WA first for sepsis testing

Sepsis patients could experience better outcomes thanks to new WA research using blood plasma metabolic phenotyping to diagnose the condition quickly and accurately.

The results are available within one hour of blood collection, compared to current methods which require culturing pathogens and can take days to confirm. 

The study involved the collection of blood plasma samples from 152 ICU patients in WA hospitals and lead author, Dr Sam Lodge, from Murdoch University’s Australian National Phenome Centre, said identifying metabolic signatures were the key to the breakthrough.  

“We found that non-sepsis, sepsis, and septic shock ICU patients have differential metabolic signatures, which can be used to diagnose patients quickly – within one hour of blood collection,” Dr Lodge said.  

“Sepsis is a life-threatening condition when your body has an extreme response to an infection. It needs immediate medical attention, or it can cause death or permanent damage to your body – a timely diagnosis has the potential to significantly reduce mortality rates. 

“We demonstrate that a subset of 15 metabolites can successfully stratify patients into the correct sepsis clinical outcome upon admission into ICU.” 

Despite notable improvements in the delivery of intensive care in recent years, severe sepsis and septic shock remain a significant clinical problem with a substantial morbidity, mortality, and economic burden. 

The diagnosis of sepsis relies on a clinical assessment of the likelihood of infection and associated systemic features and is subsequently dependent on the positive identification of a pathogenic organism using standard clinical pathogen culturing, which occurs in only a minority of patients.  

Around 20% of sepsis patients in ICU will progress to septic shock, which is associated with multi organ failure and 9.8% mortality. Critically, the mortality rate of patients with septic shock can increase 8% for every hour delay in antimicrobial therapy. 

“Pre-interventional metabolic phenotyping can enable prediction of interventional outcomes such as toxicity, drug metabolism, and anti-cancer drug efficacy in animals and humans,” Dr Lodge said. 

“Since the biomarkers that are currently used to identify sepsis are inadequate for discriminating between sepsis and septic shock patients in ICU, we applied a multiplatform metabolic profiling approach to see whether plasma profiles could be used to differentiate patients with no sepsis, sepsis, and septic shock at admission into ICU — regardless of admission route or type.” 

Four lipoproteins (specifically four phosphatidylcholine species produced by the liver) were found at higher concentrations in the group without sepsis versus the sepsis and septic shock group and were markedly reduced in septic shock patients in comparison to sepsis patients on admission into ICU.  

Previously, studies have reported that high density lipoprotein levels at time of admission to ICU were more predictive of 28-day mortality than any other measured parameter, and the study showed that while HDL4 concentrations were reduced in all patients at admission into the ICU, patients who were diagnosed with sepsis and septic shock had particularly low HDL4 levels. 

“HDL has been shown to suppress the inhibitory effect of high concentrations of lipopolysaccharide binding protein (LPS) prior to HDL binding to LPS, which also serves to augment monocyte activity and control the response to sepsis,” Dr Lodge said. 

In contrast to the lower levels of HDL in patients with sepsis and septic shock, plasma neopterin levels were elevated.  

Two cholesterol esters were also significantly different between the sepsis and septic shock patients at admission into ICU.