Clinical Outcomes of Early Phenotype-Desirable Antimicrobial Therapy for Enterobacterales Bacteremia
Open accessAbstract
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.
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Improvements in TAT and faster treatment adaptation have been attributed to better outcomes in patients with BSI, including improved survival rates in some studies.
“While the exact cause of this finding cannot be determined due to the observational nature of the study, improvements in TAT and faster treatment adaptation have been attributed to better outcomes in patients with BSI, including improved survival rates in some studies [23–25].”
From Lab efficiency and improvements in the management of bloodstream infections: a before and after study (2025) · cites this paper as [25]
The Introduction (page unavailable) links delayed identification and susceptibility results to delayed treatment optimization and poorer bloodstream-infection outcomes, including increased mortality risk with discordant therapy. The Discussion (page unavailable) reports better overall outcomes with earlier targeted treatment, but explicitly says this study found no mortality difference. It therefore supports the general link, not a survival benefit from improved turnaround time in this study. (LLM, conf=0.86)
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Research works printed but not linked: 26
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Cited by
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Paluch, M., Ettahar, N., Lagraulet, B., Cattoen, C., Rethore, E., Dubrulle, A., Abad, L., Canis, F., Wayenberg, L., Lambiotte, F., et al. (2025) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-025-05200-x · Cited by 5 · see citing works
- Authors
- Moon, R. C., MacVane, S. H., David, J., Morton, J. B., Rosenthal, N., & Claeys, K. C.
- Affiliations
- PINC AI Applied Sciences, Premier Inc, Charlotte, North Carolina
- Global Medical Affairs, bioMérieux, Salt Lake City, Utah
- Global Marketing, bioMérieux, Salt Lake City, Utah
- University of Maryland, Baltimore (US)
- Corresponding author
- Moon, Rena C.
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2024-12-23
- Volume
- 7
- Issue
- 12
- Pages
- e2451633
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC11667351
- OpenAlex
- W4405721256
- Cited by
- 8
- References
- 0
- Citations by year
- 2026: 5 · 2025: 3
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- JAMA Network Open (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- gram-negative bacteremia, beta-lactam antibiotics, antimicrobial stewardship, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, Proteus mirabilis, 30-day mortality, length of hospital stay
- MeSH terms
- Antimicrobial Stewardship, Adult, Aged, Anti-Bacterial Agents, Enterobacteriaceae Infections, Female, Humans, Male, Middle Aged, Phenotype, Retrospective Studies, Bacteremia, Treatment Outcome
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