Getting Up to Speed: Rapid Pathogen and Antimicrobial Resistance Diagnostics in Sepsis

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Time to receive effective therapy is a primary determinant of mortality in patients with sepsis. Blood culture is the reference standard for the microbiological diagnosis of bloodstream infections, despite its low sensitivity and prolonged time to receive a pathogen detection. In recent years, rapid tests for pathogen identification, antimicrobial susceptibility, and sepsis identification have emerged, both culture-based and culture-independent methods. This rapid narrative review presents currently commercially available approved diagnostic molecular technologies in bloodstream infections, including their clinical performance and impact on patient outcome, when available. Peer-reviewed publications relevant to the topic were searched through PubMed, and manufacturer websites of commercially available assays identified were also consulted as further sources of information. We have reviewed data about the following technologies for pathogen identification: fluorescence in situ hybridization with peptide nucleic acid probes (Accelerate Pheno^TM), microarray-based assay (Verigene^®), multiplex polymerase chain reaction (cobas^® eplex, BioFire^® FilmArray^®, Molecular Mouse, Unyvero BCU System^TM), matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (Rapid MBT Sepsityper^®), T2 magnetic resonance (T2Bacteria Panel), and metagenomics-based assays (Karius^©, DISQVER^®, Day Zero Diagnostics). Technologies for antimicrobial susceptibility testing included the following: Alfed 60 AST^TM, VITEK^® REVEAL^TM, dRAST^TM, ASTar^®, Fastinov^®, QuickMIC^®, Resistell^TM, and LifeScale. Characteristics, microbiological performance, and issues of each method are described, as well as their clinical performance, when available.

Keywords: antimicrobial resistance; bloodstream infection; pathogen diagnosis; rapid diagnostics; sepsis diagnosis.

Figure 1

Time to receive results of selected rapid diagnostic tests in sepsis. Abbreviations: ID—identification; MALDI-TOF MS—matrix-assisted laser desorption-ionization time-of-flight mass spectrometry; PNA-FISH—fluorescence in situ hybridization with peptide nucleic acid probes; PCR—polymerase chain reaction; AST—antimicrobial susceptibility testing; BC+—blood culture positivity. Day zero diagnostics does not specify how many hours are needed for results.