A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis

Joel M. Dulhunty, Jason A. Roberts, Joshua Davis, Steven A R Webb, Rinaldo Bellomo, Charles Gomersall, Charudatt Shirwadkar, Glenn M. Eastwood, John Myburgh, David L. Paterson, Therese Starr, Sanjoy K. Paul, Jeffrey Lipman, Leah Peck, Helen Young, Catherine Boschert, Jason Fletcher, Julie Smith, Kiran Nand, Treena SaraAmy Harney, Helen Rodgers, Frank Van Haren, Sally Clarke, David Durham, Catherine Hannan, Elisha Matheson, Kate Schwartz, Karen Thomas, Allison Bone, Claire Cattigan, Tania Elderkin, Tania Salerno, Robert Cameron, Katrina Ellis, Sheridan Hatter, Milind Sanap, Natalie Soar, Josette Wood, Karen Chan, Aaron Heffernan, Nai An Lai, Catherine Moss, Kate Sheehy, Maree Duroux, Megan Ratcliffe, Samantha Shone, Timothy Warhurst, Rachel Dunlop, Janine Stuart, Andrew Udy, David Cooper, Rick McAllister, Andrew Cheng, Deborah Inskip, Jennene Miller, Serena Knowles, Claire Reynolds, Sam Rudham, Stuart Baker, Kristy Hepburn, Brigit Roberts, Paul Woods, Indranil Chatterjee, Martin Cullen, Jing Kong, Vineet Nayyar, Christina Whitehead, Patricia Leung, Eileen Gilder, Lianne McCarthy, Shay McGuiness, Rachael Parke, Kirsten Benefield, Yan Chen, Colin McArthur, Lynette Newby, Seton Henderson, Jan Mehrtens, Sascha Noble, Lesley Chadwick, Ross Freebain, Chantal Hogan, Alex Kazemi, Laura Rust, Rima Song, Anna Tilsley, Anthony Williams, Lynn Andrews, Richard Dinsdale, Anna Hunt, Sally Hurford, Diane Mackle, Jessica Ongley, Paul Young, John Durning, Robert Frengley, Mary La Pine, Geoff McCracken, Swarna Baskar Sharma, Marin Kollef, John Turnidge, Sanjoy Paul, BLING II Investigators for the ANZICS Clinical Trials Group

    Research output: Contribution to journalArticlepeer-review


    Rationale: Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing.

    Objectives:  To evaluate the efficacy of continuous versus intermittent infusion in patients with severe sepsis.

    Methods: We conducted a randomized controlled trial in 25 intensive care units (ICUs). Participants commenced on piperacillin–tazobactam, ticarcillin–clavulanate, or meropenem were randomized to receive the prescribed antibiotic via continuous or 30-minute intermittent infusion for the remainder of the treatment course or until ICU discharge. The primary outcome was the number of alive ICU-free days at Day 28. Secondary outcomes were 90-day survival, clinical cure 14 days post antibiotic cessation, alive organ failure–free days at Day 14, and duration of bacteremia.

    Measurements and Main Results:  We enrolled 432 eligible participants with a median age of 64 years and an Acute Physiology and Chronic Health Evaluation II score of 20. There was no difference in ICU-free days: 18 days (interquartile range, 2–24) and 20 days (interquartile range, 3–24) in the continuous and intermittent groups (P = 0.38). There was no difference in 90-day survival: 74.3% (156 of 210) and 72.5% (158 of 218); hazard ratio, 0.91 (95% confidence interval, 0.63–1.31; P = 0.61). Clinical cure was 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12 (95% confidence interval, 0.77–1.63; P = 0.56). There was no difference in organ failure–free days (6 d; P = 0.27) and duration of bacteremia (0 d; P = 0.24).

    Conclusions: In critically ill patients with severe sepsis, there was no difference in outcomes between β-lactam antibiotic administration by continuous and intermittent infusion.

    Original languageEnglish
    Pages (from-to)1298-1305
    Number of pages8
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Issue number11
    Publication statusPublished - 1 Dec 2015


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