Researchers at King's College London have identified a biomarker
- a biological 'fingerprint' - for sepsis in the blood, and showed
it could be possible to diagnose the condition within two hours by
screening for this biomarker at a patient's bedside.
Sepsis (sometimes referred to as 'blood poisoning') is a
life-threatening condition that arises when the body's inflammatory
response to a bacterial infection injures its own tissues and
organs. Costing the NHS over £2 billion annually, the condition
kills more people than breast and bowel cancer combined
(approximately 37,000 a year). Rapid diagnosis and treatment with
antibiotics saves lives, but as there are currently no biomarkers
in clinical use to enable fast diagnosis, it can take up to two
days to analyse samples in the laboratory.
This study highlights a possible biomarker for the rapid
diagnosis of sepsis. The work was performed in collaboration with
Cepheid, a molecular diagnostics company and developer of the
GeneXpert, which is capable of performing rapid molecular
detection.
RNA helps decode and regulate DNA. This paper investigated
microRNAs, which come in many varieties and influence disease
processes. Researchers at King's and Cepheid took samples of blood
from three groups of patients; those with sepsis, patients with
other Systemic Inflammatory Response Syndrome (that does not
respond to antibiotics), and healthy patients. From the blood
samples they were able to amplify small amounts of RNA into large
quantities to see which particular microRNAs were increased. By
using this method, the team found that a certain group of microRNAs
were more active in the sepsis patients than in the other groups,
highlighting a potential biomarker for the condition.
The study was replicated with a large group of Swedish patients
with severe sepsis, which validated the results. By using this
method of screening and analysing the blood in both studies, the
researchers were able to diagnose sepsis within two hours, with 86
per cent accuracy.
Professor Graham Lord, Director of the NIHR Biomedical Research
Centre at Guy's and St Thomas' NHS Foundation Trust and King's
College London, said: "Sepsis is a hidden killer, causing nearly a
third of all hospital deaths. Rapid antibiotic treatment for the
condition is vital - every minute counts. Yet current diagnostic
methods can take up to two days, so an accurate diagnostic test
that can be carried out at the patient's bedside is urgently
needed.
"We have for the first time identified a group of biomarkers in
the blood that are good indicators of sepsis. We have shown that it
is possible to detect these markers by screening a patient's blood
in the ward, a process which can deliver results within two hours.
This is an extremely exciting development which has the potential
to completely transform the management of this severe disease and
save thousands of lives worldwide every year. These are promising
early findings, and now we need to test this approach in a large
clinical trial."
Symptoms of sepsis are similar to other types of Systemic
Inflammatory Response Syndrome (SIRS), yet only sepsis responds to
antibiotics. It is therefore important for clinicians to be able to
distinguish sepsis from other types of SIRS as administering
antibiotics in non-sepsis cases can add pressure to the development
of antibiotic resistance. Professor Lord continued: "Not only would
an accurate diagnostic test improve outcomes for patients, but it
would contribute to tackling the ongoing problem of antibiotic
resistance by allowing clinicians to distinguish between SIRS and
sepsis and diagnose these severe conditions more accurately."
Plans for a randomised clinical trial are underway at King's
College London and Guy's and St Thomas' NHS Foundation Trust, part
of King's Health Partners Academic Health Sciences Centre.
The paper, Genome-Wide Sequencing of Cellular microRNAs Identifies a
Combinatorial Expression Signature Diagnostic of Sepsis, is
published in PLOS One.