A Prospective, Observational Pilot Study of the Use of Urinary Antimicrobial Peptides in Diagnosing Emergency Department Patients With Positive Urine Cultures

Abstract

Urinary tract infection (UTI) often represents a diagnostic challenge in the emergency department (ED) where urine culture results are generally not available and other tests demonstrate limited sensitivity and specificity. Antimicrobial peptides (AMPs) are components of the innate immune system that have demonstrated increased urinary levels in response to infection both in children and in adults with chronic UTI. The objective of this study was to determine the relationship between urinary AMP levels and positive urine cultures in adult ED patients with suspected UTI. This was a prospective, observational study of adult ED patients with suspected UTI. Enzyme-linked immunosorbent assays were performed to measure urine levels of AMPs: human neutrophil peptides 1-3 (HNP1-3), human α-defensin 5 (HD5), human beta defensin 2 (hBD-2), and cathelicidin (LL-37). Comparisons between positive and negative cultures were performed using Wilcoxon rank sum tests and receiver operating characteristic curves, with calculation of area under the curve (AUC). Data were also analyzed for the older adult subgroup. Of 40 patients enrolled, 23 (58%) were ≥ 65 years, 25 were female (64%), and seven (17%) were nonwhite. Cultures were positive in 13 (32%), including seven in those ≥ 65 years old. HNP1-3, HD5, and hBD-2 levels were significantly higher in those with positive than negative urine cultures. Median HNP1-3 was 5.39 ng/mg (interquartile range [IQR] = 2.74 to 11.09) in positive vs. 0.81 ng/mg (IQR = 0.06 to 3.87) in negative cultures. Median HD5 was 4.75 pg/mg (IQR = 1.6 to 22.7) in positive versus 0.00 pg/mg (IQR = 0 to 2.60) in negative cultures, and median hBD-2 was 0.13 pg/mg (IQR = 0.08 to 0.17) in positive versus 0.02 pg/mg (IQR = 0 to 0.04) in negative cultures (p < 0.05 for all). Findings were similar for adults ≥ 65 years. The AUC was ≥ 0.75 for all three AMPs, both overall and in the older adult subgroup. LL-37 was not significantly higher in patients with positive urine culture. However, LL-37 expression is vitamin D dependent, and inadequate serum levels (< 30 ng/mL) were present in 72% of those tested. Urinary levels of HNP1-3, HD5, and hBD-2 are significantly greater in the presence of positive urine cultures in ED patients with suspected UTI. These findings are maintained in the high-risk subgroup of older adults.