TY - JOUR
T1 - Effect of adequacy of empirical antibiotic therapy for hospital-acquired bloodstream infections on intensive care unit patient prognosis
T2 - a causal inference approach using data from the Eurobact2 study
AU - 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
AU - Loiodice, Ambre
AU - Bailly, Sébastien
AU - Ruckly, Stéphane
AU - Buetti, Niccolò
AU - Barbier, François
AU - Staiquly, Quentin
AU - Tabah, Alexis
AU - Timsit, Jean François
AU - Lipman, Jeffrey
AU - Pollock, Hamish
AU - Ben Margetts, Margetts
AU - Udy, Andrew
AU - Young, Meredith
AU - Bhadange, Neeraj
AU - Tyler, Steven
AU - Ledtischke, Anne
AU - Finnis, Mackenzie
AU - Dwivedi, Jyotsna
AU - Saxena, Manoj
AU - Biradar, Vishwanath
AU - Soar, Natalie
AU - Sarode, Vineet
AU - Brewster, David
AU - Regli, Adrian
AU - Weeda, Elizabeth
AU - Ahmed, Samiul
AU - Fourie, Cheryl
AU - Laupland, Kevin
AU - Ramanan, Mahesh
AU - Walsham, James
AU - Meyer, Jason
AU - Litton, Edward
AU - Maria Palermo, Anna
AU - Yap, Timothy
AU - Eroglu, Ege
AU - George Attokaran, Antony
AU - Jaramillo, C'havala
AU - Nafees, Khalid Mk
AU - Nafees, Khalid Mahmood Khan
AU - Aqilah Haji Abd Rashid, Nurhikmahtul
AU - Adi Muhamad Ibnu Walid, Haji
AU - Mon, Tomas
AU - Dhakshina Moorthi, P.
AU - Sudhirchandra, Shah
AU - Sridharan, Dhadappa Damodar
AU - Haibo, Qiu
AU - Xie, Jianfeng
AU - Jianfeng, Xie
AU - Wei-Hua, Lu
AU - Lance, Marcus
N1 - Publisher Copyright:
© 2024 European Society of Clinical Microbiology and Infectious Diseases
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Adequacy
KW - Critically ill
KW - Directed acyclic Graph
KW - Hospital-acquired bloodstream infection
KW - Mediation analysis
KW - Sepsis
KW - Time-to-antibiotic
UR - http://www.scopus.com/inward/record.url?scp=85206947039&partnerID=8YFLogxK
U2 - 10.1016/j.cmi.2024.09.011
DO - 10.1016/j.cmi.2024.09.011
M3 - Article
C2 - 39326671
AN - SCOPUS:85206947039
SN - 1198-743X
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
ER -