Urine Gene Analysis Compared to Urine Culture for Pathogen Detection

INTRODUCTION: Urine testing by DNA next-generation sequencing (NGS) PCR for pathogen detection, quantification, and resistance gene identification produces faster and more precise results in monomicrobial and polymicrobial urinary tract infections (UTI) than conventional laboratory urine culture techniques. OBJECTIVE: The objective of this study is to evaluate the impact of utilizing a syndromic PCR panel for the management of patients suspected to have urinary tract infections. METHODS: This was a prospective observational study of ambulatory women ≥60 years of age presenting with symptoms of an acute UTI. For all patients, urine culture and NGS (using the technology platform ABXAssistTM) were collected. Urine cultures were completed at the medical center laboratory while PCR testing was transported via mail to a lab at Vikor Scientific. The results were transmitted to the treating physician portal when they were available. Treatment recommendation for the UTI was at the provider’s discretion and part of the patient’s clinical care; initial treatment was based on the results of the first available result, culture or NGS. Treatment changes were made if there were discrepancies between test modalities, if the change would lead to increased microbial change. Patients requiring chronic catheterization, urinary diversion antibiotic therapy for any reason, or a UTI within 21 days of presentation were excluded. Baseline demographics and treatment information within 30 days were collected. Patients completed baseline UTI-SIQ-8 and the UTI Symptom Assessment questionnaires, which were completed again 30 days after enrollment. RESULTS: A total of 94 patients were enrolled in the study. Those with positive urine cultures (N=40) and negative urine cultures (N=54) did not differ statistically in baseline characteristics. Of the patients with positive urine cultures, 97.5% had positive NGS, while 75.9% (N=41) of those with negative urine cultures also had positive NGS, all of whom were prescribed antibiotic therapy based on NGS results. N=41 of those with negative urine cultures also had positive gene analysis, all of whom were prescribed antibiotic therapy based on gene analysis results. For positive cultures, there was fair to substantial agreement for pathogen type: Cohen’s kappa for E. coli (κ=0.63), enterococci (κ=0.22), Enterobacteriaceae (κ=0.47), Klebsiella sp. (κ=0.54), and Proteus mirabilis (κ=0.47). Patients with a positive urine culture had a shorter optimal time to treatment than those who had a negative urine culture followed by a positive NGS result (68.3 hours vs 91.2 hours, p=0.01). However, patients with both with culture-directed treatment and negative urine cultures and NGS-directed treatment reported a similar rate of improvement in their symptoms (72.2% for culture negative vs 72.5% for culture positive) (p=0.54). CONCLUSIONS: NGS may be an effective method of identifying urinary pathogens in symptomatic patients, particularly those with negative urine cultures (Tables 1 and 2).