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Abstract Background Bloodstream infection (BSI) is a serious and life-threatening condition requiring timely diagnosis and treatment. This study evaluated a multi-target molecular assay under development for rapid and accurate identification of gram-positive (GP) bacteria directly from blood culture specimens. Here, we report progress in developing a multiplexed gram-positive blood culture assay in development to identify 13 pathogens and 3 resistance markers in approximately 2 hours. Methods The assay was performed directly on blood culture positive specimens determined to contain a GP organism. A 300 µL aliquot was processed in a single-use cartridge, utilizing a sensitive hybridization-based assay for rapid, direct detection without the need for target amplification. This fully automated system performs nucleic acid extraction followed by hybridization to a microarray with capture probes specifically designed to detect the clinically relevant gram-positive bacteria and resistance genes via gold nanoparticle chemistry with silver-enhanced signal amplification. Results The prototype assay demonstrated 100% positivity for GP targets and 0% for negative blood cultures in a growth and detection study from ring positive bottles and bottles grown up to 8 hours past ring positivity. Over 1,500 samples were tested as part of a site-to-site reproducibility study including 16 blood culture samples comprised of 7 on-panel organisms, one off-panel organism, and one negative across 3 sites resulting in 99.7% assay reproducibility. It accurately detected all targets, including resistance markers, across 13 media types and demonstrated 100% inclusivity for 183 on-panel strains, including resistance markers. The prototype assay maintained sensitivity even with low concentrations of on-panel GP organisms in the presence of high levels of other co-infecting GP or gram-negative bacteria. Clinical validation is underway with over 600 prospective samples, supporting the ongoing assessment of the assay's real-world performance. Conclusion This rapid, highly sensitive prototype assay accurately detects GP pathogens and resistance markers, supporting timely BSI management directly from positive blood culture samples and without target amplification. Disclosures Christine Pepich, BS, Diasorin: Employee Samantha Coons, BS, DiaSorin: Employee Seema Shaikh, MS, Diasorin: Employee Brian Bernier, PhD, Diasorin: Employee Amanda Seyfert, MS, Diasorin: Employee Janet Farhang, PhD, Diasorin: Employee|Diasorin: Employee Sundaresh Brahmasandra, PhD, Diasorin: Employee
Published in: Open Forum Infectious Diseases
Volume 13, Issue Supplement_1