B-114 Analytical characterization of a host-response test able to rapidly differentiate bacterial from viral infections developed for use on Beckman Coulter immunoassay analyzers

Abstract Background Antibiotic misuse is a key contributor to antimicrobial resistance. Difficulty in differentiating between bacterial and viral infections based on clinical presentation and standard lab values creates challenges in modifying prescribing behavior. MeMed BV is an FDA-cleared host-response test that can discriminate bacterial from viral infections with >99% negative predictive value (NPV). A numeric Bacterial versus Viral (BV) score is computationally generated by measuring the circulating levels of three host proteins. Shown below are the performance characteristics of Access MeMed BV, which Beckman Coulter is currently developing for use on its Access 2 and DxI 9000 analyzers. Methods Access MeMed BV consists of three distinct quantitative chemiluminescent sandwich immunoassays that measure the circulating levels of three host proteins: tumor necrosis factor-related apoptosis inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), or C-reactive protein (CRP) in a serum or Lithium Heparin (LiHep) plasma sample. These measurements generate a numeric BV score (0-100), with increasing score values indicating increased likelihood of bacterial infection. The time to first result is ∼22 min on the Access 2 analyzer and ∼15 min on the DxI 9000 analyzer. Analytical performance of the three constituent tests and/or the BV score, when appropriate, were assessed per CLSI guidelines for a range of attributes, including linearity, imprecision, sensitivity, sample type comparison (serum and LiHep plasma), and method comparison to an FDA-cleared MeMed BV test run on the MeMed Key analyzer. Characterization of these and other attributes are ongoing with preliminary results presented below. Results Each constituent assay demonstrated acceptable linearity across its analytical measuring range (AMR) (15-300 pg/mL for TRAIL, 100-2,000 pg/mL for IP-10, and 1-250 mg/L for CRP). Across multiple characterization studies, the reproducibility of the BV score (standard deviation) ranged from 0-3 score units, reflecting the low imprecision of the constituent assays. Each assay’s limit of quantitation (LoQ) (dose at 20% CV) was found to fall well below the bottom of its stated AMR. Passing-Bablok regression analysis of the BV scores measured in a total of 63 matched LiHep plasma and serum samples tested across two studies yielded a slope of 1.00 and intercept of -1. Finally, in a single characterization method comparison study, 104 native serum samples were measured using both Access MeMed BV and the MeMed Key MeMed BV test. The Passing-Bablok regression slope and intercept, respectively, were 0.97 and -2 pg/mL for TRAIL (N=96), 0.95 and 9 pg/mL for IP-10 (N=68), 1.01 and 1.5 mg/L for CRP (N=85), and 1.00 and 0 for the BV score (N=104). The Pearson’s correlation coefficient (r) was 0.99 for all three analytes and the BV score. Conclusion The Access MeMed BV test, currently in development for the Beckman Coulter Access 2 and DxI 9000 analyzers, demonstrates robust analytical performance and excellent agreement with the MeMed Key MeMed BV test. Once finalized, Access MeMed BV is expected to offer clinically actionable diagnostic information with a rapid turnaround time and seamless compatibility with existing laboratory workflows, showing significant promise as a valuable tool in improving the management and treatment of infections.