Preventing, spotting, treating and beating sepsis in 2022

The symposium “Sepsis 2022: prevent it, spot it, treat it, beat it” at ECCMID 2022, organized by the ISF (International Sepsis Forum) and the ESGBIES (ESCMID Study Group for Bloodstream Infections, and Endocarditis and Sepsis), covered a variety of areas in sepsis management — from pathophysiology and diagnostics to long-term consequences and future improvements.

Sepsis and innate immunity

Both animal models and translational studies have highlighted a major role for innate immunity in sepsis pathophysiology and prognosis. System-wide dysregulation in sepsis involves too many factors to be encompassed by single measurements. Omics approaches allow definition of patient groups with distinct expression profiles. However, the sepsis endotypes need to be standardized since the involvement of innate cells in sepsis vary between patients depending on the source of infection, and possibly based on the patient’s ethnicity, age, and co-morbidities (Peters-Sengers et al., 2022). Furthermore, for technologies to be usable in clinical practice, there is a need for easy and fast access. 

Ultimately, these techniques could be used for tailored treatment of endotype-driven combination therapy consisting of 1) antibiotics limiting the infection, 2) damage control therapy limiting the overactivation of innate response, and 3) reprogramming of cells by cell therapy and 4) possibly by epigenetic or metabolic modulation.

What is hot in sepsis diagnostics?

Both time and choice of antibiotic treatment in sepsis are critical for patient outcome. However, there are several limitations in sepsis diagnostics by conventional methods, such as the time to positivity and the 30–50% sensitivity of blood cultures. Thus, accurate and rapid microbiological diagnostics, particularly antimicrobial susceptibility testing, are needed.

The first class of rapid diagnostic tests are culture independent tests that are fast but costly, unable to test for antimicrobial susceptibility, and may give inaccurate interpretation. The second class are tests performed on positive blood cultures that enable more rapid pathogen identification and detection of resistant genes than conventional methods. However, they can have limited panel size, reduced quality of detecting polymicrobial cultures, and require concurrent conventional identification and susceptibility testing. 

The choice of the most appropriate techniques should be based on local epidemiology and on specific patient populations and antibiotic prescription habits. Overall, rapid microbiological diagnostics implemented together with antimicrobial stewardship can facilitate faster antibiotic modifications during sepsis and aid clinicians in providing timely and effective therapy, while supporting antimicrobial stewardship efforts.

Long-term consequences of sepsis

Sepsis survivors survive with residual morbidity, such as physical, cognitive, or cardiovascular disability. However, at least 88% of sepsis survivors are discharged to their usual residence in the UK (Shankar-Hari et al., 2019). Studies have shown that rehospitalization occurs often among these patients (Shankar-Hari et al., ICM 2020). The most common reasons for rehospitalization are a new sepsis or other infection, poorly managed co-morbidity, or organ failure (Prescott et al., 2015). Rehospitalization has been shown to increase the risk of death roughly 6–10 times, and thus many deaths among sepsis patients are predictable (Shankar-Hari et al., JAMA Netw Open. 2020). For this reason, there are tools (such as that can predict this risk and change the way these patients are looked after.

ECCMID 2022 references:

Sepsis and innate immunity. Luc de Chaisemartin (Paris, France). Presented at ECCMID 2022 on 25 April 2022. 

What is hot in sepsis diagnostics? Alessandra Bandera (Milan, Italy). Presented at ECCMID 2022 on 25 April 2022. 

Long-term consequences of sepsis. Manu Shankar Hari (Edinburgh, UK). Presented at ECCMID 2022 on 25 April 2022. 

Beyond antibiotics: improving care of patients with BSI and sepsis. Jordi Rello (Barcelona, Spain). Presented at ECCMID 2022 on 25 April 2022. 

Additional references: 

Peters-Sengers H, Butler JM, Uhel F, et al. Source-specific host response and outcomes in critically ill patients with sepsis: a prospective cohort study. Intensive Care Med. 2022 Jan;48(1):92-102. doi: 10.1007/s00134-021-06574-0. 

Prescott HC, Langa KM, Iwashyna TJ. Readmission Diagnoses After Hospitalization for Severe Sepsis and Other Acute Medical Conditions. JAMA. 2015;313(10):1055–1057. doi:10.1001/jama.2015.1410

Shankar-Hari M, Harrison DA, Ferrando-Vivas P, et al. Risk Factors at Index Hospitalization Associated With Longer-term Mortality in Adult Sepsis Survivors. JAMA Netw Open. 2019 May 3;2(5):e194900. doi: 10.1001/jamanetworkopen.2019.4900. 

Shankar-Hari M, Saha R, Wilson J, et al. Rate and risk factors for rehospitalisation in sepsis survivors: systematic review and meta-analysis. Intensive Care Med. 2020 Apr;46(4):619-636. doi: 10.1007/s00134-019-05908-3. 

Shankar-Hari M, Rubenfeld GD, Ferrando-Vivas P, et al. Development, Validation, and Clinical Utility Assessment of a Prognostic Score for 1-Year Unplanned Rehospitalization or Death of Adult Sepsis Survivors. JAMA Netw Open. 2020 Sep 1;3(9):e2013580. doi: 10.1001/jamanetworkopen.2020.13580.