Poster Presentation 15th Lorne Infection and Immunity 2025

MicroRNA sepsis biomarkers: distinguishing bacterial aetiology from non-infectious inflammation in critically ill Australian patients (#329)

Carlos Henrique Miranda Rodrigues 1 , Jenny Su 1 , Kerina Denny 2 , Cheryl Fourie 3 , Krispin Hajkowicz 3 , Melissa Lassig-Smith 3 , James McCullough 2 , Michael C Reade 3 , Cameron R Stewart 1 , Janine Stuart 3 , Alexis Tabah 4 , Jeffrey Lipman 3 , Ryan J Farr 1
  1. Health and Biosecurity at the Australian Centre for Disease Preparedness (ACDP), CSIRO, Geelong, Victoria, Australia
  2. Gold Coast University Hospital, Gold Coast, QLD
  3. Royal Brisbane and Women's Hospital, Brisbane, QLD
  4. Redcliffe Hospital, Redcliffe, QLD

Sepsis is a life-threatening condition that is responsible for ~20% of all global deaths each year. For every hour antibiotic treatment is delayed in bacterial sepsis, the odds of mortality increase by 9% [1]. The reference standard tests for bacterial sepsis (blood cultures) take 24-48 hours to complete. Consequently, antibiotics are often used empirically in the absence of a confirmed bacterial diagnosis. Several biomarker tests have been developed to more rapidly distinguish bacterial sepsis from non-infectious systemic inflammation, including C-reactive protein (CRP) and procalcitonin (PCT), with varying success.

MicroRNAs (miRNAs) are short non-coding RNAs that function as post-transcriptional gene regulators and are promising biomarkers of infectious diseases [2]. To test their utility in identifying bacterial sepsis, we recruited and sampled plasma from adult ICU patients at the Royal Brisbane and Women’s, Redcliffe, and Gold Coast University Hospitals (with ethics approval from Metro North Health and CSIRO). Patients were grouped retrospectively into aseptic inflammation (n=27), blood culture positive sepsis (BCpos, n=23), or blood culture negative sepsis (BCneg, n=30). Of the 632 miRNAs identified in these samples via NGS, machine learning identified a 3-miRNA signature (3-miR) that distinguished BCpos patients from systemic inflammation with an ROC area of 0.93 [95% CI, 0.852–1.0]. This signature outperformed CRP (aROC 0.72 [0.608–0.832]) and was comparable to PCT (aROC 0.98 [0.938–1.0]). Both CRP and PCT displayed a lower aROC (0.63 [0.486–0.774] and 0.7 [0.565–0.835] respectively) in distinguishing BCneg patients, while 3-miR displayed sustained performance (aROC 0.96 [0.908–1.0]), suggesting that this signature may offer increased sensitivity in distinguishing bacterial sepsis.

This pilot study highlights the potential of miRNA biomarkers in differentiating bacterial sepsis from other causes of systemic inflammation, thereby increasing clinicians’ diagnostic confidence, reducing unnecessary antibiotic use and improving patient outcomes.

  1. [1] Liu VX, Fielding-Singh V, Greene JD, Baker JM, Iwashyna TJ, Bhattacharya J, Escobar GJ. The Timing of Early Antibiotics and Hospital Mortality in Sepsis. Am J Respir Crit Care Med. 2017 Oct 1;196(7):856-863. doi: 10.1164/rccm.201609-1848OC. PMID: 28345952; PMCID: PMC5649973.
  2. [2] Tribolet L, Kerr E, Cowled C, Bean AGD, Stewart CR, Dearnley M, Farr RJ. MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing. Front Microbiol. 2020 Jun 3;11:1197. doi: 10.3389/fmicb.2020.01197. PMID: 32582115; PMCID: PMC7286131.