Diagnosing and Managing Sepsis by Probing the Host Response to Infection: Advances, Opportunities, and Challenges

Abstract

Sepsis is a major source of mortality and morbidity globally. Accurately diagnosing sepsis remains challenging due to the heterogeneous nature of the disease, and delays in diagnosis and intervention contribute to high mortality rates. Measuring the host response to infection enables more rapid diagnosis of sepsis than is possible through direct detection of the causative pathogen, and recent advances in host response diagnostics and prognostics hold promise for improving outcomes. The current review discusses recent advances in the technologies used to probe the host response to infection, particularly those based on transcriptomics. These are discussed in the context of contemporary approaches to diagnosing and prognosing sepsis, and recommendations are made for successful development and validation of host response technologies.

Update on diagnosis and management of sepsis in cirrhosis: Current advances

“…Jalan and colleagues studied the prognostic value of the PIRO model on outcomes in patients with ACLF. The authors found that in patients with organ failures, previous hospitalization (predisposition), persistence and severity of inflammation (response), and severity of organ failure (organ dysfunction) were associated with higher mortality[ 8 , 9 ]. Maiwall et al[ 10 ] in a prospective study of ACLF patients showed that serum creatinine, bilirubin, potassium, and blood urea at baseline (predisposition); nephrotoxic medications (insult); SIRS (response), and circulatory failure (organ dysfunction) identified those at risk of developing acute kidney injury during the disease course and death.…”

Diagnosis of bacterial sepsis: why are tests for bacteremia not sufficient?

“…Both the Surviving Sepsis Campaign guidelines and the CMS 1 h 'SEP-1ʹ bundle can almost entirely be reduced to two main treatments: (1) source control and antimicrobial therapy to fight an underlying infection, and (2) supportive care to maintain physiology [8]. In general, the diagnostic components can also be split into two separate but complementary axes, namely: (1) whether there is an infection, and (2) how severe the underlying condition is [9,10]. Other than lactate, almost all in vitro diagnostics for sepsis primarily lead to clinical actions regarding whether and how to properly attain source control and treat with antimicrobials.…”

“…This is particularly true in pediatric patients where the volume of blood that can be obtained is limited. The immune system can potentially inform both whether an infection is present, and broadly what type (bacterial, viral, or fungal), but also can estimate the risk of sepsis and/or death [10]. Further, given their high abundance, host-response-based biomarkers can be measured in minutes.…”

“…However, the most accurate of these, procalcitonin, may be useful as a longitudinal marker to determine antibiotic efficacy [27], potentially even reducing overall mortality [28]. However, it may not be accurate enough to impact physician prescribing behavior (at least without the addition of a robust stewardship program) [10,29]. More recently, revived focus has been put on host-response multi-marker diagnostics, in particular, novel host immune mRNA panels [30][31][32][33].…”

Empiric Antibiotic Prescribing for Suspected Sepsis: A Stewardship Balancing Act

“…While the opportunity to tailor antibiotic therapy based on culture and susceptibility results is not traditionally available to ED clinicians, this paradigm is rapidly changing as emerging biomarker, host immune gene expression and microbiology-based point-of-care technologies continue to improve the accuracy of sepsis diagnosis and reduce the time to pathogen identification. 17,18 Once validated and disseminated, these novel technologies will help to differentiate true sepsis from mimics and facilitate optimal empiric antibiotic selection and early de-escalation so that the use of broad-spectrum agents can be minimized.…”