2835. Utilization of Clinical-Grade Metagenomics in Urinary Tract Infection Diagnostics: Improving High-Risk Patients’ Outcomes with a Genomic-Based Assay
Authors: Romero Eduardo J Morfa , Augenbraun Michael , Rivera Tiara , Rey Sol , Serrano Xavier O Jirau , Papciak John C , Patel Suraj S , Harrison Bridget , Plourde Anna , Otto Caitlin , Mason Chris , Wells Heather L , Danko David C , O’Hara Niamh B , Couto-Rodriguez Mara , Nagy-Szakal Dorottya 
Published: November 2023

Abstract

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Immunosuppressed patients and those experiencing complicated UTIs are more susceptible to misdiagnosis by outdated standard of care (SOC) diagnostics; resulting in ineffective treatment and risk of severe complications.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 &lt; 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