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Development of gender-specific thresholds in urine flow cytometry testing for urinary tract infection

Background

A urinary tract infection (UTI) is an infection – usually bacterial – of any part of the urinary tract. Most commonly, a UTI would involve the lower urinary tract (urethra and bladder), and non-complicated lower UTIs are more common in women. Mild UTIs can resolve naturally, and pain killers, application of heat to the abdomen and good hydration can aid the symptoms. More persistent or serious UTIs are treated with antibiotics.

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Diagnosis

Diagnosis of a non-complicated lower UTI involves presence of clinical signs and symptoms, such as dysuria, new noctiuria (and increased frequency of urination generally) and cloudy urine that may be also show the presence of blood. Two or more of these symptoms would be enough to conclude that a UTI is likely without any further testing. In the presence of only one symptom, diagnosis can be aided by urinalysis with a dipstick to check for the presence of nitrite, leukocytes and red blood cells, as well as with urine culture to confirm the presence of infection and to determine antibiotic susceptibility.

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Urine dipstick tests give good results in younger patients but are less reliable for older adults (Adobe Stock)

Challenges to diagnosis

This protocol works well for younger people. However, in older people, the symptoms can be more non-specific and cognitive capacity can be reduced, which puts an emphasis on the results of urinalaysis dipstick tests and urine culture. Unfortunately, the increased presence of asymptomatic bacteriuria in older adults is a confounding factor for urine culture results, which then demonstrate the presence of bacteria but are not indicative of a UTI. Additionally, urine dipsticks are not as reliable for the identification of UTIs in older adults, again because of the prevalence of confounding asymptomatic bacteriuria, but also because the leukocyturia thresholds used to guide the diagnosis of UTIs are based on younger populations and may not be appropriate for older people. These factors therefore result in an overdiagnosis of UTI in older people, with a concomitant overtreatment with antibiotics, which results in an increased risk of antibiotic resistance.

Analysis of UTI in older adults by flow cytometry

In their recent paper, Biguenet et al. evaluated the use of flow cytometry to establish if this method could give an accurate indication of a UTI diagnosis in older patients without having to wait for urine culture results [1]. After careful review, 69 patients were determined to meet the eligibility criteria for UTI and 387 patients without UTI were included as controls. The patients were all aged 65 years or older and had been admitted to the emergency department of the Besançon University Hospital (Besançon, France) over a 6-month period. Clinical data including the presence or absence of major symptoms (dysuria and pollakiuria), minor symptoms (fever/chills, confusion, hypotension, flank pain, urological obstruction), as well as onset of incontinence, acute renal insufficiency, acute urinary retention were recorded. Urine dipstick results were obtained before collection of biological parameters and urinalysis using the UF-4000 (Sysmex), and urine culture. The biological measurements included analysis of concentrations of C-reactive protein, blood leukocytes, urinary red blood cells, urinary leukocytes, bacteria and other cells. Statistical analysis of their findings showed that, in combination, bacteriuria and leukocyturia were strongly associated with UTI, with thresholds of 150 bacteria/μL and 50 leukocytes/μL (both negative likelihood ratio (LR- <0.1). Urine dipsticks effectively excluded UTI in men (LR- <0.1) but were less reliable in women (LR- = 0.129). In conclusion, the authors provide gender-specific diagnostic algorithms, saying that urine flow cytometry provides valuable diagnostic thresholds for bacteriuria and leukocyturia and helps to exclude UTI before culture results and recommend that the diagnosis of UTI in older patients should take into account gender differences.

These findings are limited by the small size of the patient cohort but, following confirmation in larger studies, the algorithms described could provide a useful approach for a faster exclusion of UTI in older adults, particularly older women.

 Reference
1. Biguenet A, Champy E, Gilis M, Gbaguidi-Haore H, Patry I, Bouiller K, Bertrand X. Urine flow cytometry in older adults urinary tract infection diagnosis: is it time to reevaluate thresholds for men and women? BMC Geriatr 2025;25(1):417 (https://doi.org/10.1186/s12877-025-06063-9).