It’s all about the details: how well-designed research improves clinical care

Developments in healthcare often take place bit by bit, study by study, as clinician scientists build an evidence base through research.

But how can subtle improvements be detected and relied upon?

It all boils down to the right study design, careful data collection and appropriate interpretation.

Case in point is a new – and very large – international study investigating antibiotic treatment for patients with sepsis.

In collaboration with colleagues at The George Institute for Global Health, Professor Sandra Peake from the Department of Intensive Care Medicine at The Queen Elizabeth Hospital (TQEH) recently published the results of the study.

The research answers important questions regarding care for patients who are seriously ill with sepsis.

“The results show that giving continuous antibiotics to sepsis patients is likely to be the best way to kill bacteria and save lives,” says Professor Peake.

Subtle but important improvement

Sepsis is a life-threatening condition affecting 55,000 Australians each year and results in 8,700 deaths.

Overwhelming infections such as pneumonia, abdominal infection and urinary tract infection are the most common causes of sepsis.

“Sepsis causes a dysregulated immune response and multiple organ dysfunction,” says Professor Peake.

“In patients that do survive, forty percent have long-term, often life-changing physical, cognitive and psychological impacts.”

Treating sepsis requires early and appropriate antibiotics, and beta-lactams are often the first-line antibiotics administered.

“We had data from observational and small randomised trials which suggested that giving these antibiotics by a continuous infusion over 24 hours – rather than the traditional method which involves intermittent doses two to four times per day – may increase the ability of these drugs to kill the bacteria,” says Professor Peake.

The new study, known as BLING-III, aimed to rigorously assess continuous versus intermittent infusion of beta-lactam antibiotics for patients with sepsis.

“Our study included 7,031 critically ill adult patients with sepsis in 104 intensive care units in Australia, Belgium, France, Malaysia, New Zealand, Sweden and the United Kingdom,” says Professor Peake.

The results were subtle but clear once study outcomes took patient variables into account, such as sex, severity of illness and operation type.

“We reported a significant reduction in mortality of 2.2% associated with continuous infusion,” Professor Peake says.

In real terms, this translates into two extra lives saved for every 100 patients treated.

Other improvements were recorded as well.

“Continuous infusion was also associated with a significant improvement in clinical cure and no increase in the development of multi-resistant organisms,” Professor Peake says.

Multi-resistant organisms are bacteria that are no longer able to be treated by certain antibiotics, and present increased threat for patient recovery.

The bigger picture

Data from the BLING-III trial were included in a larger, co-published meta-analysis.

“The results from this broader analysis that includes the results of other trials strengthen the case for continuous antibiotic infusion to reduce death from sepsis,” says Professor Peake.

“It’s now highly probable that continuous infusion is better than intermittent infusion to treat sepsis.”

Funded by the Medical Research Future Fund, Professor Peake is currently conducting further research into the optimal treatment of sepsis.

“International sepsis guidelines recommend that early resuscitation includes large volumes of fluid administration to treat shock,” she says.

“Our trial is evaluating whether a more restrictive fluid strategy combined with the early administration of medications to support patient blood pressure is better than usual care.”