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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. and Lipman, Jeffrey (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.

Document type: Journal Article
Citation counts: Altmetric Score Altmetric Score is 73
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IRMA ID 10444xPUB30
Title A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis
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
Journal Name American Journal of Respiratory and Critical Care Medicine
Publication Date 2015
Volume Number 192
Issue Number 11
ISSN 1073-449X   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84946231220
Start Page 1298
End Page 1305
Total Pages 8
Place of Publication United States of America
Publisher American Thoracic Society
HERDC Category C1 - Journal Article (DIISR)
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 Antibiotic
Clinical outcome
Intensive care
Pharacodynamics
Pharmacokinetics
DOI http://dx.doi.org/10.1164/rccm.201505-0857OC   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
 
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