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 A. Udy, Joel M. Dulhunty, Jason A. Roberts, Joshua S. 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 & 83 others Treena Sara, 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, 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, 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, Judy Smith, 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, 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, Marin Kollef, John Turnidge

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27 Citations (Scopus)

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.

LanguageEnglish
Pages624-630
Number of pages7
JournalInternational Journal of Antimicrobial Agents
Volume49
Issue number5
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • Augmented renal clearance
  • Critical illness
  • Sepsis
  • β-Lactams

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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