Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis

Abdul-Aziz MH 1 , Hammond NE 2 , Brett SJ 3 , Cotta MO 1 , De Waele JJ 4 , Devaux A 5 Show all authors , Di Tanna GL 5 , Dulhunty JM 2 , Elkady H 6 , Eriksson L 7 , Hasan MS 8 , Khan AB 9 , Lipman J 1 , Liu X 5 , Monti G 10 , Myburgh J 2 , Novy E 11 , Omar S 9 , Rajbhandari D 2 , Roger C 12 , Sjövall F 13 , Zaghi I 14 , Zangrillo A 10 , Delaney A 2 , Roberts JA 1

Affiliations 

  • 1 University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
  • 2 Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
  • 3 Department of Surgery and Cancer, Imperial College, London, United Kingdom
  • 4 Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium
  • 5 Statistics Division, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
  • 6 Department of Intensive Care Medicine, Westmead Hospital, Sydney, New South Wales, Australia
  • 7 UQ Library, The University of Queensland, Brisbane, Queensland, Australia
  • 8 Department of Anesthesiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
  • 9 Division of Critical Care, University of Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
  • 10 Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
  • 11 Service d'anesthésie-réanimation et médicine péri-opératoire Brabois adulte, CHRU de Nancy, Nancy, France
  • 12 Département d'anesthésie et réanimation, douleur et médecine d'urgence, CHU Carémeau, Nîmes, France
  • 13 Intensive and Perioperative Care, Skåne University Hospital, Malmö, Sweden
  • 14 Department of Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy
JAMA, 2024 Aug 27;332(8):638-648.
PMID: 38864162 DOI: 10.1001/jama.2024.9803

Abstract

IMPORTANCE: There is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock.

OBJECTIVE: To determine whether prolonged β-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions.

DATA SOURCES: The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024.

STUDY SELECTION: Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of β-lactam antibiotics in critically ill adults with sepsis or septic shock.

DATA EXTRACTION AND SYNTHESIS: Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach.

MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure.

RESULTS: From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of β-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of β-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty).

CONCLUSIONS AND RELEVANCE: Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged β-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock.

TRIAL REGISTRATION: PROSPERO Identifier: CRD42023399434.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications