A new smartphone app and and lab kit can identify urinary tract infections (UTI) in an hour, with remarkable detail. The app, from UCSB researcher Michael Mahan's and Stanford’s Tom Soh’s teams, can give surprising detail with which to guide therapy as well.
At least half of women will develop a urinary tract infection (UTI) during their life. UTIs account for 25% of the cases of sepsis, and sepsis is a major cause of death, higher than heart attacks, diabetes, or breast cancer.
Besides being speedy and easy to use, diagnosing a UTI accurately down to what the organism is, will be inexpensive. Formally called a smartphone-based real-time loop-mediated isothermal amplification (smaRT-LAMP) system, it is based on nucleic acid detection. The assay uses simple equipment and is designed for point-of-care testing in low-resource settings.
The test involves a reusable kit with a hot plate, LED lights and a cardboard box, costing less than $100 for all the necessary equipment, and a smartphone to measure the chemical reaction of the tests.
The chemical reagents cost $1.13 per test, or $10-15 for a panel that will identify the most common bacteria causing such infections. It will be able to provide clinically useful information in an hour, compared to 18-28 hours for results from a traditional clinical microbiology lab, which has to first grow the bacteria in cultures.
The original study “Smartphone-based pathogen diagnosis in urinary sepsis patients” was published in the journal EbioMedicine. The research was funded by grants from the National Institutes of Health’s National Heart, Lung, and Blood Institute, with additional support from the Chan-Zuckerberg BioHub and the Bill and Melinda Gates Foundation.
The main caveat is that this was a pilot study in mice and only in 10 human patients. But identifying whether a patient has an E. coli infection or one from Pseudomonas or Klebsiella (or other) would be very helpful for clinicians.
The Bacticount app is free, open-source, with a tutorial, and is available so far for Android phones from the Google Play store.
There’s a big push from the World Health Organization for rapid, accurate, inexpensive point-of-care (POC) diagnostics. They recently came out with an Essential Diagnostics List including tests for anemia, diabetes, and well as major infectious diseases (TB, malaria, and HIV).
Dr. Madhukar Pai , Director of McGill Global Health, has been a strong advocate for the Esssential Diagnostics List and POC testing, especially for tuberculosis. He’s noted that while diagnostics influence 70% of health care spending, only 3-5% of health spending is targeted to diagnostics.
Clinical value
Only about half of UTIs are accurately diagnosed by symptoms. That increases to 73% with adding a urine dipstick assay. Urine dipsticks are inexpensive (<50 cents), but hospitals charges vary widely for even this simple test from $32-92. Also, their accuracy is quite variable. A negative dipstick for nitrates and leukocyte esterase (a test for pus in the urine) is pretty good in ruling out an infection. A positive test is less reliable and needs further evaluation.
A key finding in this study was that in patients with a blood stream infection (sepsis) from their UTI, the same organism was isolated from blood and urine. This means that, in caring for someone critically ill with sepsis, you could have a day’s head start in knowing what bacteria was causing their infection. This could help guide empiric antibiotic therapy and save lives. This Sepsis Awareness month is a good time to be reminded of the need for urgency in recognizing and responding to sepsis.
Also, in this limited pilot sample, there were no false positives—urine isolates matched blood isolates perfectly.
I’m particularly excited by these results in terms of potential for better evaluating patients for sepsis. Quickly knowing what the infecting bacteria is would be a big help, as some types of isolates can be harder to treat than others. On the other hand, this assay will not replace the need for culture and sensitivities on such patients, to know specifically what the best antibiotic would be for their infection.
POC testing is of less value in settings with high levels of antibiotic resistance, as was seen in this Thai study, where there was a 20% prevalence of quite resistant ESBL (extended‐spectrum β‐lactamase) organisms.
Before we had such problems with antibiotic resistant organisms, recommendations were to not do urine cultures on women with mild symptoms, except during pregnancy, as most infections were due to E. coli and most antibiotics worked. Dr. Lynn Fitzgibbons, an infectious diseases physician dealing with underserved populations, notes that this test will be very helpful for her clinic patients for whom cultures are unaffordable:
The provider could combine the information available from the rapid urine test with their knowledge of local resistance patterns to improve the likelihood that a patient leaves that screening visit with the right antibiotic.
Cost and alternatives
BioFire Diagnostics' FilmArray panels, a type of multiplex PCR test, are increasingly used in hospitals for much of their standard microbiology identification. They can also do testing in an hour for an array of pathogens in blood, stool, and respiratory secretions (but not urine).
BioFire’s assay has the large advantage of being able to detect viruses as well as bacteria. The downside is the cost, which was ~$129 per panel. Their stool screen, for example, costs twice as much as conventional testing for stool isolates. For blood cultures, that would come to ~$1,100 per culture.
Yet multiple studies indicate that these PCR tests are cost-effective and improve antibiotic stewardship efforts by more quickly focusing treatment.
The list price on the BioFire FilmArray machine was $49,000. None of the hospitals I’ve worked at in the past several years—all community hospitals—have had this technology available.
The other technology increasingly adopted by hospital labs is MALDI‐TOF (Matrix‐assisted laser desorption ionization time‐of‐flight mass‐spectroscopy). Again, there are high equipment costs, though a Johns Hopkins study found it would result in savings. A University of Michigan study found that, in addition to cost savings, MALDI-TOF plus antibiotic stewardship review and intervention decreased mortality for patients with bloodstream infections. Another found that the time to identification of a blood culture isolate was 40.9 h by conventional assay vs 6.6 h by MALDI-TOF.
Estimates of the global market for point-of-care diagnostics range from “$27.5 billion by 2018 at an estimated compound annual growth rate (CAGR) of 9.3% from 2013–2018.” Others estimate growth of $38 billion to 40.5 billion by 2022. Major players in diagnostics are Abbott (US), Roche (Switzerland), Siemens (Germany), Danaher (US), Becton, Dickinson, and Company (US), and Johnson & Johnson (US).
Conclusion
This smaRT-LAMP system to identify the specific bacteria causing a urinary tract infection—and possibly an associated blood stream isolate—is a very exciting, clinically useful advance and warrants speedy further study. It should help speed the diagnosis of infection and target more appropriate antibiotic therapy.
