2835. Utilization of Clinical-Grade Metagenomics in Urinary Tract Infection Diagnostics: Improving High-Risk Patients’ Outcomes with a Genomic-Based Assay

BACKGROUND: Immunosuppressed patients and those experiencing complicated UTIs are more susceptible to misdiagnosis by outdated standard of care (SOC) diagnostics; resulting in ineffective treatment and risk of severe complications. Shotgun metagenomic sequencing can act as a highly accurate tool in profiling urogenital pathogens in high-risk patients. We assessed the performance of a genomic-based urine assay in patients where the SOC failed to identify pathogens and compiled clinical metadata from medical records to evaluate if antimicrobial stewardship could be improved. METHODS: Culture negative (no growth or < 100k CFU/mL) urine specimens (n=140) were collected from patients with pyuria and UTI symptoms then processed with the BIOTIA-ID Urine NGS Assay including DNA extraction, library preparation, Illumina NextSeq sequencing and analysis by BIOTIA-DX to identify urogenital pathogens. Findings were correlated with clinical metadata and administered antimicrobial therapies (Advarra Pro00038083, IRBNet 1950413-1). RESULTS: Our assay yielded an average of 2M microbial reads per sample with 98.6% passing laboratory QC. Microbial species were detected in 82.6% of the culture-negative specimens, of which 36.8% were single organisms and 45.6% were polymicrobial infections. Different pathogen profiles were distinguished based on prior antibiotic use, catheterization, or specific comorbidities (kidney transplant, cancer and prostatic hyperplasia). 50% of septic patients showed single organism infections, while cancer patients had higher incidence of polymicrobial infections (52%). Higher prevalence of fungal infections (20%) were observed in catheterized patients, and those with prior antibiotic therapy within 30 days. Retrospective evaluation revealed 63% prescribed antimicrobials would not target the organisms detected. Further, 57% of the cases could have potentially de-escalated their treatment. CONCLUSION: High-risk patients frequently harbor atypical pathogens leading to inaccurate SOC testing and ineffective therapeutics. Genomic-based diagnostics may improve accuracy of urogenital pathogen detection and offer physicians precision therapeutics with better health outcomes while enhancing antimicrobial stewardship. DISCLOSURES: Tiara Rivera, B.S., Biotia Inc.: Research Staff Sol Rey, BS, Biotia Inc: Researcher-Staff Xavier O. Jirau Serrano, MS, Biotia Inc: Research and development staff John C. Papciak, BS, Biotia Inc.: Staff Suraj S. Patel, n/a, Biotia Inc.: staff Bridget Harrison, B.A., Biotia Inc.: Clinical Program Manager- Staff Caitlin Otto, PhD, D(ABMM), Biotia Inc.: Staff Chris Mason, Ph.D., Biotia: Board Member|Biotia: Stocks/Bonds Heather L. Wells, MPH, PhD Candidate, Biotia, Inc.: Employee David C. Danko, Ph.D., Biotia Inc: Stocks/Bonds Niamh B. O'Hara, PhD, Biotia: Board Member|Biotia: 2 patents|Biotia: Ownership Interest|Biotia: Stocks/Bonds Mara Couto-Rodriguez, MS, Biotia Inc: Employee Dorottya Nagy-Szakal, MD PhD, Biotia Inc.: Employee|Biotia Inc.: Stocks/Bonds