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... Show moreObjectives: 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 inflam- matory 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. Manu P. Bilsen, Clin Microbiol Infect 2024;30:216 (c) 2023 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). Show less
Aim of this thesis was to provide evidence for the clinical implication of biomarkers in blood and urine, as well as genetic markers, for the prediction of the severity and course of febrile UTI.... Show moreAim of this thesis was to provide evidence for the clinical implication of biomarkers in blood and urine, as well as genetic markers, for the prediction of the severity and course of febrile UTI. Furthermore, this thesis focused on optimization of antimicrobial treatment of febrile UTI. The main results are: 1. Recent hospitalization, indwelling urinary catheter and especially individual fluoroquinolone (FQ) use are independent risk factors for a FQ-resistant Escherichia coli febrile UTI. 2. Women with febrile UTI, including postmenopausal women and those with comorbidities, can be safely and successfully treated with a 7-day course of oral ciprofloxacin. In men, however, treatment duration should be at least 14 days. 3. Diabetes mellitus does not affect the clinical presentation and course of febrile UTI; concurrent illnesses and higher age of the diabetic population attribute to a more complicated course. 4. MR-proADM more accurately predicts a complicated course of disease than currently available inflammatory biomarkers. Importantly, biomarkers derived directly from host defense mechanisms are not suitable to distinguish between febrile UTI patients with and without bacteremia. 5. MP-TF activity is related to disease severity and bacteraemia in febrile E. coli UTI and may contribute to the prothrombotic state in gram-negative sepsis. Show less
