessment, Acute Physiology and Chronic Health Evaluation II, or Injury Severity Scores. Antibiotics were started significantly later in the specimen-initiated arm (0 vs. 9.3 hours; p < 0.0001) with 19.4% avoiding antibiotics completely for that episode. There were no differences in the rate of protocol adherence, 30-day mortality, or ventilator-free alive days at 30 days. CONCLUSION: In this cluster-randomized crossover trial, we found similar compliance rates between immediate and specimen-initiated antibiotic strategies. Specimen-initiated antibiotic protocol in patients with a suspected hospital-acquired pneumonia did not result in worse clinical outcomes compared with immediate initiation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.