Sepsis and Acute Care: Advancing Diagnostics Beyond Syndromic Labels

Recent key publications

Rapid pan-microbial metagenomics for pathogen detection and personalised therapy in the intensive care unit: a single-centre prospective observational study. Lancet Microbe. 2025 Oct;6(10):101174. doi: 10.1016/j.lanmic.2025.101174. Epub 2025 Oct 1.2025. Alcolea-Medina A, Snell LB, Humayun G et al.

 Link to full article:https://pubmed.ncbi.nlm.nih.gov/41045941/

Metagenomic sequencing enables pathogen detection without prior clinical suspicion, although published studies have generally reported turnaround times measured in days and provided little information about how the results affected treatment. Investigators at Guy's and St Thomas' hospitals used a single assay covering bacteria, fungi and DNA and RNA viruses on 114 respiratory samples from 74 intensive care patients over four months. Of the 107 samples that passed quality control, 94% produced a preliminary report on the same day. At 24 hours, sensitivity in lower respiratory tract specimens reached 97% for bacteria and 89% for fungi and viruses. Routine testing had missed 42 organisms detected by sequencing, and antimicrobial prescriptions were changed after 28% of results, most often by narrowing treatment. Sequencing also informed immunomodulation decisions in 20% of patients, an application not previously described. Mycobacterium tuberculosis, measles virus and parvovirus B19 were among the organisms of public health relevance. Together, the speed, breadth and accuracy of the assay allowed clinicians to act on the day the sample arrived. Earlier refinement of antibiotic treatment was the expected benefit, but the stronger case for introducing the assay into routine service lies in the unexpected organisms identified, the infection-control and surveillance signals generated and the support provided when a dysregulated inflammatory response is suspected. One rapid test therefore served both the individual patient and the wider population.

The utility of an algorithm based on procalcitonin monitoring in patients with sepsis. 
Lab Med. 2025 May 9;56(3):220-229. doi: 10.1093/labmed/lmae074. de Lózar de la Viña A, Andrade Vivero G, Palencia Herrejón E et al. 

 Link to full article:https://pubmed.ncbi.nlm.nih.gov/39446602/

Sepsis remains one of the principal causes of death in intensive care, and early recognition of patients at risk of deterioration carries clear clinical importance. De Lózar de la Viña and colleagues developed an algorithm based on serial procalcitonin measurements taken at admission and after 6, 12, 24 and 36 hours. It classifies patients with sepsis into good, poor or inconclusive prognostic categories within the first day and a half. A baseline value below 1 ng/mL proved a useful threshold for identifying low-risk patients, whose outcomes were generally favourable. Validation in 43 intensive care patients yielded a sensitivity of 80.0% and specificity of 86.8% for 28-day mortality, outperforming SAPS 3 and approaching baseline SOFA. In the development cohort, the investigators calculated that 76.37% of procalcitonin requests could have been avoided without losing prognostic information. This points to potential cost savings if testing is reduced for patients whose prognosis already appears good. Prospective confirmation in much larger, multicentre cohorts is urgently needed.

Nanosensor-Based Pattern-Generating Probe Accelerates Sepsis Diagnosis. 
ACS Nano. 2025 Nov 25;19(46):40061-40071. doi: 10.1021/acsnano.5c14974. Epub 2025 Nov 14. Ni W, Huang H, Yue Q et al.

 Link to full article:https://pubmed.ncbi.nlm.nih.gov/41237320/

Every hour of delay before appropriate antibiotics are administered increases sepsis mortality by up to 8%, yet identifying the causative organism still takes considerably longer. Ni and colleagues assembled three amphiphilic molecules, each carrying a different fluorophore, into a single nanostructure. Energy transfer between the dyes produced six readable channels simultaneously. A 30-second measurement distinguished 24 common clinical pathogens, with blind-test accuracies of 96.9% in water, 90.6% in urine and 86.5% in serum. The system also resolved bacterial load, mixtures of two organisms and Gram status. When applied to serum samples from 51 patients with sepsis and ten healthy controls, a multilayer perceptron classified the five sample types with 93.6% test accuracy. The analysis was completed in under 30 seconds. The authors note that the concentrations typically found in clinical sepsis are below the array's current direct detection limit, suggesting that the signal probably reflects broader changes in serum composition. They propose group-specific design of the sensing molecules and combinatorial chemistry screening as ways to improve sensitivity and accuracy, with infectious disease and cancer detection as the intended clinical applications. Importantly, this remains a proof of concept and requires further validation.

