Does antibiotic delivery method improve health outcomes?
Could the simple step of changing the way antibiotics are delivered – by administering a continuous dose daily rather than more frequent standard doses – result in significantly improved patient outcomes for patients with sepsis?
Dr Joel Dulhunty has been involved in all three RBWH ICU projects
In what is the culmination of years of bench-to-bedside research, the results of a 7,000-patient international study looking into a different method of administering antibiotics will be released in 2024.
Professor Jeffrey Lipman, working with Professor Jason Roberts, Dr Joel Dulhunty, Therese Starr and others, has spearheaded this research question over the last 14 years, primarily out of the Intensive Care Unit (ICU) at the Royal Brisbane and Women’s Hospital (RBWH).
The question is a vital one considering severe sepsis is a major cause of mortality worldwide.
In April 2023, the BLING III Study completed recruitment and 90-day follow-up worldwide. The study is an International Randomised Clinical Trial comparing standard bolus dosing of piperacillin/tazobactam or meropenem with the same dose administered as a continuous infusion.
Optimising antibiotic administration has been on Professor Lipman’s radar since the 1990s, when he conducted a study in Soweto, South Africa involving administration of another type of antibiotics (aminoglycosides) in more than 300 patients. The single daily dosing resulted in improved outcomes and encouraged Professor Lipman to continue antibiotic dosing research in other areas. In 2010 he brought together a team of expert clinicians to look at continuous infusion of beta-lactam antibiotics in critically ill patients. This turned out to be the beginning of 14 years of research activity on the topic in partnership between the RBWH ICU and other research centres.
An initial trial involving 60 patients, named the Beta-Lactam Infusion Group (BLING) I study, tested feasibility.
The 432-patient BLING II trial came next. With its coordination hub at RBWH’s ICU, it was carried out across 25 sites in Australia and New Zealand.
Dr Dulhunty has been involved in all three BLING projects.
“This stepwise program of research, which started with the small BLING I pilot study and has now ended with the massive international phase III trial, has been necessary to answer the question that has been debated since the first laboratory evidence showed that bacteria were better killed by this important group of antibiotics when exposed to the drug for longer periods of time — can we administer beta-lactam antibiotics in a better way?” Dr Dulhunty said.
“Unfortunately, small studies just don’t have the power to show whether survival can be improved by the way we administer antibiotics. This is why BLING III was needed.”
When BLING III started in 2015, after a successful National Health and Medical Research Council grant, it was determined it would require 7,000 study participants to provide sufficient evidence to answer the research question. To undertake an operation of that scale, the RBWH team engaged with The George Institute for Global Health, who became the study sponsor.
New research sites were established internationally with the study conducted in the United Kingdom, Belgium, France, Sweden, and Malaysia, as well as in Australia and New Zealand. With RBWH’s ICU at the heart of the program, the team has fostered engagement with its worldwide partners and proven the hosptial’s ability to host multi-centre research.
The results of the research will be published in 2024.