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Original Investigation
Caring for the Critically Ill Patient
June12, 2024
Mohd H.Abdul-Aziz,BPharm, PhD1; Naomi E.Hammond,RN, PhD2,3; Stephen J.Brett,MD4; et al Menino O.Cotta,BPharm, PhD1; Jan J.De Waele,MD, PhD5; AnthonyDevaux,PhD6; Gian LucaDi Tanna,PhD6,7,8; Joel M.Dulhunty,MD, PhD2,9,10,11; HatemElkady,MD12; LarsEriksson,BA13; M. ShahnazHasan,MD14; Ayesha BibiKhan,MD15; JeffreyLipman,MD, DMed1,9,16,17; XiaoqiuLiu,PhD6,18; GiacomoMonti,MD19,20; JohnMyburgh,MD, PhD2,21; EmmanuelNovy,MD22,23; ShahedOmar,MD15; DorrilynRajbhandari,RN2; ClaireRoger,MD, PhD24,25; FredrikSjövall,MD, PhD26,27; IreneZaghi,MD28; AlbertoZangrillo,MD19,20; AnthonyDelaney,MD, PhD2,3; Jason A.Roberts,BPharm, PhD1,9,17,29
Author Affiliations Article Information
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1University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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2Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
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3Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Sydney, New South Wales, Australia
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4Department of Surgery and Cancer, Imperial College, London, United Kingdom
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5Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium
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6Statistics Division, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia
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7Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Manno, Switzerland
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8Department of Clinical Research, University of Bern, Bern, Switzerland
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9Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
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10Redcliffe Hospital, Redcliffe, Queensland, Australia
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11Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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12Department of Intensive Care Medicine, Westmead Hospital, Sydney, New South Wales, Australia
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13UQ Library, The University of Queensland, Brisbane, Queensland, Australia
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14Department of Anesthesiology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
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15Division of Critical Care, University of Witwatersrand, Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa
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16Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
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17Division of Anesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
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18School of Population Health, University of New South Wales, Sydney, New South Wales, Australia
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19Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy
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20Vita-Salute San Raffaele University, Milan, Italy
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21Department of Intensive Care, St George Hospital, Kogarah, New South Wales, Australia
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22Service d’anesthésie-réanimation et médicine péri-opératoire Brabois adulte, CHRU de Nancy, Nancy, France
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23Université de Lorraine, SIMPA, Nancy, France
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24Département d’anesthésie et réanimation, douleur et médecine d’urgence, CHU Carémeau, Nîmes, France
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25UR UM 103IMAGINE, Faculté de Médecine, Montpellier Université, Nîmes, France
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26Intensive and Perioperative Care, Skåne University Hospital, Malmö, Sweden
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27Department of Clinical Sciences, Lund University, Lund, Sweden
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28Department of Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy
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29Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Queensland, Australia
JAMA. Published online June 12, 2024. doi:10.1001/jama.2024.9803
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Continuous vs Intermittent β-Lactam Antibiotic Infusions in Patients With Sepsis
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Question Does the administration of β-lactam antibiotics by prolonged infusion reduce 90-day mortality compared with intermittent infusion in adult patients with sepsis or septic shock?
Findings This systematic review and bayesian meta-analysis of 18 randomized trials that included 9108 critically ill adults with sepsis or septic shock reported a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality compared with intermittent infusions (risk ratio, 0.86).
Meaning Prolonged infusions of β-lactam antibiotics are associated with a reduced risk of death in critically ill adult patients with sepsis or septic shock compared with intermittent infusions.
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
- Editorial Resolving the Dilemma on Continuous vs Intermittent β-Lactam Antibiotics in Sepsis
JAMA
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Infectious Diseases Antibiotic Use, Overuse, Resistance, Stewardship Sepsis Resuscitation Critical Care Medicine
Citation
Abdul-Aziz MH, Hammond NE, Brett SJ, et al. Prolonged vs Intermittent Infusions of β-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis. JAMA. Published online June 12, 2024. doi:10.1001/jama.2024.9803
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