Sepsis

What is sepsis?

Sepsis is not a particular infection. It is the way the body responds to one when that response goes wrong and starts damaging its own organs. It can start from pneumonia, a urinary, abdominal or skin infection, or an infected line, and it can be caused by bacteria, fungi or viruses.

The current definition is the Sepsis-3 consensus (Singer and colleagues, JAMA, 2016): life-threatening organ dysfunction caused by a dysregulated host response to infection. In practice, organ dysfunction is identified as an acute rise of 2 or more points in the SOFA score from baseline. Septic shock is the most severe subset: the patient needs vasopressors to keep mean arterial pressure at 65 mmHg or above and has a lactate above 2 mmol/L despite adequate fluid resuscitation.

The burden is huge. A Global Burden of Disease analysis (Rudd and colleagues, The Lancet, 2020) estimated 48.9 million cases and 11 million sepsis-related deaths in 2017, close to one in five deaths worldwide.

How it is investigated

Sepsis is a clinical diagnosis. Early antibiotics and organ support come first, and sampling must not delay them. Microbiology then aims to identify the organism and refine treatment:

• Blood culture: still the reference standard. It isolates the organism and allows susceptibility testing, but it is slow and can be negative, especially after antibiotics have started.
• Molecular tests: PCR panels on positive blood cultures or directly on blood.
• Clinical metagenomics: sequences the genetic material in a sample without targeting a single pathogen. It can detect hard-to-culture organisms and antimicrobial resistance genes. It is complementary: detecting DNA does not always mean active infection, and the result must be read against the clinical picture.

Example

A patient is admitted to intensive care with septic shock of unclear source. Blood cultures are taken and empirical antibiotics started straight away. After 72 hours the cultures remain negative and the patient is not improving. The intensivist requests metagenomic testing on blood, which detects DNA from an organism consistent with the clinical suspicion and a relevant resistance gene. With the microbiology team, she reviews the antibiotic regimen. The final decision draws on all the evidence, not sequencing alone.

Sepsis at Xenogene

Xenogene’s AMC CRITICAL sequences venous blood in critical situations. According to the product sheet, it identifies microorganisms (bacteria, viruses, fungi, mycobacteria and parasites) together with resistance genes and plasmids, and its listed indications include sepsis of unknown origin, septic shock and cases with negative blood cultures. The sheet advises drawing the sample before antibiotics where possible, without ever delaying treatment. It complements blood culture and is requested and interpreted by the responsible medical team.