Culture-independent detection systems for bloodstream infection
Peri AM, Harris PNA, Paterson DL. Clin Microbiol Infect 2022;28(2):195–201
Background: Sepsis and bloodstream infection are associated with significant morbidity and mortality, and early effective antimicrobial therapy has been demonstrated to improve patient outcomes. Traditional culture-based methods, however, have several limitations that hamper a prompt diagnosis in bloodstream infection, including long turnaround times and limited sensitivity. In recent years, advances have been made in the development of several technologies that allow the identification of pathogens and their resistance markers directly from whole blood, possibly representing promising alternatives to conventional culture-based methods.
Objectives: To review the currently commercially available emerging assays for the diagnosis of bloodstream infections directly from whole blood, including their performance and the available data about their impact on patient outcome.
Sources: Peer-reviewed publications relevant to the topic have been searched through PubMed; manufacturers’ websites have also been consulted as a data source.
Content: We have reviewed available data about the following technologies: multiplex real-time PCR working directly from whole blood (Magicplex Sepsis Real-Time test, Seegene), PCR combined with T2 Magnetic Resonance (T2Candida and T2Bacteria panel, T2Biosystem), and metagenomics-based assays (including SepsiTest, Molzym; iDTECT Dx Blood, PathoQuest; Karius NGS plasma Test, Karius). Performance characteristics, advantages and pitfalls of each method are described, and available data about their impact on patients’ clinical outcomes are discussed.
Implications: The potential of rapid diagnostic tests applied on whole blood for improving the management of patients with bloodstream infection and sepsis is high, both in terms of reducing turnaround times and improving the sensitivity of pathogen and antimicrobial resistance detection. However, overall, there is still a scarcity of data about the real-life performance of such tests, and well-designed studies are awaited for assessing the impact of these emerging technologies on patient outcomes.
Sepsis and the microcirculation: the impact on outcomes
Yajnik V, Maarouf R. Curr Opin Anaesthesiol 2022;35(2):230–235
Purpose of review: Advances in the treatment of septic shock have historically focused on resuscitation endpoints, mainly mean arterial pressure and cardiac output. As the definitions of sepsis and septic
shock have shifted to focus on the diversity of causes of dysregulated host-response we have seen an emerging phenotype where tissue hypoxia persists despite adequate macrocirculatory parameters. Interest in the topic of microcirculation is re-emerging as validated bedside techniques for hemodynamic monitoring, such as video microscopes, are becoming available. We review the current understanding of how sepsis induced hypoperfusion with a focus on recent advances in monitoring the microcirculation, and how a proliferation of biomarkers and emerging therapeutic targets may impact future research.
Recent findings: Conventional hemodynamic monitoring systems fail to assess the microcirculation, and it’s response to treatment. Lactate and venous oxygen saturations often drive biomarkerguided sepsis management. Visual assessments such as mottling and capillary refill time are often associated with predicting outcomes, but sometimes can have issues with inter-provider reliability. Microcirculatory damage can be observed sublingually and appears to have prognostic value.
Summary: Sepsis is associated with changes in the microcirculation that can lead to tissue hypoxia and organ dysfunction. Further
studies are needed to validate the usefulness of microcirculatory bedside tools in guiding resuscitative efforts.
Molecular methodologies for improved polymicrobial sepsis diagnosis
Doualeh M, Payne M, Litton E et al. Int J Mol Sci 2022;23(9):4484
Polymicrobial sepsis is associated with worse patient outcomes than monomicrobial sepsis. Routinely used culture-dependent microbiological diagnostic techniques have low sensitivity, often leading to missed identification of all causative organisms. To overcome these limitations, culture-independent methods incorporating advanced molecular technologies have recently been explored. However, contamination, assay inhibition and interference from host DNA are issues that must be addressed before these methods can be relied on for routine clinical use.
While the host component of the complex sepsis host-pathogen interplay is well described, less is known about the pathogen’s role, including pathogen-pathogen interactions in polymicrobial sepsis. This review highlights the clinical significance of polymicrobial sepsis and addresses how promising alternative molecular microbiology methods can be improved to detect polymicrobial infections. It also discusses how the application of shotgun metagenomics can be used to uncover pathogen/pathogen interactions in polymicrobial sepsis cases and their potential role in the clinical course of this condition.
Diagnosis of sepsis with inflammatory biomarkers, cytokines, endothelial functional markers from SIRS patients
Xue M, Xu F, Yang Y et al.
Medicine (Baltimore) 2022; 101(7):e28681
Background: Sepsis is a life-threatening illness with a challenging diagnosis. Rapid detection is the key to successful treatment of sepsis. To investigate diagnostic value, the plasma protein profiles of inflammatory biomarkers, cytokines, and endothelial functional markers were compared between healthy controls, SIRS, and septic patients.
Methods: The plasma protein profiles were performed by Luminex Assay in a cohort of 50 SIRS patients, 82 septic patients and 25 healthy controls. Fourteen plasma proteins were analyzed in the same cohort: IL-1β, IL-6, IL-8, IL-10, CCL-2, VEGF, VEGF-C, VEGFR2, CD62E, CD62P, MFG-E8, ICAM-1, TFPI, Urokinase.
Result: IL-2R, IL-6, IL-8, IL-10, CCL-2, ICAM-1, and urokinase were significantly higher in sepsis patients than SIRS patients. VEGF, IL-1β, CD62E, CD62P, MFG-E8, and TFPI have no statistical difference. VEGF-C, VEGFR2 were significantly different in SIRS patients than sepsis patients. Urokinase, ICAM-1, and VEGFR2 were significantly different between sepsis group and SIRS group. The AUCs of urokinase, ICAM-1, and VEGFR2 and the combination for the diag-
nosis of sepsis were 0.650, 0.688, 0.643, and 0.741, respectively.
Conclusions: Most patients have the higher level of several cytokines and developed endothelial cell injury in the initial phase of sepsis, urokinase, ICAM-1, and VEGFR2 may be useful to evaluate severity and prognosis of sepsis patients.