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.2018-07-022018-07-022015American Journal of Respiratory and Critical Care Medicine, 2015; 192(11):1298-13051073-449X1535-4970http://hdl.handle.net/2440/113165Rationale: 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.en© 2015 by the American Thoracic SocietyBLING II Investigators for the ANZICS Clinical Trials Group *HumansSepsisbeta-LactamsAnti-Bacterial AgentsTreatment OutcomeLength of StayInfusions, IntravenousDrug Administration ScheduleSurvival AnalysisProspective StudiesDouble-Blind MethodAgedMiddle AgedFemaleMaleJournal article003004265010.1164/rccm.201505-0857OC2-s2.0-84946231220226311