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.
OBJECTIVE
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.
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.


METHODS
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.


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.
Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Joel_Dulhunty@health.qld.gov.au
Joel M
JM
Dulhunty
Jason A
JA
Roberts
Joshua S
JS
Davis
Steven A R
SA
Webb
Rinaldo
R
Bellomo
Charles
C
Gomersall
Charudatt
C
Shirwadkar
Glenn M
GM
Eastwood
John
J
Myburgh
David L
DL
Paterson
Therese
T
Starr
Andrew A
AA
Udy
Sanjoy K
SK
Paul
Jeffrey
J
Lipman
D000328:Adult; D000368:Aged; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy*; D016896:Treatment Outcome; D047090:beta-Lactams / Q000008:administration & dosage*
D047090:beta-Lactams