Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on intensive care unit patient prognosis: a causal inference approach using data from the Eurobact2 study.
Journal
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN
1469-0691
Date Issued
2024-09-24
Author(s)
Loiodice, Ambre
Bailly, Sébastien
Ruckly, Stéphane
Buetti, Niccolò
Barbier, François
Staiquly, Quentin
Tabah, Alexis
Timsit, Jean-François
EUROBACT-2 Study Group, the European Society of Intensive Care Medicine (ESICM), the European Society of Clinical Microbiology, the Infectious Diseases (ESCMID) Study Group for Infections in Critically Ill Patients (ESGCIP) and the OUTCOMEREA Network
et al.
Abstract
Objectives: Hospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU) are common life-threatening events. We aimed to investigate the association between early adequate antibiotic therapy and 28-day mortality in ICU patients who survived at least 1 day after the onset of HA-BSI.
Methods: We used individual data from a prospective, observational, multicentre, and intercontinental cohort study (Eurobact2). We included patients who were followed for ≥1 day and for whom time-to-appropriate treatment was available. We used an adjusted frailty Cox proportional-hazard model to assess the effect of time-to-treatment-adequacy on 28-day mortality. Infection- and patient-related variables identified as confounders by the Directed Acyclic Graph were used for adjustment. Adequate therapy within 24 hours was used for the primary analysis. Secondary analyses were performed for adequate therapy within 48 and 72 hours and for identified patient subgroups.
Results: Among the 2418 patients included in 330 centres worldwide, 28-day mortality was 32.8% (n = 402/1226) in patients who were adequately treated within 24 hours after HA-BSI onset and 40% (n = 477/1192) in inadequately treated patients (p < 0.01). Adequacy within 24 hours was more common in young, immunosuppressed patients, and with HA-BSI due to Gram-negative pathogens. Antimicrobial adequacy was significantly associated with 28-day survival (adjusted Hazard Ratio (aHR), 0.83; 95% CI, 0.72-0.96; p 0.01). The estimated population attributable fraction of 28-day mortality of inadequate therapy was 9.15% (95% CI, 1.9-16.2%).
Discussion: In patients with HA-BSI admitted to the ICU, the population attributable fraction of 28-day mortality of inadequate therapy within 24 hours was 9.15%. This estimate should be used when hypothesizing the possible benefit of any intervention aiming at reducing the time-to-appropriate antimicrobial therapy in HA-BSI.
Subjects
Adequacy
Critically ill
Directed acyclic Graph
Hospital-acquired bloodstream infection
Mediation analysis
Sepsis
Time-to-antibiotic
Publisher
Elsevier B.V.
Type
journal article