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Type: Journal article
Title: A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis
Other Titles: A multicenter randomized trial of continuous versus intermittent beta-lactam infusion in severe sepsis
Author: Dulhunty, J.
Roberts, J.
Davis, J.
Webb, S.
Bellomo, R.
Gomersall, C.
Shirwadkar, C.
Eastwood, G.
Myburgh, J.
Paterson, D.
Starr, T.
Paul, S.
Lipman, J.
Peck, L.
Young, H.
Boschert, C.
Fletcher, J.
Smith, J.
Nand, K.
Sara, T.
et al.
Citation: American Journal of Respiratory and Critical Care Medicine, 2015; 192(11):1298-1305
Publisher: ATS Journals
Issue Date: 2015
ISSN: 1073-449X
Statement of
Joel M. Dulhunty, Jason A. Roberts, Joshua S. Davis, Steven A. R. Webb, Rinaldo Bellomo ... Milind Sanap ... et al.
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.
Keywords: BLING II Investigators for the ANZICS Clinical Trials Group *
Anti-Bacterial Agents
Treatment Outcome
Length of Stay
Infusions, Intravenous
Drug Administration Schedule
Survival Analysis
Prospective Studies
Double-Blind Method
Middle Aged
Rights: © 2015 by the American Thoracic Society
DOI: 10.1164/rccm.201505-0857OC
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