A rapid gene expression–based blood test demonstrated diagnostic accuracy for distinguishing sepsis from noninfectious critical illness in adults admitted to the intensive care unit under Sepsis-3 criteria, according to a prospective multicenter study published in the European Journal of Clinical Microbiology & Infectious Diseases.
Early identification of sepsis remains difficult. Blood cultures are frequently negative, and commonly used biomarkers such as C-reactive protein and procalcitonin cannot reliably differentiate infection from other causes of systemic inflammation.
In this study, investigators enrolled adults admitted to seven intensive care units (ICU) in Andalusia, Spain, who had suspected sepsis at the time of ICU admission. Blood samples were collected promptly and analyzed using a rapid transcriptomic assay that measures expression of two host-response genes, PLA2G7 and PLAC8. The test generates a score from 0 to 15, categorized into four bands reflecting increasing likelihood of infection.
A total of 353 patients were included in the final analysis. At ICU discharge, 267 patients were adjudicated as having sepsis and 86 were classified as having noninfectious critical illness.
The assay achieved an area under the receiver operating characteristic curve of 0.84 for differentiating sepsis from sterile inflammation. This performance was higher than observed with C-reactive protein (CRP) (0.75) and similar to procalcitonin (PCT) (0.80).
Diagnostic performance varied by score band. In Band 4, the highest probability category, the positive predictive value for sepsis was 92% and sensitivity was 79%. In Band 1, the lowest probability category, specificity was approximately 70%. Notably, among patients whom physicians initially assessed as having a low likelihood of sepsis, those with scores in bands 1 or 2 had no final diagnosis of sepsis.
In multivariable analysis, independent predictors of sepsis included the physician’s initial clinical assessment, the gene expression score, and log-transformed PCT. CRP was not independently associated with sepsis after adjustment.
The score was not associated with disease severity or mortality. The authors noted several limitations, including restriction to adult ICU patients, lack of data on antibiotic exposure prior to ICU admission, and reliance on clinical adjudication in the absence of a definitive gold standard diagnostic test.
Source: European Journal of Clinical Microbiology & Infectious Diseases.