The molecular ICU: a primer on omics, informatics and the future of precision critical care. 
Crit Care. 2026 Jul 6;30(1):356. doi: 10.1186/s13054-026-06169-5.; 30. Van Nynatten LR, Raheel H, Basmaji J et al.

 Link to full article: https://pubmed.ncbi.nlm.nih.gov/42410654/

Neutral trials have accumulated in critical care for decades, largely because syndromic labels such as sepsis and acute respiratory distress syndrome group together patients whose underlying biology differs widely, causing genuine treatment effects to be obscured. The biology of critical illness is complex and can change from hour to hour, and no single biomarker can capture it. This comprehensive review argues that the most useful unit for translation is neither a single analyte nor a list of several thousand omics features, but a compact signature of a coordinated biological pathway. Drawing on transcriptomic, proteomic and metabolomic research, the authors describe how pathway enrichment, network methods and integration across molecular layers can define subgroups with a defensible biological mechanism. Reanalyses of VANISH, HARP-2 and PROWESS-SHOCK revealed treatment responses that syndromic labels had concealed, while platforms including PANTHER, TRAITS and TIGERS now assign patients according to molecular criteria at enrolment. Notably, the same pathway signatures indicate candidate drugs already licensed for other conditions. Designing trials as though a syndromic label represents a single biology can keep useful treatments hidden and expose patients to interventions from which they are unlikely to benefit. The molecular intensive care unit is within reach; the challenge now lies in implementation.

Clinical evaluation of the SeptiScore biomarker for the diagnosis of healthcare-associated infections in critically ill trauma patients: a multicenter derivation and validation cohort study. 
BMC Anesthesiol. 2026 Jul 10. doi: 10.1186/s12871-026-04088-0. Online ahead of print. Bouras M, Neutre L, Douarec C et al.

 Link to full article:https://pubmed.ncbi.nlm.nih.gov/42432516/

Distinguishing a healthcare-associated infection from sterile inflammation after severe injury remains challenging at the bedside because procalcitonin and C-reactive protein increase in both conditions. Bouras and colleagues evaluated SeptiScore, an automated assay that measures PLAC8 and PLA2G7 transcripts in whole blood and returns a result within an hour. They studied 113 samples from trauma patients who met systemic inflammatory response criteria and had haemodynamic failure. Samples were taken when infection was clinically suspected and before microbiological results were available. Scores were higher during infection than during trauma-related inflammation. Among 29 patients sampled both before and after infection began, the value increased by a median of 2.4 points. A cut-off of 6.7 in the derivation cohort gave 84% sensitivity and 66% specificity, with an area under the curve of 0.79, higher than that of procalcitonin, C-reactive protein and leucocyte count. The same cut-off performed consistently in a separate cohort, although only ten infections were available for analysis. Host-response profiling appears worth pursuing in inflammatory settings such as severe trauma, but the evidence remains preliminary. Adequately powered multicentre studies are needed to confirm the diagnostic findings and establish whether using SeptiScore to guide patient management improves outcomes.

Essential laboratory tests in emergencies; on behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Committee on Preparation of Laboratories for Emergencies (C-PLE). 
Clin Chem Lab Med. 2026 May 6;64(9):1930-1938. doi: 10.1515/cclm-2026-0577. Print 2026 Aug 24.; 64:1930-1938. Lippi G, Alkhazashvili M, Banuls Laetitia MY et al.

 Link to full article: https://pubmed.ncbi.nlm.nih.gov/42083866/

Wars, climate-driven disasters and prolonged political instability damage laboratory infrastructure in the very settings where triage, resuscitation and outbreak detection depend on it. The Committee on Preparation of Laboratories for Emergencies, part of the European Federation of Clinical Chemistry and Laboratory Medicine, asked its members which tests a laboratory operating under austere conditions cannot do without. Twenty of the 24 members returned ratings across four priority tiers. Full blood count, sodium, potassium and chloride, glucose, lactate, blood gases with ionised calcium, urinalysis and ABO and RhD typing were rated essential. Urea or creatinine, prothrombin time with international normalised ratio, activated partial thromboplastin time, aminotransferases and cardiac troponins were placed in the critical tier. C-reactive protein, D-dimer, rapid tests for infectious diseases and procalcitonin were considered supportive. Urine pregnancy testing, bilirubin and lipase were suggested as candidates for later inclusion. Prioritising tests in this way balances clinical value against what a damaged or improvised laboratory can realistically deliver. It should support faster triage, inform life-saving treatment and underpin the public health response. The list complements documents from the WHO, NATO and CLSI and is intended to be adapted to local epidemiology, available supplies and the specific emergency.