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Sensitivity And Specificity Of Leukocyte Esterase Thresholds In Point-Of-Care Decision Making For Suspected Uti
Evan Cross, DO, Michelle Mitchell, MD, Jonathan Ellison, MD, Anika Nelson, MD, sri S. chinta, MBBS, MSCI, Glenn Bushee, MS, BS, Amy Pan, PhD, Shannon Baumer-Mouradian, MD, Melodee Liegl, MA, Lia Christine Bradley, MSN, Sadia Ansari, MD, Carissa Redmon Battle, MD, Kwesi Asantey, MD.
Medical College of Wisconsin Affiliated Hospitals, Milwaukee, WI, USA.

BackgroundUrinalysis (UA) is a vital diagnostic tool for pediatric patients presenting with suspected urinary tract infection (UTI). Literature indicates that UA is highly predictive of UTI or lack thereof when leukocyte esterase (LE) and nitrites are concordant. Diagnostic uncertainty exists when LE and nitrates are discordant. In the setting of nitrite-negative UA, we evaluated the sensitivity and specificity of pre-defined LE thresholds compared to an outcome of a positive urine culture. Furthermore, we sought to define sub-group sensitivities and specificities across age, specimen type and presence of fever.MethodsWe performed a retrospective chart review of patients aged 0 - 18 years who provided urine for suspected UTI from January to December 2019-2020 across all health care sites (primary care, urgent care, and emergency department) and had both UA and urine culture performed through clean-catch or catheterized samples. Patient demographics, presenting findings, and presenting location were obtained from electronic medical records. UTI was defined as ≥50,000 colony forming units of single uropathogen on culture. Contaminated or incompletely speciated urine cultures were excluded. Additionally, patients with neurogenic bladder, need for intermittent catheterization, recent genitourinary intervention, history of vesicoureteral reflux or nephrolithiasis were excluded. Primary analysis tested performance of LE as ordinal variable (trace, small, moderate, large) compared to gold standard of positive urine culture. Receiver operating characteristics (ROC) for LE as an ordinal variable were performed for the entire cohort and adjusted for age group [0 - 60 days, > 60 days - < 2 years, 2 years - <12 years, and >12 years), specimen type, and presence of fever. Statistical analyses used Fischer’s exact test for categorical variables and Mann-Whitney for continuous variables, with statistical significance defined by p value < 0.05.ResultsA total of 5,848 patients were considered for analysis. We excluded 20 patients due to urine specimen collected via cystoscopy or unspecified method, 1264 patients due to urine culture with contaminant listed as first specimen, and 678 patients due to incompletely speciated urine culture. Of the remaining 3,891 patients, 554 (14.2%) had positive urine culture. We calculated test parameters for varying thresholds of LE positive results.

LE Positive Threshold
TraceSmall, 1+Moderate, 2+Large, 3+
Sensitivity (%)92.181.653.323.5
Specificity (%)69.881.891.297.9
PPV (%)33.642.650.064.7
NPV (%)98.296.492.288.5
Increasing LE thresholds were significantly associated with an increased proportion of positive urine cultures (p < 0.001, Figure 1). ROC curves for LE as an ordinal value found strong performance based upon area under the curve (AUC) for the entire cohort (AUC = 0.8687) and models adjusting for age group, specimen type, and fever in the model (AUC = 0.9186).

ConclusionsTest performance for nitrite-negative UAs varies based upon LE threshold, where increasing LE threshold is more likely to yield positive urine culture. These data can inform point-of-care decision making for suspected UTI, allowing providers to incorporate LE threshold along with other clinical characteristics when deciding upon treatment.
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