Association between augmented renal clearance and clinical outcomes in patients receiving β-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised, placebo-controlled, clinical trial

Andrew Udy, 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, Rinaldo Bellomo, Glenn Eastwood, Leah Peck, Helen Young, Catherine Boschert, Jason FletcherJulie Smith, Kiran Nand, Treena Sara, Charudatt Shirwadkar, Amy 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, Joshua S. Davis, 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, Joel Dulhunty, Rachel Dunlop, Jeffrey Lipman, David Paterson, Jason Roberts, Therese Starr, Janine Stuart, Andrew Udy, David Cooper, Rick McAllister, Steve Webb, Andrew Cheng, Deborah Inskip, Jennene Miller, John Myburgh, Serena Knowles, Claire Reynolds, Sam Rudham, Stuart Baker, Kristy Hepburn, Brigit Roberts, Paul Woods, Indranil Chatterjee, Judy Smith, Martin Cullen, Jing Kong, Vineet Nayyar, Christina Whitehead, Charles Gomersall, 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, John Durning, Robert Frengley, Mary La Pine, Geoff McCracken, Swarna Baskar Sharma, Lynn Andrews, Richard Dinsdale, Anna Hunt, Sally Hurford, Diane Mackle, Jessica Ongley, Paul Young, Jeffrey Lipman, Rinaldo Bellomo, Joshua S. Davis, Joel Dulhunty, Glenn Eastwood, Charles Gomersall, John Myburgh, David Paterson, Jason Roberts, Charudatt Shirwadkar, Therese Starr, Steve Webb, Marin Kollef, John Turnidge, Sanjoy Paul

    Research output: Contribution to journalArticle

    Abstract

    Augmented renal clearance (ARC) is known to influence β-lactam antibiotic pharmacokinetics. This substudy of the BLING-II trial aimed to explore the association between ARC and patient outcomes in a large randomised clinical trial. BLING-II enrolled 432 participants with severe sepsis randomised to receive β-lactam therapy by continuous or intermittent infusion. An 8-h creatinine clearance (CLCr) measured on Day 1 was used to identify ARC, defined as CLCr ≥ 130 mL/min. Patients receiving any form of renal replacement therapy were excluded. Primary outcome was alive ICU-free days at Day 28. Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation. A total of 254 patients were included, among which 45 (17.7%) manifested ARC [median (IQR) CLCr 165 (144–198) mL/min]. ARC patients were younger (P < 0.001), more commonly male (P = 0.04) and had less organ dysfunction (P < 0.001). There was no difference in ICU-free days at Day 28 [ARC, 21 (12–24) days; no ARC, 21 (11–25) days; P = 0.89], although clinical cure was significantly greater in the unadjusted analysis in those manifesting ARC [33/45 (73.3%) vs. 115/209 (55.0%) P = 0.02]. This was attenuated in the multivariable analysis. No difference was noted in 90-day mortality. There were no statistically significant differences in clinical outcomes in ARC patients according to the dosing strategy employed. In this substudy of a large clinical trial of β-lactam antibiotics in severe sepsis, ARC was not associated with any differences in outcomes, regardless of dosing strategy.

    Original languageEnglish
    Pages (from-to)624-630
    Number of pages7
    JournalInternational Journal of Antimicrobial Agents
    Volume49
    Issue number5
    DOIs
    Publication statusPublished - May 2017

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