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

Abdul-Aziz, Mohd H., Sulaiman, Helmi, Mat-Nor, Mohd-Basri, Rai, Vineya, Wong, Kang K., Hasan, Mohd S., Abd Rahman, Azrin N., Jamal, Janattul A., Wallis, Steven C., Lipman, Jeffrey, Staatz, Christine E. and Roberts, Jason A. (2016) 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. Intensive Care Medicine, 1-11. doi:10.1007/s00134-015-4188-0


Author Abdul-Aziz, Mohd H.
Sulaiman, Helmi
Mat-Nor, Mohd-Basri
Rai, Vineya
Wong, Kang K.
Hasan, Mohd S.
Abd Rahman, Azrin N.
Jamal, Janattul A.
Wallis, Steven C.
Lipman, Jeffrey
Staatz, Christine E.
Roberts, Jason A.
Title 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
Journal name Intensive Care Medicine   Check publisher's open access policy
ISSN 1432-1238
0342-4642
Publication date 2016-01-11
Sub-type Article (original research)
DOI 10.1007/s00134-015-4188-0
Open Access Status Not Open Access
Start page 1
End page 11
Total pages 11
Place of publication Heidelberg, Germany
Publisher Springer
Collection year 2017
Formatted abstract
Purpose:
This study aims to determine if continuous infusion (CI) is associated with better clinical and pharmacokinetic/pharmacodynamic (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 primary 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 survival, 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 participants. 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 difference in 14-day or 30-day survival between the treatment arms.
Conclusions:
In critically ill patients with severe sepsis not receiving RRT, CI demonstrated higher clinical cure rates and had better PK/PD target attainment compared to IB dosing of beta-lactam antibiotics. Continuous beta-lactam infusion may be mostly advantageous for critically ill patients with high levels of illness severity and not receiving RRT.
Keyword Antibiotics
Critically ill
Intermittent bolus
Pharmacodynamics
Pharmacokinetics
Prolonged infusion
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Published online 11 January 2016

Document type: Journal Article
Sub-type: Article (original research)
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