An updated clinical approach to diagnosing urinary tract infections (UTIs) that considers five potential phenotype categories instead of the usual three could aid clinical management and better center patient needs, according to the authors of a new study in The Journal of Urology.
The current diagnostic paradigm includes UTI, asymptomatic bacteriuria (ASB), or not UTI, but the researchers believe these categories exclude for more ambiguous clinical cases, such as patients whose bacteria counts are low but who are symptomatic, or when nonspecific symptoms make it difficult to determine whether treatment with antibiotics is appropriate.
"Our findings suggest the need to reframe our conceptual model of UTI vs ASB to recognize clinical uncertainty and reflect the full spectrum of clinical presentations," Sonali D. Advani, MBBS, MPH, an associate professor of medicine in infectious disease at Duke University School of Medicine, in Durham, North Carolina, and her colleagues wrote. "Recent data suggest that UTI may present as a bidirectional continuum from asymptomatic bladder colonization to a symptomatic bladder infection," and some populations may lack the signs or symptoms specific to urinary tract or have chronic lower urinary tract symptoms (LUTS) that make it difficult to distinguish between ASB and UTI, they wrote.
Nitya E. Abraham, MD, an associate professor of urology at Albert Einstein College of Medicine and Montefiore Einstein in New York, agreed the current paradigm has room for refinement.
"The current classification system doesn't account for certain patients such as patients who have bothersome urinary symptoms, but urine testing comes back negative, or patients with positive urine testing, but aren't able to report the presence or absence of symptoms," Abraham, who was not involved in the new research, told Medscape Medical News.
Boback Berookhim, MD, a urologist at Northwell Health in New Hyde Park, New York, who was also not involved in the research, said the goal with this study appears to be better identifying who will need antibiotics.
"I think this is more of a forward-looking study in terms of trying to identify patients who currently may not be treated or may be over treated and better identifying subsets," Berookhim told Medscape Medical News.
However, he said the relevance of the work is far greater in hospitals than in outpatient settings.
"I think it's much more relevant in inpatient environments where a patient is in hospital and whatever antibiotics are being written are going to be overseen and you're going to see higher resistance patterns," Berookhim said. "For the average doctor who's seeing patients in the office and writing them prescriptions in the office, this doesn't really affect them."
Antibiotic Dilemma
A key issue in determining the best approach to UTI diagnosis is assessing the appropriateness of antibiotic treatment. Up to half of hospitalized patients have ASB, for which current practice guidelines advise against antibiotics, Advani and her colleagues noted. Yet many of these patients receive antibiotics regardless, and research has shown links between treatment and longer length of stay, antibiotic resistance, and infection with Clostridioides difficile.
The challenge comes with patients who do not fit easily into the existing categories. One includes patients who have positive urine cultures but whose symptoms, such as hypotension or fever, are not specific to the genitourinary tract.
While current guidelines advise against treating these patients with antibiotics, the patients are often older adults with cognitive impairment or delirium, and frontline physicians may err on the side of prescribing antibiotics because of their clinical uncertainty. That treatment can lead to tension with hospital antibiotic stewardship teams that recommend withholding antibiotics for those patients.
"These clinical scenarios highlight differences between the frontline clinicians' and antibiotic stewardship teams' definitions of 'asymptomatic,' highlighting the ambiguity of the term 'asymptomatic bacteriuria,'" Advani and her colleagues wrote.
A fever, for example, could signal a viral or bacterial infection or result from a nonurinary source, Abraham said. "The antibiotic stewardship team likely prefers to observe the clinical course and wait for more data to demonstrate need for antibiotics," she said. "Hence, there are conflicting priorities and confusion of when to treat with antibiotics for this common dilemma in patients presenting to the ER or urgent care."
Meanwhile, other patients, particularly women, may present with urinary symptoms and pyuria but have lab results revealing a colony count below the 100,000 CFU/mL threshold that would indicate antibiotic treatment.
"Some of these women are likely suffering from a UTI and may not receive treatment if clinicians focus primarily on the urine culture results," Abraham said. She pointed out the existence of other options than urine culture for better identifying UTI, such as urinary cell-free DNA or next-generation DNA testing of the urine. But she also said the 100,000 CFU/mL threshold should not be absolute.
