{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:12:09Z","timestamp":1793319129399,"version":"4.5.0"},"reference-count":48,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2024,8,27]]},"abstract":"\n Importance<\/jats:title>\n There is uncertainty about whether prolonged infusions of \u03b2-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To determine whether prolonged \u03b2-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of \u03b2-lactam antibiotics in critically ill adults with sepsis or septic shock.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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 \u03b2-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200921.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of \u03b2-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).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged \u03b2-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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n PROSPERO Identifier:\n CRD42023399434<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2024.9803","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T04:30:48Z","timestamp":1718166648000},"page":"638","source":"Crossref","is-referenced-by-count":184,"title":["Prolonged vs Intermittent Infusions of \u03b2-Lactam Antibiotics in Adults With Sepsis or Septic Shock"],"prefix":"10.1001","volume":"332","author":[{"given":"Mohd H.","family":"Abdul-Aziz","sequence":"first","affiliation":[{"name":"University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi E.","family":"Hammond","sequence":"additional","affiliation":[{"name":"Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Malcolm Fisher Department of Intensive Care, Royal North Shore Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Brett","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menino O.","family":"Cotta","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan J.","family":"De Waele","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Devaux","sequence":"additional","affiliation":[{"name":"Statistics Division, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Luca","family":"Di Tanna","sequence":"additional","affiliation":[{"name":"Statistics Division, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Manno, Switzerland"},{"name":"Department of Clinical Research, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel M.","family":"Dulhunty","sequence":"additional","affiliation":[{"name":"Critical Care Program, The George Institute for Global Health and University of New South Wales, Sydney, New South Wales, Australia"},{"name":"Department of Intensive Care Medicine, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia"},{"name":"Redcliffe Hospital, Redcliffe, Queensland, Australia"},{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem","family":"Elkady","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Westmead Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eriksson","sequence":"additional","affiliation":[{"name":"UQ Library, The University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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