LAUSR

Management of urinary tract infections (UTIs) is highly variable and ∼50% of affected women may receive inappropriate antimicrobials. Precision Metagenomics-based detection of pathogens and antimicrobial resistance (AMR) markers can inform antimicrobial selection in support of stewardship practices. We investigated inter-physician agreement of culture and metagenomic results in a retrospective analysis. We used de-identified urine samples with results of urine culture & antimicrobial susceptibility testing (AST, n=25, 76% culture-positive) and the Explify® Urinary Pathogen ID/AMR Panel (UPIP, IDbyDNA Inc). UPIP is a Precision Metagenomics method to detect >170 uropathogens and >2,000 AMR markers. Four physicians reviewed culture/AST and UPIP results independently to assess if and how they would treat based on each set of results in a middle-aged, female patient with uncomplicated UTI (no comorbidities or medication allergies). Consensus was defined by simple majority; treatment decisions and antimicrobial choice were adjudicated by an infectious disease trained pharmacist. Inter-rater agreement (Fleiss’ kappa) and reliability for accurate case management (reference: adjudicator) were estimated for each method. Analytical agreement for uropathogen identification between the two methods was 72% with 95% positive agreement for common uropathogens. Consensus on whether or not to treat was reached for 96% (24/25) of cases for both culture/AST and UPIP; decisions were concordant between methods for 88% of cases (22/25). Inter-rater agreement was high (culture: k=0.73, UPIP: k=0.68; p< 0.05). Physicians were more likely to decide to treat based on culture results (17/25, 68%) than UPIP (15/25, 60%). UPIP detected additional organism(s) and/or AMR marker(s) compared with culture/AST alone that were informative for stewardship-guided treatment decisions in 28% (7/25) of samples. Figure 1: Physician Consensus Treatment Decisions Based on Results of Urine Sample Analysis by Precision Metagenomics or Urine Culture/AST Four infectious disease physicians independently reviewed paired results from analysis of a set of 25 clinical remnant urine samples by an investigational Precision Metagenomics method (UPIP) and by standard urine culture/AST and determined whether or not treatment would be warranted. Figure 2:Summary of Changes in Antimicrobial Selection based on Interpretation of Precision Metagenomics vs Culture/AST Results An infectious disease pharmacist reviewed and adjudicated hypothetical antimicrobial selections. All antimicrobial selections based on the results of the Precision Metagenomics method (UPIP) were found to be appropriate; in 7/15 cases, hypothetical treatment based on UPIP results would have resulted in a change in management that was evaluated to be consistent with stewardship practices. Physician agreement on hypothetical treatment recommendations was comparable between the investigational method (UPIP) and the reference method (urine culture/AST). In no case was there inappropriate consensus to treat based on UPIP results alone. The findings from this pilot analysis support the feasibility of metagenomics-guided management of UTIs. Benjamin Briggs, MD, PhD, CloudCath: Advisor/Consultant|CosmosID: Employee Benjamin Briggs, MD, PhD, CloudCath: Advisor/Consultant|CosmosID: Employee Robert Schlaberg, MD, MPH, IDBYDNA INC: Board Member|IDBYDNA INC: Explify-related IP|IDBYDNA INC: Employee|IDBYDNA INC: Stocks/Bonds.