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

Dulhunty, Joel M., Roberts, Jason A., Davis, Joshua S., Webb, Steven A.R., Bellomo, Rinaldo, Gomersall, Charles, Shirwadkar, Charudatt, Eastwood, Glenn M., Myburgh, John, Paterson, David L., Starr, Therese, Paul, Sanjoy K., Lipman, Jeffrey, Bellomo, Rinaldo, Peck, Leah, Young, Helen, Boschert , Catherine, Fletcher, Jason, Smith, Julie, Nand, Kiran, Sara, Treena, Harney, Amy, Rodgers, Helen, Van Haren, Frank, Clarke, Sally, Durham, David, Hannan, Catherine, Matheson, Elisha, Schwartz, Kate, Thomas, Karen, Bone, Allison, Cattigan, Claire, Elderkin, Tania, Salerno, Tania, Cameron, Robert, Ellis, Katrina, Hatter, Sheridan, Davis, Joshua, Sanap, Milind, Soar, Natalie, Wood, Josette, Chan, Karen, Heffernan, Aaron, Lai, Nai An, Moss, Catherine, Sheehy, Kate, Duroux, Maree, Ratcliffe, Megan, Shone, Samantha, Warhurst, Timothy, Dunlop, Rachel, Roberts, Jason, Stuart, Janine, Udy, Andrew, Cooper, David, McAllister, Rick, Cheng, Andrew, Inskip, Deborah, Miller, Jennene, Reynolds, Claire, Rudham, Sam, Baker, Stuart, Hepburn, Kristy, Roberts, Brigit, Woods, Paul, Chatterjee, Indranil, Smith, Judy, Cullen, Martin, Kong, Jing, Nayyar, Vineet, Leung, Patricia, Whitehead, Christina, Gilder, Eileen, McCarthy, Lianne, McGuiness, Shay, Parke, Rachael, Benefield, Kirsten, Chen, Yan, McArthur, Colin, Newby, Lynette, Henderson, Seton, Mehrtens, Jan, Noble, Sascha, Chadwick, Lesley, Freebain, Ross, Hogan, Chantal, Kazemi, Alex, Rust, Laura, Song, Rima, Tilsley, Anna, Williams, Anthony, Andrews, Lynn, Dinsdale, Richard, Hunt, Anna, Hurford, Sally, Mackle, Diane, Ongley, Jessica, Young, Paul, Durning, John, Frengley, Robert, La Pine, Mary, McCracken, Geoff, Sharma, Swarna Baskar, Kollef, Marin, Turnidge, John and Paul, Sanjoy (2015) A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis. American Journal of Respiratory and Critical Care Medicine, 192 11: 1298-1305. doi:10.1164/rccm.201505-0857OC

Author Dulhunty, Joel M.
Roberts, Jason A.
Davis, Joshua S.
Webb, Steven A.R.
Bellomo, Rinaldo
Gomersall, Charles
Shirwadkar, Charudatt
Eastwood, Glenn M.
Myburgh, John
Paterson, David L.
Starr, Therese
Paul, Sanjoy K.
Lipman, Jeffrey
Bellomo, Rinaldo
Peck, Leah
Young, Helen
Boschert , Catherine
Fletcher, Jason
Smith, Julie
Nand, Kiran
Sara, Treena
Harney, Amy
Rodgers, Helen
Van Haren, Frank
Clarke, Sally
Durham, David
Hannan, Catherine
Matheson, Elisha
Schwartz, Kate
Thomas, Karen
Bone, Allison
Cattigan, Claire
Elderkin, Tania
Salerno, Tania
Cameron, Robert
Ellis, Katrina
Hatter, Sheridan
Davis, Joshua
Sanap, Milind
Soar, Natalie
Wood, Josette
Chan, Karen
Heffernan, Aaron
Lai, Nai An
Moss, Catherine
Sheehy, Kate
Duroux, Maree
Ratcliffe, Megan
Shone, Samantha
Warhurst, Timothy
Dunlop, Rachel
Roberts, Jason
Stuart, Janine
Udy, Andrew
Cooper, David
McAllister, Rick
Cheng, Andrew
Inskip, Deborah
Miller, Jennene
Reynolds, Claire
Rudham, Sam
Baker, Stuart
Hepburn, Kristy
Roberts, Brigit
Woods, Paul
Chatterjee, Indranil
Smith, Judy
Cullen, Martin
Kong, Jing
Nayyar, Vineet
Leung, Patricia
Whitehead, Christina
Gilder, Eileen
McCarthy, Lianne
McGuiness, Shay
Parke, Rachael
Benefield, Kirsten
Chen, Yan
McArthur, Colin
Newby, Lynette
Henderson, Seton
Mehrtens, Jan
Noble, Sascha
Chadwick, Lesley
Freebain, Ross
Hogan, Chantal
Kazemi, Alex
Rust, Laura
Song, Rima
Tilsley, Anna
Williams, Anthony
Andrews, Lynn
Dinsdale, Richard
Hunt, Anna
Hurford, Sally
Mackle, Diane
Ongley, Jessica
Young, Paul
Durning, John
Frengley, Robert
La Pine, Mary
McCracken, Geoff
Sharma, Swarna Baskar
Kollef, Marin
Turnidge, John
Paul, Sanjoy
Title A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis
Journal name American Journal of Respiratory and Critical Care Medicine   Check publisher's open access policy
ISSN 1535-4970
Publication date 2015-12-01
Year available 2015
Sub-type Article (original research)
DOI 10.1164/rccm.201505-0857OC
Open Access Status Not yet assessed
Volume 192
Issue 11
Start page 1298
End page 1305
Total pages 8
Place of publication New York, United States
Publisher American Thoracic Society
Language eng
Subject 2740 Pulmonary and Respiratory Medicine
2706 Critical Care and Intensive Care Medicine
Abstract Rationale: Continuous infusion of beta-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing.
Formatted abstract
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.
Keyword Antibiotic
Clinical outcome
Intensive care
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
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