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. 2023 Jun 16;76(12):2070-2076.
doi: 10.1093/cid/ciad099.

Current Pyuria Cutoffs Promote Inappropriate Urinary Tract Infection Diagnosis in Older Women

Manu P Bilsen  1 , Margaretha J Aantjes  1 , Esther van Andel  2 , Janneke E Stalenhoef  3 , Cees van Nieuwkoop  4   5 , Eliane M S Leyten  6 , Nathalie M Delfos  7 , Martijn Sijbom  5 , Mattijs E Numans  5 , Wilco P Achterberg  5 , Simon P Mooijaart  8 , Martha T van der Beek  9 , Christa M Cobbaert  2 , Simon P Conroy  10 , Leo G Visser  1 , Merel M C Lambregts  1
Affiliations

Current Pyuria Cutoffs Promote Inappropriate Urinary Tract Infection Diagnosis in Older Women

Manu P Bilsen et al. Clin Infect Dis. .

Abstract

Background: Pre-existing lower urinary tract symptoms (LUTS), cognitive impairment, and the high prevalence of asymptomatic bacteriuria (ASB) complicate the diagnosis of urinary tract infection (UTI) in older women. The presence of pyuria remains the cornerstone of UTI diagnosis. However, >90% of ASB patients have pyuria, prompting unnecessary treatment. We quantified pyuria by automated microscopy and flowcytometry to determine the diagnostic accuracy for UTI and to derive pyuria thresholds for UTI in older women.

Methods: Women ≥65 years with ≥2 new-onset LUTS and 1 uropathogen ≥104 colony-forming units (CFU)/mL were included in the UTI group. Controls were asymptomatic and classified as ASB (1 uropathogen ≥105 CFU/mL), negative culture, or mixed flora. Patients with an indwelling catheter or antimicrobial pretreatment were excluded. Leukocyte medians were compared and sensitivity-specificity pairs were derived from a receiver operating characteristic curve.

Results: We included 164 participants. UTI patients had higher median urinary leukocytes compared with control patients (microscopy: 900 vs 26 leukocytes/µL; flowcytometry: 1575 vs 23 leukocytes/µL; P < .001). Area under the curve was 0.93 for both methods. At a cutoff of 264 leukocytes/µL, sensitivity and specificity of microscopy were 88% (positive and negative likelihood ratio: 7.2 and 0.1, respectively). The commonly used cutoff of 10 leukocytes/µL had a poor specificity (36%) and a sensitivity of 100%.

Conclusions: The degree of pyuria can help to distinguish UTI in older women from ASB and asymptomatic controls with pyuria. Current pyuria cutoffs are too low and promote inappropriate UTI diagnosis in older women. Clinical Trials Registration. International Clinical Trials Registry Platform: NL9477 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9477).

Keywords: asymptomatic bacteriuria; microscopy; pyuria; urinary tract infection; urine flowcytometry.

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Conflict of interest statement

Potential conflicts of interest. M. M. C. L. reports grants or contracts as the principal investigator on the Embrace Study. L. G. V. reports grants or contracts as the co-investigator on the Embrace Study. J. E. S. reports consulting fees from Viiv Expert Board HIV, unrelated to this manuscript; payment or honoraria from Nederlandse Internisten Vereniging: Centraal Onderwijs Interne Geneeskunde Infection and Immunity (a course for internists in training); and participation as the Chair of Dutch Infection Prevention Guideline Committee “Urinary Catheterization.” M. E. N. reports payment for expert testimony for the development of guidelines for primary and secondary care, focusing on GERD and Dyspepsia, Ondansetron, and Non-Alcoholic Fatty Liver Disease, and is a committee member for these guidelines (paid to author); unpaid membership to Network Academic Primary Care, the Netherlands; the Nederlands Huisartsen Genootschap Primary Care Practice Accreditation Board; and the Advisory Board of SIR Institute for Pharmacy Practice and Policy. S. P. C. reports royalties for textbook editing on geriatric emergency medicine, including urinary tract infections; consulting fees as clinical lead of the UK Frailty Improvement Network; and travel support for teaching or speaking on geriatric care across Europe. C. M. C. serves as Chair of the International Federation of Clinical Chemistry and Laboratory Medicine Scientific Division (independent) and reports receipt of equipment, materials, or services from Sysmex Corporation for reagents for flowcytometric measurements of samples on the Sysmex urine flowcytometry analyzer at the Clinical Chemistry and Laboratory Medicine Department, as reported under “funding.” All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Overview of screening and selection process. All patients in the control group were asymptomatic. Abbreviations: ASB, asymptomatic bacteriuria; LUTS, lower urinary tract symptoms; UTI, urinary tract infection.
Figure 2.
Figure 2.
Receiver operating characteristic curves for automated microscopy (A) and urine flowcytometry (B). For both diagnostic methods, the number of leukocytes (per µl) was used as the test variable and our stringent UTI definition was used for determining disease status. The true positive rate (sensitivity) was plotted against the false positive rate (1-specificity) for different pyuria cutoffs. The area under the curve was 0.93 for both methods. The reference line is represented by the dotted line. Abbreviation: UTI, urinary tract infection.
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