Beta-lactam antibiotics infusion group study - BLING III


Beta-lactam antibiotics are commonly used to treat life-threatening infections in critically ill patients. As a class of antibiotics, beta-lactams are known as time-dependent antibiotics because they have their greatest effect when the antibiotic concentration in the blood remains above a critical level (dependent on the organism) for the duration of the course.

Continuous infusion of beta-lactams has been shown to more consistently achieve these time-dependent pharmacodynamic endpoints than the standard practice of bolus dosing. However, the relatively small randomised controlled trials to date have not reported improved clinical outcomes, such as resolution of infection or lower mortality, with the use of continuous infusion

A prospective, multicentre, double-blind, double-dummy, phase II RCT (BLING II) was conducted in 25 ICUs in Australia, New Zealand and Hong Kong. While there was no significant difference in the primary endpoint, it found an absolute difference in hospital mortality and a similar directional trend in ICU discharge. On that basis conducting a large multicentre, controlled trial (RCT) to determine whether continuous or intermittent infusion of these antibiotics results in decreased clinical mortality outcomes (BLING III).


To conduct a multicentre randomised, controlled trial (RCT) to determine whether continuous infusion of a beta-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all cause Day 90 mortality compared with intermittent beta-lactam antibiotic infusion in critically ill patients.

Design: The BLING III study is a prospective, multicentre, open, phase III, RCT. 7000 participants from 100 sites, commenced on one of two beta-lactam antibiotics (piperacillin-tazobactam or meropenem) will be randomised to receive the beta-lactam antibiotic via either continuous infusion or intermittent infusion over 30 minutes for the treatment course or 14 days while in the ICU and will be followed up for 90 days after randomisation.

Inclusion Criteria: Patients will be included if they have an infection with organ failure, are expected to be in ICU the day after tomorrow, have commenced on piperacillin-tazobactam or meropenem and the clinician considers intermittent infusion or continuous infusion equally appropriate.

Exclusion Criteria:

Patients are excluded if they are not younger than 18 years of age, have received piperacillin-tazobactam or meropenem for greater than 24 hours, have a known allergy to penicillin, require renal replacement therapy, will not survive current illness or the patient / relative / physician  are not committed to advanced life-support and have been enrolled in BLING III previously.


Recruitment commenced in March 2017.  Currently in the recruitment phase. The study has sites from Australia, New Zealand, United Kingdom, Belgium, France, Sweden and Malaysia.