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Publications

Journal Article Ahead of print

PubMed: 42228012 DOI: 10.1007/s00134-026-08448-9

Impact of appropriate antimicrobial therapy on patient outcomes and antimicrobial use: a sub analysis of the DIANA Study Dataset.

Intensive Care Med

Authors: José Pedro Cidade, Pedro Póvoa, Pieter Depuydt, Sofie Dhaese, Ken De Smet, Alexis Tabah, Murat Akova, Menino Osbert Cotta, Gennaro De Pascale, George Dimopoulos, Shigeki Fujitani, Jose Garnacho-Montero, Marc Leone, Jeffrey Lipman, Marlies Ostermann, José-Artur Paiva, Jeroen Schouten, Fredrik Sjövall, Jean-François Timsit, Jason A Roberts, Jean Ralph Zahar, Farid Zand, Kapil Zirpe, Jan J De Waele, Liesbet De Bus

Affiliations

  • Intensive Care Unit 4, Department of Intensive Care, São Francisco Xavier Hospital, ULSLO, Lisbon, Portugal.
  • Nova Medical School, Clinical Medicine, CHRC, NOVA University of Lisbon, Lisbon, Portugal.
  • Center for Clinical Epidemiology and Research Unit of Clinical Epidemiology, OUH Odense University Hospital, 5000, Odense C, Denmark.
  • Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium.
  • Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
  • Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
  • Division of Nephrology and Infectious Diseases, AZ Sint-Jan Brugge, Bruges, Belgium.
  • Department of Emergency Medicine, Leuven University Hospitals, Leuven, Belgium.
  • Intensive Care Unit, Redcliffe Hospital, Redcliffe, QLD, Australia.
  • Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
  • Faculty of Health, Queensland University of Technology, Brisbane, Australia.
  • Department of Infectious Diseases and Clinical Microbiology, Hacettepe University School of Medicine, Ankara, Turkey.
  • University of Queensland Centre of Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
  • Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia.
  • Centre of Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
  • Dipartimento di Scienza dell'Emergenza, Anestesiologiche e della Rianimazione - UOC di Anestesia, Rianimazione, Terapia Intensiva e Tossicologia Clinica - Istituto di Anestesia e Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
  • Università Cattolica del Sacro Cuore, Rome, Italy.
  • Department of Critical Care, EVGENIDIO Hospital, Athens, Greece.
  • Medical School, University of Athens, Athens, Greece.
  • Emergency Medicine and Critical Care Medicine, St. Marianna University Hospital, Kawasaki, Kanagawa, Japan.
  • Intensive Care Clinical Unit, Hospital Universitario Virgen del Rocío, Seville, Spain.
  • Aix-Marseille Universite, Assistance Publique Hopitaux de Marseille, Hopital Nord, Service d'Anesthesie et de Reanimation, Marseille, France.
  • UR-UM 103, University of Montpellier, Division of Anesthesia, Critical Care, Emergency and Pain Medicine, Nîmes University Hospital, Nîmes, France.
  • Jamieson Trauma Institute, Royal Brisbane and Women's Hospital, and Queensland University of Technology, Brisbane, Australia.
  • Department of Critical Care, King's College London, Guy's and St Thomas' Hospital, London, UK.
  • Intensive Care Department, Unidade Local de Saude Sao Joao EPE, Porto, Portugal.
  • Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
  • Grupo de Infeccao e Sepsis, Porto, Portugal.
  • Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Scientific Center for Quality of Healthcare, IQ Healthcare, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Department of Intensive and Perioperative Care, Skane University Hospital, Malmo, Sweden.
  • Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Universite de Paris, Sorbonne Paris Cite, UMR 1137, IAME, Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat-Claude Bernard Hospital, 75018, Paris, France.
  • Frazer Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Australia.
  • Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia.
  • Department of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
  • Prevention du Risque Infectieux et Maitrise de l'Antibiothérapie Unit, GH Paris Seine Saint Denis, APHP, Bobigny, France.
  • Shiraz Anesthesiology and Critical Care Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • Grant Medical Foundation, Ruby Hall Clinic, Pune, Maharashtra, India.
  • Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium.
  • Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

Abstract

OBJECTIVE

Although inappropriate therapy has been consistently associated with adverse outcomes, the magnitude and consistency of the benefit associated with appropriate empiric therapy in critically ill patients remain uncertain. We aimed to quantify the prevalence of appropriate empiric antimicrobial therapy and evaluate its association with outcomes and antimicrobial exposure in a large international ICU cohort.

METHODS

This predefined sub-analysis of the DIANA study included adult ICU patients receiving empirical antimicrobials for suspected or confirmed bacterial infection. Only patients with microbiologically confirmed infections were analyzed, and therapy was classified as appropriate if at least one agent demonstrated in vitro activity against the identified pathogen. Associations with 28-day mortality and antimicrobial-free days were assessed using multivariable logistic and Cox regression models. Pre-specified interaction analyses explored effect modification by disease severity and diagnostic certainty.

RESULTS

Of 845 patients with microbiologically confirmed infections, 87.7% received appropriate empirical antimicrobial therapy. Compared with inappropriate therapy, appropriate therapy was associated with significantly lower ICU mortality and longer 28-day antimicrobial-free days and mechanical ventilation-free days. After multivariable adjustment, appropriate therapy remained independently associated with reduced 28-day mortality [adjusted odds ratio (OR) 1.83, 95% confidence interval 1.11-3.06, p = 0.02; hazard ratio (HR) 1.51, 95% CI 1.03-2.21, p = 0.035]. Effect-modification analyses demonstrated that the survival benefit of appropriate therapy was consistent across levels of diagnostic certainty and was most pronounced in patients with moderate illness severity (SOFA 3-9).

CONCLUSION

In critically ill ICU patients, appropriate empirical antimicrobial therapy is independently associated with reduced 28-day mortality rates.

MeSH

Mortality, Critical Care, Critical Illness, Therapeutics, Intensive Care Units, Infections