"For example, I will treat patients for UTI with 10,000-50,000 CFU/mL if they also have UTI symptoms like blood in the urine, burning with urination, bladder pain, increased urgency or frequency, and the urinalysis shows a high white blood cell count," Abraham said.
Abraham also noted a third group outside the scope of the new study: People with urinary symptoms who don't undergo urine tests or who are treated empirically with antibiotics. "It is unclear whether those in this group truly have a UTI, but it is a common scenario that patients are unable to get urine tests and are treated with over-the-phone prescriptions to expedite treatment," she said.
Get on the BUS
The researchers conducted a retrospective study across one academic medical center and four community hospitals in three states to assess the feasibility of using five categories of UTI diagnosis: The three existing ones plus LUTS/other urologic symptoms (OUS) and bacteriuria of unclear significance (BUS). These additional categories arose out of an hour-long discussion with a focus group of experts across several disciplines.
The analysis covered the charts of 3392 randomly selected encounters out of 220,531 total inpatient or emergency department encounters between January 2017 and December 2019 in which adults received a urinalysis and urine culture order within the same 24-hour period. The patients' median age was 67 years, over half (59.6%) were women, and nearly a quarter (24.2%) had an underlying immunocompromising condition.
Most of the cultures were obtained from inpatients. Nearly a third (30.6%) were negative for culture, while 42.1% grew at least 100,000 CFU/mL of bacteria and 17% grew mixed flora.
Based on current criteria, 21.3% of the patients had a UTI, 20.8% had ASB, and 47.6% had no UTI. The remaining 10.3% had culture growth under 100,000 CFU/mL and, therefore, did not fit in any of these categories, "as there is no consistent guidance on whether to classify them as no UTI or ASB or contamination," the authors wrote.
When the researchers applied the new criteria, more than half of the cases of ASB (68%) were reclassified as BUS, and 28.9% of the no-UTI cases were reclassified as LUTS/OUS.
In a sensitivity analysis that examined samples with bacteriuria below the 100,000 CFU/mL threshold, nearly half the unclassified cases (43.3%) were reassigned as a UTI, increasing the proportion of patients with a diagnosed UTI from 21.3% to 25.8% of the total population. Of the remaining patients who had originally been unclassified, 14.2% were newly defined as ASB, and 42.5% became BUS.
Abraham said the addition of the BUS and LUTS/OUS categories has the potential to improve and individualize patient care. Clinicians can consider nonantibiotic therapies for the patients who had LUTS/OUS while they look into possible causes, while the BUS cases enable frontline clinicians and antibiotic stewardship teams to "meet in the middle" by monitoring those patients more closely in case symptoms worsen, she said.
The authors highlighted three key takeaways from their study, starting with the fact that nearly two thirds of patients who underwent testing for a UTI did not have signs or symptoms localized to the urinary tract — the ones reclassified as BUS.
"Hence, reclassifying patients as BUS may provide an opportunity to acknowledge diagnostic uncertainty and need for additional monitoring than ASB patients so as to promote a nuanced and patient-centered approach to diagnosis and management," the authors wrote.
Second, a third of patients initially classified as not having a UTI were reclassified into the new LUTS/OUS category because of their symptoms, such as a poor or intermittent stream, dribbling, hesitancy, frequency, urge incontinence, and nocturia. These patients would need further workup to determine the best approach to management.
Finally, the sensitivity analysis "suggested that lowering the bacterial threshold in some symptomatic patients may capture additional patients with UTI whose symptoms may be dismissed due to concern for contamination or attributed to LUTS rather than infection." Given that the 100,000 CFU/mL threshold is based on a single study in 1956, the authors suggested more research may help define better CFU thresholds to improve clinical care.
Berookhim said the study authors took a reasonable and thorough approach in how they tried to consider the best way to update the current diagnostic classification schema.
"I think using this as a jumping off point to look deeper is worthwhile," such as conducting randomized controlled trials to assess the use of new categories, he said. "Getting more granular than this, I think, would just muddy the waters and make it more difficult to make clinical decisions."
The research was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Advani reported consulting fees from Locus Biosciences, Sysmex America, GlaxoSmithKline, and bioMérieux. Abraham and Berookhim reported no relevant financial conflicts of interest.
Tara Haelle is a medical journalist based in Dallas.