The Problem

One does not have to practice urology for long to recognize how frequently our patients experience or think they may be experiencing a urinary tract infection (UTI). In an ideal world, we could perform a single test that quickly provides accurate information regarding the presence or absence of infection and, if present, the appropriate antibiotic(s) for treatment. Prompt and precise information would provide clinicians all the necessary data for consideration of treatment. Standard urine culture (Ctx) remains the gold standard for urinary tract infection across most hospital facilities, although it lacks many of these ideal characteristics.

Culturing of urine is limited by a multiday lag between the time of specimen collection and the final resulting information regarding presence of microorganism growth and antimicrobial susceptibility. If clinicians wait until Ctx results to consider treatment, the patient will likely continue to suffer with bothersome symptoms and run the risk of the infection worsening. As a practical matter, providers may empirically treat patients with an antibiotic after collecting the urine specimen. Some patients will be treated appropriately, but empiric treatment can result in overtreatment of patients with no infection, or insufficient and delayed treatment if the culture grows an organism not susceptible to the prescribed antibiotic, requiring the provider to prescribe a more appropriate medication.

Another example of how this may affect patients occurs in patients with nephrolithiasis and concurrent urinary tract infection. Intraoperatively obtained culture of renal stones in patients undergoing surgical stone removal frequently does not match culture data from preoperative voided urine culture.¹ Inaccurate culture data in patients undergoing stone procedures could be a contributing factor in postoperative infectious complications if the preoperative and perioperative antibiotics provided do not treat microorganisms contained in the stone.

The technique of Ctx clearly leaves room for improvement.

What Is Next-Generation Sequencing?

Next-generation sequencing (NGS) is performed using rapid-sequence polymerase chain reaction (PCR) of DNA from bacterial 16S rRNA genes.² Several commercially available companies offer this technology, and it is often covered by health insurance in the United States. Depending on the company used, NGS provides a test result in 24 hours. NGS has been utilized in studies of the urinary microbiome to disprove the previously held dogma that urine is sterile,² as well as in microorganism detection in other fields such as orthopedics when evaluating for joint infections.^3,4

How Does NGS Compare to Ctx in Clinical Urology Practice?

A 2017 study by McDonald et al compared microorganism detection in urine samples of both asymptomatic control patients and patients with symptomatic acute cystitis.⁵ Standard urine culture detected organisms in 13 of 44 (30%) symptomatic patients and 5 of 22 (23%) asymptomatic controls. Interestingly, NGS detected microorganisms in all but 1 patient, including the asymptomatic control patients. Specifically, NGS detected microorganisms in all 44 of 44 (100%) symptomatic patients and 21 of 22 (95%) controls.

Our group recently completed a prospective study evaluating concordance of microorganism detection between voided (or catheterized) urine and stone samples taken from patients undergoing surgical stone removal (ureteroscopy or percutaneous nephrolithotomy) using both Ctx and NGS.⁶ Of all 84 patients included, 33 (39%) had microorganisms detected in urine by Ctx vs 66 (79%) by NGS, and 27 (32%) had microorganisms detected in surgically removed stone by Ctx vs 40 (48%) by NGS. When evaluating concordance between urine and stone samples, the data suggest a large amount of discordance between Ctx and NGS. As seen in table 1, the highest proportion of concordance occurred between Ctx of urine and Ctx of stone samples (63% for exactly matching samples), with the next highest proportion of concordance between Ctx of surgically removed stones and NGS of those same stones (52% for exactly matching samples). Table 2 includes test characteristics for predicting concordance of both Ctx and NGS of urine samples to both Ctx of the surgically removed stone or NGS of the stone. The results reported in this table suggest that the test characteristics are not overly favorable for NGS when comparing to standard urine culture.

Is NGS the Future?

It is important to keep in mind that our study is based upon an assumption that standard urine culture is the optimal gold standard for microorganism detection, especially when looking at test characteristics reported in table 2. NGS more often detects microorganisms than Ctx in both urine and stone samples, and even standard urine culture will detect microorganisms in otherwise asymptomatic patients. Ctx lacks much in the ways of a gold standard test, but it remains to be determined if NGS has the capability of filling the gaps.

Further work still needs to be completed to determine if NGS should replace or be otherwise routinely incorporated into clinical practice. One major limitation of the above studies is the clinical relevance of the result obtained by NGS. NGS almost always detects some organism presence, making it challenging to determine what is a harmless colonizer vs a true infection. Over detection of clinically insignificant microorganisms may cause more harm than good, or make NGS unwieldy. If, however, the results could be clarified to appropriately identify clinically relevant microorganisms, then perhaps this technology could show a superiority. Further studies to define the clinical relevance of NGS for the urology community hold potential, but much work has yet to be completed.