Mohd H. Abdul-Aziz Helmi Sulaiman Mohd-Basri Mat-Nor Vineya Rai Kang K. Wong Mohd S. Hasan Azrin N. Abd Rahman Janattul A. Jamal Steven C. Wallis Jeffrey Lipman Christine E. Staatz Jason A. Roberts Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis Received: 19 November 2015 Accepted: 10 December 2015 Published online: 11 January 2016 Ó Springer-Verlag Berlin Heidelberg and ESICM 2015 Electronic supplementary material The online version of this article (doi:10.1007/s00134-015-4188-0) contains supplementary material, which is available to authorized users. M. H. Abdul-Aziz ( ) ) Á S. C. Wallis Á J. Lipman Á J. A. Roberts ( ) ) Burns, Trauma and Critical Care Research Centre, Level 3, Ned Hanlon Building, Royal Brisbane and Women’s Hospital, The University of Queensland, Herston, QLD 4029, Australia e-mail: mohd.abdulaziz1@ uqconnect.edu.au Tel.: ?61736361847 J. A. Roberts e-mail: j.roberts2@uq.edu.au Tel.: ?61736361847 M. H. Abdul-Aziz Á A. N. Abd Rahman School of Pharmacy, International Islamic University of Malaysia, Kuantan, Pahang, Malaysia H. Sulaiman Infectious Diseases Unit, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia M.-B. Mat-Nor Department of Anaesthesiology and Intensive Care, School of Medicine, International Islamic University of Malaysia, Kuantan, Pahang, Malaysia V. Rai Á K. K. Wong Á M. S. Hasan Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia A. N. Abd Rahman Á C. E. Staatz Á J. A. Roberts School of Pharmacy, The University of Queensland, Brisbane, Australia J. A. Jamal Department of Pharmacy, Hospital Tengku Ampuan Afzan, Kuantan, Malaysia J. Lipman Á J. A. Roberts Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Australia C. E. Staatz Australian Centre of Pharmacometrics, Brisbane, Australia Abstract Purpose: This study aims to determine if continuous infusion (CI) is associated with better clinical and pharmacokinetic/phar- macodynamic (PK/PD) outcomes compared to intermittent bolus (IB) dosing in critically ill patients with severe sepsis. Methods: This was a two-centre randomised controlled trial of CI versus IB dosing of beta- lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The pri- mary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post- randomisation, 14- and 30-day sur- vival, and time to white cell count normalisation. Results: A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p \ 0.043) than IB partici- pants. PK/PD target attainment rates were higher in the CI arm at 100 % fT [MIC than the IB arm on day 1 (97 versus 70 %, p \ 0.001) and day 3 (97 versus 68 %, p \ 0.001) post- randomisation. There was no differ- ence in 14-day or 30-day survival between the treatment arms. Conclu- sions: In critically ill patients with severe sepsis not receiving RRT, CI demonstrated higher clinical cure Intensive Care Med (2016) 42:1535–1545 DOI 10.1007/s00134-015-4188-0 ORIGINAL