Research sparked by the growing trend of using multiplex molecular syndromic panels to diagnose urinary tract infection (UTI) in older adults suggests the tests may be causing clinical harm through misdiagnosis and unnecessary antibiotics, in addition to draining Medicare money, according to original research published in JAMA Network Open.
Details come from the Division of Healthcare Quality Promotion at the Centers for Disease Control and Prevention (CDC) in Atlanta and Seattle-Denver Center of Innovation for Veteran-Centered and Value-Driven Care, an initiative of the Veteran Administration's (VA's) Health Systems Research office and partnership of 65 clinician scientists and PhD methodologists.
Those familiar with the study said they hope it will be a catalyst for increased scrutiny and government regulation of multiplex molecular testing. In addition, they hope to see more independent research into the clinical value of the tests, many of which are laboratory developed tests.
"In 2023, CDC began receiving inquiries and anecdotal reports of this testing occurring in nursing homes from antibiotic stewards concerned about the unintended consequences of this testing for inappropriate antibiotic use," the study's lead author Kelly Hatfield, PhD, of the CDC told LabPulse via email. "This investigation was completed to understand the magnitude of this testing and to raise awareness of the frequency of the use and cost of multiplex testing for UTI in administrative claims data, as well as to describe the health care professionals and patient populations using this testing."
Inappropriate treatment
Nursing home residents inappropriately treated for asymptomatic bacteriuria (ASB) can experience adverse outcomes, such as the potential for colonization or infection with antimicrobial-resistant pathogens, adverse drug events, and Clostridioides difficile (C. diff) infection.
Inappropriate treatment of misdiagnosed UTI in patients with asymptomatic bacteriuria is already a substantial problem, particularly among nursing home residents, according to Drs. Margaret Fitzpatrick from Seattle-Denver Center of Innovation for Veteran-Centered and Value-Driven Care and University of Colorado School of Medicine in Aurora, CO, and epidemiologist Daniel Morgan from the University of Maryland School of Medicine and VA Maryland Healthcare System in Baltimore, who penned an editorial affiliated with the large-scale analysis of Medicare Part B claims data published November 26.
Among findings from the retrospective nationwide analysis of claims data, Medicare fee-for-service claims for multiplex testing with a primary diagnosis of UTI increased from 2 to 148 claims per 10,000 beneficiaries annually between 2016 and 2023, with 460,706 claims for UTI multiplex tests in 2023 (307,623 or 67% were among female beneficiaries around 77 years of age). The number of gold-standard urine cultures did not increase in correlation, according to the researchers.
Increased utilization
The rate of UTI multiplex claims among beneficiaries residing in a nursing home increased from 0.24 to 247.9 per 10,000 fee-for-service beneficiaries from 2016 to 2023, leading the researchers to conclude that high utilization of urine multiplex molecular tests in care settings with potentially limited antimicrobial stewardship support, such as nursing homes and urology clinics, is especially concerning.
In addition, "one of the most important findings from this study was that claims for urine multiplex molecular tests were 70 times more expensive than those for urine culture, emphasizing the likelihood of harm from increased costs and profit-driven health care," added Fitzpatrick and Morgan, who added the tests cost Medicare more than $269 million in 2023.
Algorithm tracked
The analysis found the median cost of UTI multiplex claims to be $585, ranging from $516 to $695 per claim, compared with $8 to $16 per claim for corresponding UTI urine culture claims, reported the researchers who developed an algorithm to identify line-item claims of interest to find out how frequently multiplex molecular syndromic panels are used to diagnose UTI among older Medicare beneficiaries.
Because there is no specific procedure code for identifying UTI multiplex tests, the algorithm probed for clinician office or laboratory services, for unspecified multiplex testing, and for claims with Current Procedural Terminology (CPT)-4 codes indicating the detection of an infectious agent using a nucleic acid probe.
Researchers excluded similar claims related to another infection type, such as panels specific to a respiratory or pneumonia infection, urogenital or anogenital infection, bloodstream infection, central nervous system infection, or gastrointestinal infection. Denied claims were also excluded.
Hatfield and colleagues noted that clinical specialties were limited to clinicians, and the specialties of advanced practice clinicians, such as nurse practitioners and physician assistants, were not able to be ascertained. After laboratories or pathologists, urology was the most common clinician specialty conducting this testing, Hatfield and colleagues said. Moreover, analysis was limited to fee-for-service claims and did not include data from the Medicare Advantage population.
Data lacking
"This cohort study identified important increases in the use of multiplex molecular syndromic panels for UTI, coupled with high costs to CMS, since 2016," wrote Hatfield and colleagues. "Clinicians should be aware of the lack of data supporting this testing and the potential to further contribute to inappropriate antibiotic prescribing."
The team also said additional monitoring and research are needed to determine the effects of multiplex testing to diagnose UTI on antimicrobial use and whether there are clinical situations in which this testing may benefit patients.
Furthermore, high-quality studies are urgently needed to develop standards for sample collection, processing, laboratory protocols, and reporting of results, Hatfield and Morgan added. Additional data are required to clarify what thresholds of bacteria in molecular tests correlate with UTI, identify associations between phenotypic and genotypic antimicrobial susceptibility tests, and quantify the impact of urine molecular tests on antibiotic use and resistance.
Payer note
"We advocate that Medicare and other payers consider not reimbursing for these non-FDA-approved and likely harmful tests and that medical societies highlight the lack of evidence for urine multiplex molecular tests in UTI clinical guidelines," they said.
In light of findings like these, reimbursement for molecular syndromic panel testing for UTI may continue to face uncertainty, unless clinics and molecular diagnostic laboratories can meet the complex requirements and criteria of payers.
Even a November consensus statement and systematic review addressing guidelines for the prevention, diagnosis, and management of UTI in pediatrics and adults pointed out that more research is required to determine the ideal role of molecular testing in complex and recurring urinary tract infections, especially to prevent unnecessary treatment of ASB, as molecular diagnostics cannot distinguish true infection from ASB. The consensus document was authored by scientists from 50 institutions in the U.S.
Authors of that consensus statement wrote that pressing research gaps remain, including the need for high-quality studies to validate novel diagnostic methods, optimize treatment durations, establish standard definitions, and refine antimicrobial stewardships strategies for ASB and multidrug-resistant organisms. Randomized clinical trials are underway to address the gaps.
Right test, right interpretation
Meanwhile, the CDC said the findings from the nursing home study support the importance of the CDC’s new Core Elements of Hospital Diagnostic Excellence, a framework for hospitals to make sure the right tests are ordered, interpreted, communicated, and acted upon appropriately to prevent patient harm. Education about the limitations of multiplex molecular tests for UTIs should occur across healthcare professional specialties and older adult populations.
"Ensuring that the right test is ordered for the right patient can limit excessive testing and overdiagnosis, improve antibiotic use, and decrease the risk adverse events and infection with antimicrobial-resistant organisms," Hatfield said.
