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Background: Timely management of sepsis with early targeted antimicrobial therapy improves patient outcomes. Rapid molecular assays (RMAs) have emerged, enabling the detection of bloodstream infection (BSI) with a shorter turnaround time than blood cultures (BCs). The accuracy of several RMAs has not been comprehensively reviewed. We aimed to identify commercial RMAs reported in the literature and evaluate their diagnostic performance compared to BC. Methods: A systematic review and meta-analysis was conducted, covering MEDLINE, Cochrane Library, Embase, and Web of Science from inception to September 23, 2024. Eligible studies included patients with suspected or documented BSI, tested with both an RMA (turnaround time of ≤12 h, targeting ≥20 pathogens) and BC. Non-original research articles and animal studies were excluded. The primary outcomes were pooled sensitivity and specificity of RMAs for pathogen detection compared to BC. Bivariate analysis was used to produce summary receiver operating characteristic plots and diagnostic metric measures stratified by different units of analysis (sample versus patient), RMA types, and patient populations. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and Quality Assessment of Diagnostic Accuracy Studies-Comparative (QUADAS-C) tools. The study was registered with PROSPERO, CRD42022377280. Findings: A total of 63,916 articles were identified, of which 104 were included in the qualitative synthesis and 75 in the quantitative synthesis, covering 17,952 samples and 11,393 patients analyzed separately. Eleven RMAs were identified, with four included in the RMA-based subgroup analysis (LightCycler SeptiFast Test MGRADE®, IRIDICA BAC BSI assay, SepsiTest, MagicPlex Sepsis Test) and five additional ones in the pooled analysis (UMD-SelectNA, VYOO®, MicrobScan assay, MicrobScan-Kairos24/7, REBA Sepsis-ID test). Two RMAs were included in the qualitative synthesis only (InfectID-BSI, Pilot Gene Technology droplet digital polymerase chain reaction). Pooled specificity of RMAs was higher (0.858, 95% confidence interval (CI) 0.830-0.883) than sensitivity (0.659, 95% CI 0.594-0.719) by patient. Sensitivities varied by RMA type from 0.492 (95% CI 0.390-0.594, MagicPlex Sepsis Test) to 0.783 (95% CI 0.662-0.870, IRIDICA BAC BSI assay) by patient. Specificities varied more by patient population, ranging from 0.811 (95% CI 0.716-0.879) in the intensive care population to 0.892 (95% CI 0.838-0.930) in the emergency department population, by patient. Similar metrics were observed when the analysis was done by sample. Risk of bias was judged to be high in all included articles. Interpretation: Despite their shorter turnaround time, low sensitivity means RMAs cannot replace BCs. However, our data indicate that RMAs may have value as an add-on test by increasing pathogen detection rates. Higher-sensitivity RMAs are needed which could possibly be achieved by expanding pathogen coverage and increasing blood sample volumes. High-quality implementation studies and standardized reporting are required to assess the clinical advantages of RMAs. Funding: Centre for Translational Medicine, Semmelweis University.
Rapszky et al. (Wed,) studied this question.