Are Positive Urine Cultures Directly Correlated with Elevated Levels of Novel Biomarkers for Childhood Urinary Tract Infection?

Abstract

Urinary tract infection (UTI) in children is one of the most common bacterial infections that propels inappropriate antibiotic use. Long-term, potentially fatal complications can occur if not properly treated. Prompt investigation and appropriate treatment would prevent these complications. Although urine culture remains the gold standard investigation for UTI, its process is cumbersome and requires time (24–72 hours). Hence, there has been growing interest in the use of urinary biomarkers. However, some conventional urinary biomarkers detected on urinalysis have poor sensitivity values when used singly as a screening tool. Thus, the searchlight has shifted to the role of novel biomarkers in UTI diagnosis. This narrative review aimed to determine if elevated levels of these biomarkers directly correlate with positive urine cultures. A positive correlation may imply that these biomarkers could serve as novel UTI diagnostics and thus augment urine culture requests. Established and recent serum and urinary biomarkers show disparate predictive abilities for UTI and its related complications. Some have elevated differential levels in upper and lower UTI or febrile and non-febrile UTI. All studies that investigated these biomarkers established culture-positive UTI, highlighting a direct correlation between positive urine cultures and increased concentrations of the biomarkers in body fluids. Because certain uropathogens were less likely to be associated with pyuria, the sensitivities of some neutrophil-related novel biomarkers (such as urine neutrophil gelatinase-associated lipocalin and human neutrophil peptides 1–3) were reduced in cases of UTI caused by these bacteria. While levels of these novel biomarkers directly correlate with positive urine cultures, it appears that there is yet no standalone biomarker with the optimal sensitivity and specificity for UTI. Although these novel biomarkers are promising, translating their measurements into clinical practice with specific clinical utilities will take time. Novel methods interrogating high-throughput serum (and urine) metabolome data with positive urine cultures in a platform-agnostic manner (metabolome-wide approach) will help confirm and identify novel biomarkers that might capture specific aetiologic agents or shared pathways of related agents. The authors recommend that future research on UTI diagnostics should specifically focus on identifying highly sensitive and specific standalone novel biomarkers that can be easily applied as a point-of-care investigation.