Molecular Testing For Urinary Tract Infection (UTI)
Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement Trends1Molecular Testing forUrinary Tract Infection (UTI):2020 Update on Clinical Utilityand Reimbursement TrendsAuthor: Tammy LeythamEditor: Liz CareyDARK Daily Laboratory and Pathology News @ darkdaily.comwww.darkdaily.com 2020 Dark Intelligence Group, Inc.
2Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement TrendsTable of ContentsIntroduction3Chapter 1: P roblems and Limitations of Culture-Based Testingfor UTI in Contrast to Molecular Testing4Chapter 2: R ecent Clinical Trials Focused on UTI DiagnosticsUsing Rapid Molecular Testing6Chapter 3: Reimbursement Trends and Cost Versus Value in Molecular Testing for UTI9Conclusion11References12About Thermo Fisher Scientific14About DARK Daily15About The Dark Intelligence Group Inc., The Dark Report, andExecutive War College on Laboratory and Pathology Management16Terms of Use17www.darkdaily.com 2020 Dark Intelligence Group, Inc.
Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement Trends3IntroductionUrinary tract infection (UTI) is the second most common type ofinfection in the US, accounting for 10.5 million office visits per yearand 50 percent of all Medicare hospital admissions.1, 2 UTI is amongthe most common cause of bacterial infections in long-term carefacility residents.Effective treatment of a UTI depends on the accurate identificationof the pathogen(s) and the correct choice of antibiotic(s).3 Althoughculture-based clinical laboratory testing methods remain the goldstandard for diagnosing UTI in both research and clinical laboratories,the clinical utility of such methods continues to be called into question.4About 60 percent of all women will develop a UTI during theirlifetime.5 Of those, 25 to 30 percent are likely to have a repeatinfection.6 These infections can be devastating. Complicated oruntreated UTIs frequently cause sepsis in older adults above 65 yearsof age, with mortality ranging from 25-60%.7 About 50 percent of allsepsis cases among nursing home residents originate from UTIs.8“When you look at that, you start to get an understanding of thesignificance of the problem,” says David Baunoch, PhD, ChiefScientific Officer at Pathnostics, which has conducted several clinicaltrials using a rapid molecular test to determine whether a UTI test thatanalyzes DNA performs better than traditional culture-based tests.9This white paper explains the experiences of early adoptersof rapid molecular testing for UTI, provides an update on the statusof clinical utility of these tests, and describes healthcare settingswhere molecular testing for UTI is expected to be of value toimproving outcomes.www.darkdaily.com 2020 Dark Intelligence Group, Inc.
4Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement TrendsChapter 1:Problems and Limitations ofCulture-Based Testing for UTIin Contrast to Molecular TestingCurrent culture-based methods for detecting UTI pathogens haveseveral limitations. Those limitations include subjectivity andspecificity, length of time to results, and missed positive samples.Culture-based methods of identifying uropathogens are dependenton whether or not the pathogen can grow on an agar plate. Thesetests are performed by placing a drop of urine on a culture plate andincubating it overnight. The culture-based test determines positiveor negative based on the presence or absence of uropathogens thefollowing morning.“It’s really a biased result,” Baunoch said. “It’s inherently based onwhether or not the particular group of organisms can grow out in thatcultural medium in the required time. The problem really comes downto the fact that a large number of Gram-negative and especially Grampositive organisms cannot grow in those culture conditions.”“First, we look at the test in general: a traditional culture test for UTIs.If you’re 30 percent false negative, you know you have a significantproblem,” Baunoch said. “It’s not only a false negative that’s important.It’s also the number of additional organisms that are missed.”Properly implemented and applied, molecular diagnostic technologiesenable the microbiology laboratory to determine a positive infection,the type of infection, and what will treat that infection, with shorterturnaround time than traditional culture-based testing methods.10UTIs are often polymicrobial, meaning that multiple uropathogens arewww.darkdaily.com 2020 Dark Intelligence Group, Inc.
Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement Trends5responsible for the diagnosis. A recent study11 that compared traditionalurine culture testing to multiplex polymerase chain reaction (PCR)molecular testing, run in parallel, showed that the molecular methodfound six additional polymicrobial cases for every one found usingurine cultures, explained Baunoch.The multiplex panel used in the study tested for 31 bacteria, and PCRand urine culture together identified 29 different bacterial pathogens.PCR detected 24 bacteria, while culture detected 21 different bacteria.Associated UrologicalSpecialists began usingthe PCR-based moleculartest in 2016.There, thetest is already standardpractice in cases ofcomplicated UTIs, menand women over the ageof 60, recurrent infections,patients who are onsteroids or have diabetes,or those who have stones.Associated UrologicalSpecialists consists of agroup of 17 physicianswho order 200 to 300molecular tests permonth.“In the simple setting, westill use urine culture. Atthis point, we’re selectingonly patients who wethink have complicatedUTIs or features thatwould put the patient inmore harm if we didn’tidentify the correctbacteria right from theget-go.”—Raj Patel, MDPresident andChief Medical Officer,AssociatedUrological Specialists“Molecular methods have extreme sensitivity and specificity that allowfor the identification of additional pathogens that are missed,” Baunochexplained. “This becomes an issue especially in these patients whoare being hospitalized with urosepsis. They often tend to be complexinfections with multiple organisms present.”Raj Patel, MD, President and Chief Medical Officer at AssociatedUrological Specialists in Chicago, explained the adoption of moleculartesting in his practice.12Clinicians were aware that culture-based tests were not 100 percenteffective in identifying bacteria that could cause infection, Patel said.That especially was true for prostatitis, he said, where a patient hadsymptoms likely related to an infection, but the urine culture wouldnot identify the organism. Culture-based tests also did not pick upinfections in patients who had been exposed to antibiotics.But, Patel said, “We didn’t realize how far off the mark we were untilthe PCR-based studies, as well as our own experience in seeing menand women who have recurrent infections and seeing the true culpritsidentified in the PCR-based tests.”Patel’s team also saw patients who had already been on antibiotics;no bacteria grew in culture. “In those cases, they may be treated withmultiple broad-spectrum antibiotics intravenously until a certain timeperiod or if we’re able to find out exactly which bacteria it grows out,”he said.www.darkdaily.com 2020 Dark Intelligence Group, Inc.
6Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement TrendsChapter 2:Recent Clinical TrialsFocused on UTI DiagnosticsUsing Rapid Molecular TestingRapid molecular tests are emerging as a strategy for controllingthe impact of infectious diseases. New diagnostic methods may bepromising.One such test is the PCR-based Guidance UTI test which consistsof both multiplex-polymerase chain reaction (M-PCR) and pooledantibiotic susceptibility testing (P-AST). The test is explained assimultaneously diagnosing and guiding antibiotic treatment forrecurrent, persistent, or complicated UTIs. According to Baunoch,Guidance is affiliated with 4 million worth of clinical trials and hasbeen used in well over 100,000 patients.For example, an article published in the February 2020 edition ofUrology13 explains the results of a 582-patient retrospective trial. Thestudy showed that multiplex PCR is not inferior to traditional urineculture, and in fact detected bacteria in 36% of symptomatic patientswho had a negative urine culture.In addition, multiplex PCR detected more polymicrobial infectionsthan urine culture (in 28% of patients compared to 7% of patients).In addition to higher detection rates, PCR can provide results in aslittle as 6 hours, while cultures take 48 or more hours. The rapid,accurate identification of uropathogens offered by PCR can facilitatemore appropriate and efficacious treatment and may improve clinicalcare and outcomes.14In 2020, Pathnostics expects to publish the results from twoadditional trials, one consisting of 511 patients and the other ofwww.darkdaily.com 2020 Dark Intelligence Group, Inc.
Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement TrendsWhen CapstoneHealthcare beganmolecular testing forUTIs in August 2018,they worked with onesmall urology group.Now, in addition tourology, Capstone workswith urgent care clinics,long-term care, familypractice, pain clinics,and a wide range ofproviders. Capstone hasalso expanded the numberof microorganisms andantibiotic resistance genesin the UTI test.Capstone describes itsMolecular UTI test as anoptimized UTI panel thatlooks beyond the culture.“We started out lookingat 17 organisms. Withina year and a half, useof molecular testing wasapplied to antibioticresistance genes, sexuallytransmitted infections, andantibiotic treatment chartswere added. It’s everevolving and as a result ofthe progress, test demandand volume have grown.”—Trisha LauterbachDirector of LaboratoryOperations,Capstone Healthcare766,383 patients, according to Baunoch. Georgia-based CapstoneHealthcare will also begin working on a large study with Pathnosticsand Thermo Fisher.Capstone conducts its own in-house testing, describing the service asan optimized UTI panel that offers rapid turnaround time comparedto traditional microbiology techniques. For the first six months ofuse, Capstone compared the sensitivity of every molecular test to aculture-based test, run in parallel.“Specifically with our molecular UTI tests, we currently lookat 39 of the most common pathogens that we see in our patientpopulation that contribute to urinary tract infections and antibioticresistance gene markers for 10 classes of antibiotics,” explainedTrisha Lauterbach, Director of Laboratory Operations forCapstone Healthcare.15“We use an antibiotic treatment chart on our report that shows whichmicroorganism and antibiotic resistance genes have been detected,”Lauterbach said. “The report provides antibiotic recommendationsbased on commonly used antibiotics to treat the infection and takesinto account any antibiotic resistant genes detected.”“By using molecular PCR, we are able to identify micoorganismsthat traditional culture cannot, such as fastidious organisms andSTI,” Lauterbach said.” We can also identify individual microbesin polymicrobial infections, providing the physician valuableinformation to make treatment decisions.”Turnaround time is an important consideration for researcherslooking to enhance the quality of patient care. In this case, theimportance of the shortened time to results and start of treatmentcannot be overstated in the value of molecular diagnostic tests.Capstone Healthcare runs about 1,000 molecular UTI tests eachmonth and aims for a 24-hour turnaround time, Lauterbach said,www.darkdaily.com 2020 Dark Intelligence Group, Inc.
8Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement Trendsalthough, “our average turnaround time right now is about seven hoursfrom the time we receive the sample here at the laboratory.” Treatmentoptions at the physician’s disposal are much greater when they getinformation at the point of care rather than waiting from three to fivedays to get results, she said.In the case of Patel’s Associated Urological Specialists, whichmaintains an in-house laboratory, the turnaround time for test results isusually within 24 hours, according to Patel.“We don’t have to treat empirically and wait like we do with urineculture where it can take two to three days, and sometimes we can’teven identify the exact or all the bacteria that cause issues,” Patel said.“We see a significant improvement in tailoring the care and beingmuch more selective on which antibiotics are appropriate to use on thepatients with these infections.”Patel sees practical, useful applications of the molecular test,especially for older patients who are dependent on others fortransportation and may not be able to get to a clinic. For thispopulation, an untreated infection left to progress can cause otherhealth issues and hospitalization.A patient can begin antibiotics based on symptoms, then provide asample within five days. The molecular test is sensitive enough toidentify the causative agent(s)—even though a patient is on antibiotics.If used with urine culture, more often than not, the presence ofantibiotics in those bacteria won’t allow bacteria to grow on the cultureimmediately, Patel explained.Added Baunoch, “While the molecular test provides initialinformation, a phenotypic test is used to ask the question ‘does thatorganism actually respond to the antibiotic or not.’”www.darkdaily.com 2020 Dark Intelligence Group, Inc.
Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement Trends9Chapter 3:Reimbursement Trends andCost Versus Value inMolecular Testing for UTIInsurers and other payers have acknowledged the benefit of moleculardiagnostic testing, which includes deoxyribonucleic acid-(DNA) orribonucleic acid-(RNA) based analysis (with or without amplification/quantification). This is because of the sensitive, specific, and timelyidentification of organisms (relative to that of traditional culture-basedmethods).A minireview in the Journal of Clinical Microbiology explains that“selecting the right test for the clinical setting involves the evaluation oftest performance, laboratory feasibility, and cost versus value. To ensurethat the diagnostic technology selected is appropriate for the clinicalsetting, it is important to consider testing volumes, diagnostic yield, andthe feasibility of performing the test in the laboratory setting.”16Additionally, “While a simple analysis can be used to compare costsand charges for existing diagnostic tests versus new rapid diagnostictests, a true cost-value analysis should include “back-end” cost savingsof decreases in resource utilization (antimicrobials, unnecessaryadmissions, and lengths of stays), as well as effects on morbidity andmortality rates.”17In the case of molecular testing for UTIs, the higher payer cost ofmolecular assays must be considered alongside the value of potentialdownstream savings and improvement in the patient’s quality of care.UTIs have just over a 13 billion impact on the healthcare system ingeneral, so when you look at costs, it is important to first understandthe true impact, Baunoch said.www.darkdaily.com 2020 Dark Intelligence Group, Inc.
10Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement TrendsFor patients, the problem is not only the UTI itself but the threat ofurosepsis, which is a complication of UTI. More than half the casesof urosepsis among older adults are caused by a UTI, according to theSepsis Alliance, a charitable advocacy organization.18A Spring 2020 release of research published in the JOJ Urologyand Nephrology explains that utilization of M-PCR and P-AST orurine specimens was associated with at 13.7% decrease in hospitaladmissions and/or emergency department utilization when comparedto the use of standard urine cultures (SUC) testing. The utilizationresults that were reported occurred during the course of home-basedprimary care.19Patel suggests that outpatient settings and assisted living facilities willbenefit similarly.Adds Baunoch, the application may be of value to long-term carefacilities particularly.Despite the potential benefits of M-PCR and P-AST testing, paymentdenials and delays are significant concerns. Such tests may requireprepayment medical review but may be covered by Medicare, andin some states, by Blue Cross and other private payers.Molecular-based tests are reimbursed at a higher rate compared tothe traditional, economical standard culture. The advantage is inappropriately diagnosing the patient to ensure right treatment at theright time, Baunoch said.“We pay close attention to reimbursement trends. Commercial[insurance] and Medicare both continue to reimburse,” saidLauterbach. “As more of us are conducting clinical studies andshowing the true clinical utility and validity of the testing, it willcontinue to be reimbursed and continue to be used in clinical practice.”www.darkdaily.com 2020 Dark Intelligence Group, Inc.
Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement Trends11ConclusionMolecular tests are becoming more routine as diagnostic tools, withmany now covered by Medicare and commercial insurers. In certaincircumstances, molecular diagnostics may be positioned to becomestandard tests.Toward urinary tract infection, UTI-related urosepsis, and reducingthe related healthcare costs of both, there is a growing body ofevidence around real-time polymerase chain reaction (RT-PCR)technology. Molecular tests based on PCR technology identifyuropathogens traditionally missed by culture-based tests.Driven by urgent, unmet analytical and clinical care needs, theadoption of the rapid molecular test—particularly RT-PCR forurinary tract infection control and treatment—has importantimplications for home-based primary care, as well as assisted livingand long-term care facilities, and the hospitals that serve thesepatient populations.www.darkdaily.com 2020 Dark Intelligence Group, Inc.
12Molecular Testing for Urinary Tract Infection (UTI):2020 Update on Clinical Utility and Reimbursement TrendsReferences1. F lores-Mireles, A L, et al. (2015). Urinary tract infections:epidemiology, mechanisms of infection and treatment options.Nature Reviews Microbiology 13:269–284. 77/2. Baunoch, D. (2018). Reducing Time to Result for Urinary TractPathogen Detection Utilizing Real-Time PCR Technology. Webinar.https://www.whitehatcom.com/Fisher/Speaker Slides/ReducingUTI Detection Time D Baunoch 053018.pdf3. Garnacho-Montero, J., et al. (2007). Mortality and morbidityattributable to inadequate empirical antimicrobial therapy in patientsadmitted to the ICU with sepsis: a matched cohort study. Journal ofAntimicrobial Chemotherapy 61 (2):436–441. 694. Price, T., et al. (2016). The Clinical Urine Culture: EnhancedTechniques Improve Detection of Clinically RelevantMicroorganisms. Journal of Clinical Microbiology 54 65. U rology Care Foundation, the Foundation of the AmericanUrological Association. (2019). What is a Urinary Tract Infection(UTI) in Adults. urinary-tract-infections-in-adults6. H arvard Women’s Health Watch. (2019). When Urinary TractInfections Keep Coming Back. hen-urinary-tract-infections-keep-coming-back7. Peach, B, et al. 2016. Risk Factors for Urosepsis in Older Adults.Gerontology and Geriatric Medicine. 64/8. B aunoch, D. The Development o
Molecular Testing for Urinary Tract Infection (UTI): 3 2020 Update on Clinical Utility and Reimbursement Trends Introduction Urinary tract infection (UTI) is the second most common type of infection in the US, accounting fo
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