No single test diagnoses sepsis. Other diagnostic studies include microbiological cultures, culture-independent pathogen detection, host-response sepsis-likelihood assays, rapid host biomarkers, and advanced hemodynamic monitoring. Routine chemistries, lactate, CBC, and coagulation studies belong in Laboratory findings; SOFA/qSOFA belongs in Classification; echocardiography and fluid-responsiveness testing belong in the echocardiography/ultrasound microchapter.^[1]

A pathogen is identified in approximately 60–70% of patients with sepsis, whereas blood cultures are positive in only approximately 10–20%. The 2026 Surviving Sepsis Campaign (SSC) strongly recommends collecting blood cultures as soon as possible and ideally before antimicrobial therapy, without delaying antimicrobials in unstable patients.^[1]

Blood-culture yield depends on pretest probability, the number of culture sets, blood volume, use of anaerobic bottles, and prior antimicrobial exposure. Approximately 10 mL of blood per bottle is used for adult blood cultures. The yield is higher in septic shock, with bacteremia detected in at least 50% of patients in some high-risk populations. Blood-culture positivity decreased from 31.4% to 19.4% when cultures were obtained at a median of 70 minutes after antimicrobial administration.^[1]

Two-site sampling is traditional; one study cited by the SSC reported sensitivity increasing from 91.5% with one site to 99.3% with two sites. However, 2025 German national guidance favors single-site sampling, reflecting ongoing practice variation.^[1]

Repeat blood cultures should be obtained to document clearance in patients with Staphylococcus aureus bacteremia, Staphylococcus lugdunensis bacteremia, or Candida bloodstream infection.^[1]

The 2026 SSC conditionally recommends rapid molecular or syndromic pathogen-detection tests in selected patients rather than routinely in all patients with sepsis. When used in isolation, rapid diagnostic testing has shown little or no mortality benefit (RR 1.03; 95% CI 0.78–1.13); clinical benefit is more apparent when rapid diagnostics are paired with an effective antimicrobial-stewardship strategy.^[1][2][3]

Metagenomic next-generation sequencing (mNGS), including microbial cell-free DNA sequencing, can identify pathogens at substantially higher rates than conventional culture in selected patients with sepsis. Across published cohorts, pathogen positivity has been approximately 3–4 times higher than with culture. Interpretation remains limited by cost, turnaround time, detection of organisms of uncertain clinical significance, and lack of standardized interpretation; results require clinical correlation.^[4][5][6][7]

Rapid direct-from-blood nucleic-acid amplification tests, including T2Bacteria and T2Candida, can provide pathogen detection within hours but should be used concurrently with blood cultures because cultures provide broader organism coverage and antimicrobial susceptibility information.^[8]

FDA-cleared host-response assays include monocyte distribution width (MDW), IntelliSep, SeptiCyte Rapid/TriVerity, Sepsis ImmunoScore, and pancreatic stone protein (PSP). These assays provide a graded probability of sepsis rather than a binary diagnostic result. The 2026 SSC did not recommend any specific host-response assay because of cost and insufficient outcome data. Their incremental diagnostic value is limited when the pretest probability of sepsis is already very high.^[1]

MDW is reported as part of an activated CBC with differential when the assay is available.^[1]

Procalcitonin, C-reactive protein (CRP), and presepsin are adjunctive biomarkers rather than stand-alone rule-in tests for sepsis. Their principal practical value is as part of an overall clinical assessment, including support for antimicrobial de-escalation when interpreted with the clinical course and other microbiological data.^[8]

Procalcitonin can increase in severe viral illness. CRP responses may be blunted by neutropenia, immunosuppression, or nonsteroidal anti-inflammatory drug exposure; these limitations should be considered when interpreting results.^[8]

Advanced hemodynamic monitoring may be considered when noninvasive assessment is insufficient in refractory shock. Transpulmonary thermodilution and pulmonary artery catheterization can characterize cardiac output and its determinants in selected patients. The pulmonary artery catheter has a narrower role, particularly in patients with right ventricular failure or pulmonary hypertension.^[1]

The 2026 SSC found insufficient evidence to recommend for or against minimally invasive or noninvasive cardiac-output monitoring. These techniques should therefore be selected according to the clinical question, available expertise, and patient physiology rather than used routinely in all patients with sepsis.^[1]