- Title
- A multicenter randomized trial of continuous versus intermittent β-lactam infusion in severe sepsis
- Creator
- Dulhunty, Joel M.; Roberts, Jason A.; Starr, Therese; Paul, Sanjoy K.; Lipman, Jeffrey; Davis, Joshua S.; Webb, Steven A. R.; Bellomo, Rinaldo; Gomersall, Charles; Shirwadkar, Charudatt; Eastwood, Glenn M.; Myburgh, John; Paterson, David L.
- Relation
- American Journal of Respiratory and Critical Care Medicine Vol. 192, Issue 11, p. 1298-1305
- Publisher Link
- http://dx.doi.org/10.1164/rccm.201505-0857OC
- Publisher
- American Thoracic Society
- Resource Type
- journal article
- Date
- 2015
- Description
- Continuous infusion of β-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing. To evaluate the efficacy of continuous versus intermittent infusion in patients with severe sepsis. 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. 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). In critically ill patients with severe sepsis, there was no difference in outcomes between β-lactam antibiotic administration by continuous and intermittent infusion.
- Subject
- antibiotic; clinical outcome; intensive care; pharmacodynamics; pharmacokinetics
- Identifier
- http://hdl.handle.net/1959.13/1321738
- Identifier
- uon:24441
- Identifier
- ISSN:1073-449X
- Language
- eng
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