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Multicenter Study
. 2025 May 1;53(5):e1066-e1079.
doi: 10.1097/CCM.0000000000006606. Epub 2025 Feb 26.

Prognostic Impact of Early Appropriate Antimicrobial Therapy in Critically Ill Patients With Nosocomial Pneumonia Due to Gram-Negative Pathogens: A Multicenter Cohort Study

François Barbier  1 , Niccolò Buetti  2   3 , Claire Dupuis  4 , Carole Schwebel  5 , Élie Azoulay  6 , Laurent Argaud  7 , Yves Cohen  8 , Vivien Hong Tuan Ha  9 , Marc Gainnier  10 , Shidasp Siami  11 , Jean-Marie Forel  12 , Christophe Adrie  13 , Étienne de Montmollin  14 , Jean Reignier  15 , Stéphane Ruckly  16 , Jean-Ralph Zahar  3   17 , Jean-François Timsit  3   14 ; OutcomeRéa Study Group
Collaborators, Affiliations
Multicenter Study

Prognostic Impact of Early Appropriate Antimicrobial Therapy in Critically Ill Patients With Nosocomial Pneumonia Due to Gram-Negative Pathogens: A Multicenter Cohort Study

François Barbier et al. Crit Care Med. .

Abstract

Objectives: To evaluate whether early appropriate antimicrobial therapy (EAAT) is associated with improved outcomes in critically ill patients with hospital-acquired pneumonia (HAP), ventilated HAP (vHAP), or ventilator-associated pneumonia (VAP) involving Gram-negative bacteria (GNB).

Design: Retrospective cohort study based on prospectively collected data.

Setting: Thirty-two French ICUs (OutcomeRéa network).

Patients: All patients with a first HAP, vHAP, or VAP due to GNB during their ICU stay.

Interventions: None.

Measurements and main results: The relationship between EAAT and day 28 all-cause mortality (primary endpoint) was explored through Cox proportional-hazard models, with subgroup analyses according to pneumonia types, causative GNB, features of EAAT, and the occurrence of septic shock at pneumonia diagnosis. The course of Sequential Organ Failure Assessment (SOFA) score values, the clinical cure rate at day 14, and the time to mechanical ventilation (MV) weaning and ICU discharge after pneumonia diagnosis were investigated as secondary endpoints. Among the 804 included patients, 495 (61.6%) received EAAT (single-drug, 25.4%; combination, 36.2%). Day 28 mortality was 32.6%. EAAT was not independently associated with this outcome (adjusted hazard ratio, 0.87; 95% CI, 0.67-1.12). This result was confirmed in subgroup analyses as in a second model considering all episodes of pneumonia occurring during the ICU stay. EAAT was not associated with a faster decrease in SOFA score values ( p = 0.11), a higher day 14 clinical cure rate (overall, 43.7%), or a shorter MV duration (cause-specific hazard ratio [HR] for extubation, 0.84; 95% CI, 0.69-1.01) or ICU stay (cause-specific HR for discharge alive, 0.85; 95% CI, 0.72-1.00).

Conclusions: In this study, EAAT was not associated with a reduced day 28 mortality, a faster resolution of organ failure, a higher day 14 clinical cure rate, or a shorter time to MV weaning or ICU discharge in critically ill patients with HAP, vHAP, or VAP due to GNB. However, a prognostic benefit from EAAT cannot be ruled out due to lack of statistical power.

Keywords: Enterobacterales; antimicrobial therapy; hospital-acquired pneumonia; outcome; ventilated hospital-acquired pneumonia; ventilator-associated pneumonia.

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Conflict of interest statement

Dr. Barbier received lecture fees and funding from MSD, lecture fees from BioMérieux, consulting fees from Shionogi, conference invitation from Pfizer, and lecture fees from Advanz Pharma. Dr. Timsit received consulting fees from Gilead, MSD, Pfizer, BioMérieux, and Roche Diagnostics and lecture fees from MSD, Pfizer, Shionogi, BioMérieux, Qiagen, Mundipharma, and Gilead not related to the submitted work. Dr. Zahar received consulting fees and conference invitations from MSD; consulting fees, lecture fees, and conference invitations from Pfizer; lecture fees from Advanz Pharma and Shionogi; and conference invitations from BioMérieux and Gilead not related to the submitted work. Dr. Buetti’s institution received funding from the Swiss National Science Foundation. Dr. Azoulay’s institution received funding from Pfizer, Mundipharma, and General Electric; he received funding from Sanofi, Alexion, and Gilead. The remaining authors have disclosed that they do not have any potential conflicts of interest.

References

    1. European Centre for Disease Prevention and Control: Point Prevalence Survey of Healthcare-Associated Infections and Antimicrobial Use in European Acute Care Hospitals. 2013. Available at: https://ecdc.europa.eu/sites/portal/files/media/en/publications/Publicat... . Accessed May 1, 2024
    1. Magill SS, O’Leary E, Janelle SJ, et al.; Emerging Infections Program Hospital Prevalence Survey Team: Changes in prevalence of healthcare-associated infections in U.S. hospitals. N Engl J Med. 2018; 379:1732–1744
    1. Melsen WG, Rovers MM, Groenwold RHH, et al.: Attributable mortality of ventilator-associated pneumonia: A meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis. 2013; 13:665–671
    1. Micek ST, Chew B, Hampton N, et al.: A case-control study assessing the impact of nonventilated hospital-acquired pneumonia on patient outcomes. Chest. 2016; 150:1008–1014
    1. Ibn Saied W, Mourvillier B, Cohen Y, et al.; OUTCOMEREA Study Group: A comparison of the mortality risk associated with ventilator-acquired bacterial pneumonia and nonventilator ICU-acquired bacterial pneumonia. Crit Care Med. 2019; 47:345–352

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