Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

UTI Biomarkers in Symptomatic Patients are Significantly Elevated at Microbial Densities of 10,000 cells or CFUs per mL Indicating a Lower Microbial Density Threshold for Diagnosing UTIs

Version 1 : Received: 29 June 2023 / Approved: 30 June 2023 / Online: 3 July 2023 (09:28:56 CEST)

A peer-reviewed article of this Preprint also exists.

Parnell, L.K.S.; Luke, N.; Mathur, M.; Festa, R.A.; Haley, E.; Wang, J.; Jiang, Y.; Anderson, L.; Baunoch, D. Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs. Diagnostics 2023, 13, 2688. Parnell, L.K.S.; Luke, N.; Mathur, M.; Festa, R.A.; Haley, E.; Wang, J.; Jiang, Y.; Anderson, L.; Baunoch, D. Elevated UTI Biomarkers in Symptomatic Patients with Urine Microbial Densities of 10,000 CFU/mL Indicate a Lower Threshold for Diagnosing UTIs. Diagnostics 2023, 13, 2688.

Abstract

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic presumptive UTI patients and correlated them with detected levels of immune response biomarkers NGAL, IL-8, and IL-1β. The objective was to identify changes in immune response at different microbial densities and determine an optimal threshold for diagnosing symptomatic UTIs. Midstream clean-catch urine samples were analyzed for microbial identification and quantification using SUC and M-PCR, while NGAL, IL-8, and IL-1β levels were measured with ELISA. NGAL, IL-8, and IL-1β levels were all significantly higher in symptomatic subjects with microbial densities ≥ 10,000 cells/mL by M-PCR (p < 0.0069) or equivalent CFUs/mL by SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥ 10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable for diagnosing UTIs. These findings challenge the widely used threshold of 100,000 CFU per mL, which may overlook many active UTI cases.

Keywords

urinary tract infection (UTI); standard urine culture (SUC); multiplex polymerase chain reaction (M-PCR); urine biomarkers; diagnostic testing; neutrophil gelatinase-associated lipocalin (NGAL); interleukin (IL)-8, IL-1β

Subject

Medicine and Pharmacology, Urology and Nephrology

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