Importance: Initiating effective therapy early is associated with improved survival among patients hospitalized with gram-negative bloodstream infections; furthermore, providing early phenotype-desirable antimicrobial therapy (PDAT; defined as receipt of a β-lactam antibiotic with the narrowest spectrum of activity to effectively treat the pathogen's phenotype) is crucial for antimicrobial stewardship. However, the timing of targeted therapy among patients hospitalized with gram-negative bloodstream infections is not well understood.
Objective: To compare the clinical outcomes between patients who were hospitalized with Enterobacterales bloodstream infections receiving early vs delayed PDAT.
Design, setting, and participants: This retrospective cohort study used a large, geographically diverse, hospital-based US database (PINC AI Healthcare Database). Participants were adult (aged ≥18 years) patients with an inpatient admission between January 1, 2017, and June 30, 2022, with at least 1 blood culture isolate positive for Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, or Proteus mirabilis and receiving PDAT on blood culture collection days 0 to 4.
Exposure: Early vs delayed PDAT, with early PDAT defined as receipt of PDAT on blood culture collection days 0 to 2.
Main outcomes and measures: The main outcome was desirability of outcome ranking, in which patients were assigned a mutually exclusive rank 1 through 5. Rank 1 indicated the most desirable outcome (alive with no events), whereas rank 5 indicated the least desirable outcome and included all patients who died within 30 days of blood culture collection.
Results: Among 8193 eligible patients (mean [SD] age, 69.0 [16.4] years; 4758 [58.1%] female; 1200 [14.6%] African American or Black, 729 [8.9%] Hispanic, and 5778 [70.5%] White) from 252 hospitals, 5033 (61.4%) received early PDAT. Patients receiving early PDAT were similar in age (mean [SD], 68.2 [16.9] vs 70.3 [15.6] years) but more likely to have a lower median (IQR) Charlson-Deyo comorbidity score (2 [1-5] vs 3 [1-5]) compared with patients receiving delayed PDAT. After adjusting for comorbidities and severity of illness, patients receiving early PDAT were 20% less likely to be readmitted within 30 days compared with those receiving delayed PDAT (odds ratio, 0.80; 95% CI, 0.69-0.92; P < .001). A higher percentage of patients receiving early PDAT had a desirability of outcome ranking of 1 compared with patients receiving delayed PDAT (56.3% vs 52.2%, P < .001). Those receiving early PDAT had a 52.5% probability (95% CI, 51.3%-53.7%) of a more desirable outcome than those receiving delayed PDAT, a finding that persisted in the adjusted analysis (probability, 52.0%; 95% CI, 50.9%-53.2%).
Conclusions and relevance: Receiving early PDAT was associated with favorable 30-day clinical outcomes among patients hospitalized with Enterobacterales blood stream infections. Early PDAT may be important not only for antimicrobial stewardship but also for improving patient outcomes.