Diagnostic accuracy of urine biomarkers for urinary tract infection in older women: a case-control study

Manu P Bilsen; Maxim M Treep; Margaretha J Aantjes; Esther van Andel; Janneke E Stalenhoef; Cees van Nieuwkoop; Eliane M S Leyten; Nathalie M Delfos; Janneke I M van Uhm; Martijn Sijbom; Abimbola A Akintola; Mattijs E Numans; Wilco P Achterberg; Simon P Mooijaart; Martha T van der Beek; Christa M Cobbaert; Simon P Conroy; Leo G Visser; Merel M C Lambregts

doi:10.1016/j.cmi.2023.09.023

Diagnostic accuracy of urine biomarkers for urinary tract infection in older women: a case-control study

Clin Microbiol Infect. 2024 Feb;30(2):216-222. doi: 10.1016/j.cmi.2023.09.023. Epub 2023 Oct 5.

Authors

Manu P Bilsen¹, Maxim M Treep², Margaretha J Aantjes³, Esther van Andel², Janneke E Stalenhoef⁴, Cees van Nieuwkoop⁵, Eliane M S Leyten⁶, Nathalie M Delfos⁷, Janneke I M van Uhm⁸, Martijn Sijbom⁹, Abimbola A Akintola⁹, Mattijs E Numans⁹, Wilco P Achterberg¹⁰, Simon P Mooijaart¹¹, Martha T van der Beek¹², Christa M Cobbaert², Simon P Conroy¹³, Leo G Visser³, Merel M C Lambregts³

Affiliations

¹ Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.p.bilsen@lumc.nl.
² Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
³ Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Internal Medicine, OVLG, Amsterdam, The Netherlands.
⁵ Department of Internal Medicine, Haga Teaching Hospital, The Hague, The Netherlands; Department of Public Health and Primary Care, Leiden University Medical Center, Health Campus The Hague, The Netherlands.
⁶ Department of Internal Medicine, Haaglanden Medisch Centrum, The Hague, The Netherlands.
⁷ Department of Internal Medicine, Alrijne Hospital, Leiderdorp, The Netherlands.
⁸ Department of Urology, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Department of Public Health and Primary Care, Leiden University Medical Center, Health Campus The Hague, The Netherlands.
¹⁰ Department of Public Health and Primary Care, Leiden University Medical Center, Health Campus The Hague, The Netherlands; LUMC Center for Medicine for Older People, Leiden University Medical Center, Leiden, The Netherlands.
¹¹ LUMC Center for Medicine for Older People, Leiden University Medical Center, Leiden, The Netherlands; Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
¹² Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
¹³ Medical Research Council Unit for Lifelong Health and Ageing at University College London, University College London, London, United Kingdom.

PMID: 37805035
DOI: 10.1016/j.cmi.2023.09.023

Abstract

Objectives: Urinary tract infection (UTI) is common among older women. However, diagnosis is challenging because of frequent chronic lower urinary tract symptoms, cognitive impairment, and a high prevalence of asymptomatic bacteriuria (ASB). Current urine diagnostics lack specificity, leading to unnecessary treatment and antimicrobial resistance. This study aimed to evaluate the diagnostic accuracy of 12 urine biomarkers for diagnosing UTI in older women.

Methods: In this case-control study, cases were women ≥65 years with ≥2 new-onset lower urinary tract symptoms, pyuria, and one uropathogen ≥10⁴ CFU/mL. Controls were asymptomatic and classified as ASB (one uropathogen ≥10⁵ CFU/mL), negative culture, or mixed flora. Urine biomarker concentrations were measured through liquid chromatography-mass spectrometry and ELISA. Diagnostic accuracy parameters of individual biomarkers and a biomarker model were derived from receiver operating characteristic curves.

Results: We included 162 community-dwelling and institutionalized older women. Five urine inflammatory biomarkers demonstrated high discriminative ability (area under the curve ≥0.80): interleukin 6, azurocidin, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinases 2, and C-X-C motif chemokine 9. Azurocidin exhibited the highest diagnostic accuracy (sensitivity 86% [95% CI 75%-93%] and specificity 89% [95% CI 82%-94%] at 16.7 ng/mmol creatinine). A combined biomarker and pyuria model showed improved diagnostic accuracy in patients with UTI and ASB, compared with pyuria alone.

Discussion: We identified several urine biomarkers that accurately differentiated older women with UTI from asymptomatic women, including ASB. These findings represent a potential advancement towards improved diagnostics for UTI in older women and warrant validation in a diverse population.

Keywords: Antimicrobial stewardship; Asymptomatic bacteriuria; Biomarkers; Diagnostic accuracy; Older patients; Urinary tract infection.

MeSH terms

Aged
Bacteriuria* / drug therapy
Biomarkers
Case-Control Studies
Female
Humans
Lower Urinary Tract Symptoms*
Male
Pyuria* / diagnosis
Urinary Tract Infections* / drug therapy

Substances

Biomarkers