Significant challenges persist in managing sepsis in POC settings across diverse healthcare systems and resource settings. Late presentation and delayed or missed diagnosis, which occur in HICs and are more pronounced in LMICs, result in negative health outcomes. Clinical symptoms of sepsis often present like other conditions.  There is no single definitive diagnostic test, which can lead to variable triage and recognition. Furthermore, diversity in patient populations from varying health conditions and immune responses, and the prevalence of healthcare-associated infections (HAIs) are major factors in treatment failure and rapid progression to sepsis and septic shock.

Collaborative international initiatives, like the Surviving Sepsis Campaign (2021) and National Institute for Health and Care Excellence (NICE) updates to the NG51 guideline (2024) have focused on evidence-based guidelines and practices to address high sepsis mortality rates stemming from persistent delays in recognition, diagnosis and treatment. Given that 918,000 patients are hospitalised each year in the UK with ‘suspicion of sepsis’, and that 80-87% of sepsis hospitalisations in the US present from the healthcare community setting, there are opportunities for early identification and response from patient-provider encounters in the time frame before sepsis hospitalisation. Recognising sepsis early in the disease continuum, when clinical symptoms first manifest – rapid heart rate, fever, abnormal white blood cell count in response to infection – is essential to timely therapy to halt the cascade to multi-organ dysfunction and failure. This narrow window of opportunity also presents challenges. Treatment delays dramatically worsen outcomes; one analysis shows patients admitted to intensive care units (ICUs) with severe sepsis have a 39.8% risk of death, each hour of delay in antibiotic administration contributes up to a 9% increase in mortality.

The standard strategy of immediate, empiric, broad-spectrum antibiotic therapy – necessary for severe sepsis or shock – can inadvertently contribute to antimicrobial overuse and resistance, leading to severe infections, extended hospital stays and increased mortality. Antibiotic stewardship has been defined in consensus agreement as ‘coordinated interventions to improve and measure the appropriate use of antibiotic agents through selection of the optimal drug regimens including dosing, duration of therapy and route of administration’. Key guidelines are highlighted in the WHO’s Global Action Plan and LMIC toolkit, and the UK’s Antimicrobial Prescribing and Stewardship (APS) Competency Framework. These efforts complement existing standards, aiding clinicians in enhancing clinical outcomes. General practitioners prescribe up to 90% of outpatient antibiotics, offering opportunities for stewardship to ensure responsible and effective use. Multifaceted interventions for sepsis, including de-escalation measures and stewardship, alongside PCT use are proven to be effective in reducing antibiotic overuse, aiding decision-making and guiding therapy duration.

Several alert and triage systems, screening scores and intervention strategies have been incorporated to assist clinicians in optimising early recognition and management. Consensus guidelines (2016) in diagnosis called for qSOFA, with 2021 guidelines favouring NEWS over MEWS due to efficiency and reliability in ICU and critical care use, or favouring SIRS for better sensitivity. POC rapid-recognition technologies focus on vigilance, immediate therapy and ongoing reassessment. Biomolecular analytics, including microfluidics and smartphone technologies for sepsis biomarker detection, offer rapid, actionable information towards improved outcomes by enhancing patient risk stratification, accelerating treatment guidance, monitoring progression and evaluating response to treatment.

Without a gold standard for rapid detection of sepsis, and limitations in conventional diagnostic criteria and approaches, several advanced technologies offer reliability and accuracy. Molecular and biomarker-based assays (polymerase chain reaction [PCR] and next-generation sequencing [NGS]), enable rapid identification of bacterial and fungal pathogens directly from blood samples, reducing time to diagnosis. CRP, PCT, interleukins and lactate are used in single-analyte devices, aiding in rapid decision-making and treatment guidance, through their simplicity. Traditional biomarkers like PCT and CRP are supplemented by newer ones like interleukin-6, presepsin, host gene expression (SeptiCyte), host response (IntelliSep), monocyte distribution width (MDW) and immature granulocyte measurement (Qscout). These newer biomarkers offer improved sensitivity, specificity and workflow integration. Pathogen-focused tests like T2 panels complement early detection through quick confirmation of infectious agents.

Multiplex assays offer rapid detection, and artificial- or augmented-intelligence (AI)-driven predictive analytics and machine models can detect sepsis even before symptom onset and clinical recognition, predicting deterioration and reducing unnecessary antibiotic use. Real-world implementation at UC San Diego Health and Duke University Hospital shows reduced mortality rates (17% and 27%, respectively) and shorter hospital stays, using deep learning models.

POC testing enables enhanced clinical decision-making in emergency departments (EDs), ICUs and pre-hospital settings. In various settings, PCT-based diagnostics have proven utility, predictive value and performance. Procalcitonin’s emergence as a dominant, validated biomarker of bacterial burden in sepsis is evidenced through its diagnostic and prognostic impact.

PCT enables rapid discrimination between bacterial and viral infection (20 to 25 minutes), enabling risk stratification. PCT kinetics (half-life of 25 to 30 hours) enables improved management of critically ill patients by following PCT daily. When PCT drops to 80% of the peak value, antibiotics can be stopped. Shorter antibiotic duration minimises the potential to develop antibiotic resistance and overall leads to better outcomes. While lab-based PCT assays (QuidelOrtho, Roche, Abbott, bioMérieux, Beckman Coulter, Siemens) offer high precision and throughput, which are essential in hospital sepsis protocols, POC PCT is critical in EDs and ICUs. POC PCT is available through the speed and bedside convenience of microfluidics immunoassays testing (Quidel Triage). POC PCT is also available by fluorescence immunoassay technology (Finecare/Wondfo, Radiometer AQT90).

Use of early sepsis detection tools in all settings has a direct, profound impact on patient outcomes. Timely sepsis identification translates to initiating life-saving treatments earlier in the disease continuum, which sharply improves survival. Adoption of rapid detection tests by major health networks signals a growing demand for innovative diagnostics and creates a ripple effect of positive outcomes. Through a combination of clinical vigilance, POC diagnostics and evidence-based protocols, significant improvements in sepsis outcomes can be achieved. The integration of sepsis biomarkers, rapid tests and AI into medical workflows allows for rapid risk stratification and identification of sepsis. This comprehensive approach, coupled with rapid intervention, continuous monitoring, reassessment and enhanced antibiotic stewardship, results in shorter hospital stays, fewer complications and ultimately saves lives.