Urinary tract infections (UTIs) are associated with significant morbidity. We rely on clinical presentation, urinalysis, and urine culture to diagnose UTI. To differentiate between lower UTI and pyelonephritis, we depend on the clinical presentation. In the extremes of age and in immunocompromised individuals, clinical presentation is often atypical posing a challenge to diagnosis. In the elderly, the high prevalence of asymptomatic bacteriuria is another confounder. We conducted a search of publications to find novel biomarkers to diagnose UTI and to ascertain its severity. We searched PUBMED, MEDLINE and SCOPUS databases for studies pertaining to novel biomarkers and UTI. Two reviewers independently evaluated the methodology of the studies using the STARD (Standards for Reporting of Diagnostic Accuracy) criteria. We have identified procalcitonin as a biomarker to differentiate lower UTI from pyelonephritis in the pediatric age group. Elevated serum procalcitonin levels can result in early and aggressive treatment at the time of presentation. Interleukin 6 has also shown some promise in differentiating between lower UTI and pyelonephritis but needs further validation. Lastly, given the paucity of data in certain subgroups like diabetics, kidney transplant recipients, and individuals with spinal cord injury, further studies should be conducted in these populations to improve diagnostic criteria that will inform clinical management decisions.

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