Evaluation of novel urinary tract infection biomarkers in children

Abstract

Background: Pediatricians frequently use urinalysis to diagnose urinary tract infection (UTI) while awaiting urine culture results, but sensitivity and specificity of urinalysis are limited. This study evaluated the diagnostic accuracy of the antimicrobial peptides (AMPs) human α-defensin 5 (HD5) and human neutrophil peptides (HNP) 1-3 as novel UTI biomarkers in children.

Methods: We prospectively enrolled 199 pediatric Emergency Department or Urgent Care patients evaluated for a UTI. Urine concentrations of HD5 and HNP1-3 were measured by enzyme-linked immunosorbent assay. Urine culture was the reference standard. Sensitivities and specificities of leukocyte esterase (LE), HD5, HNP1-3, and test combinations were compared.

Results: For predicting positive urine culture, the areas under the receiver-operating characteristic curves for HD5 and HNP1-3 were 0.86 (95% confidence interval (CI): 0.81-0.92) and 0.88 (95% CI: 0.82-0.93), respectively. Compared to LE ≥ trace, the combination test "LE and HD5" increased specificity by 6% (95% CI: 3-10%) without decreasing sensitivity. In the subgroup whose urine was collected by a clean-catch method, combination tests "LE and HD5" and "HD5 and HNP1-3" increased specificity by > 10% compared to LE alone.

Conclusion: Urine AMP profiles are a promising novel strategy as an adjunct to urinalysis to aid UTI diagnosis in children.

Conflict of interest statement

The authors have no conflicts of interest or relevant financial relationships related to this manuscript to disclose.

Figures

Figure 1. HD5 and HNP1-3 concentrations in culture-negative and culture-positive urine samples (A/B), and ROC curves (C/D)

A/B, Horizontal bars represent median values and interquartile ranges. Gray circles and squares indicate individual data points. C/D, The diagonal line represents a test with no diagnostic value.

Figure 2. Comparisons of sensitivity and specificity of LE, HD5, and HNP1-3, alone and in combination

A, All study patients. B, Catheterization subgroup. C, Clean-catch subgroup. Graphs display the change in specificity of each individual or combination test compared to LE ≥ trace. Horizontal bars represent 95% confidence intervals. N/A, not applicable.