Culture-independent detection systems for bloodstream infection

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.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.Peer-reviewed publications relevant to the topic have been searched through PubMed; manufacturers' websites have also been consulted as a data source.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.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.