A protocol for a multicentre randomised controlled trial of continuous beta-lactam infusion compared with intermittent beta-lactam dosing in critically ill patients with severe sepsis: the BLING II study.

Author(s): Dulhunty JM(1), Roberts JA, Davis JS, Webb SA, Bellomo R, Gomersall C, Shirwadkar C, Eastwood GM, Myburgh J, Paterson DL, Starr T, Udy AA, Paul SK, Lipman J; Australian and New Zealand Intensive Care Society Clinical Trials Group; Australasian Society for Infectious Diseases Clinical Research Network.

Affiliation(s): Author information: (1)Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Joel_Dulhunty@health.qld.gov.au

Publication date & source: 2013, Crit Care Resusc. , 15(3):179-85

BACKGROUND AND RATIONALE: Beta-lactam antibiotics are largely administered by bolus dosing, despite displaying time-dependent pharmacokinetics and pharmacodynamics and there being a strong rationale for continuous administration. The randomised controlled trials conducted to date comparing the mode of betalactam administration have been inconclusive and limited by non-equivalent dosing, unblinded administration and small sample sizes. OBJECTIVE: A multicentre, randomised controlled trial (the Beta-lactam Infusion Group [BLING] II study) is currently under way, comparing continuous infusion to standard bolus administration of beta-lactam antibiotics in critically ill patients, independent of dose. DESIGN, SETTINGS, PARTICIPANTS AND INTERVENTIONS: BLING II is a Phase IIB, double-blinded, randomised controlled trial recruiting 420 intensive care unit patients with severe sepsis to receive one of three beta-lactam study antibiotics (ticarcillin-clavulanate, piperacillin- tazobactam or meropenem) by either continuous infusion or intermittent bolus administration. MAIN OUTCOME MEASURES: The primary outcome is ICUfree days at Day 28. Secondary outcomes include 90-day survival, clinical cure 14 days after study antibiotic cessation, organ failure-free days at Day 14 and duration of bacteraemia. RESULTS AND CONCLUSIONS: The study started in July 2012 and will provide clinical evidence as to whether continuous infusion of beta-lactam antibiotics is superior to intermittent bolus administration in critically ill patients with severe sepsis. A Phase III study powered for a survival end point may be justified, based on the results of our study.