Comprehensive Review of Recurrent UTI Testing Options: Emerging Trends

Recurrent UTI testing requires more serious approach than a simple OTC UTI test strip that is often misused and therefore could be inaccurate. For years, researchers and physicians have been struggling to find better ways to better identify the pathogens causing recurrent UTIs.

It is also important to be able to differentiate between a chronic UTI caused by bacterial biofilms that often do not show up on traditional tests, from a recurrent UTI (when a patient keeps re-infecting themselves) and proper testing could help.

Unfortunately, even the urine culture tests are not always accurate and can identify the pathogens as some researchers state. This prompts the medical diagnostic industry to look for alternative recurrent UTI testing options.

This post is based on the 2017 research article New and developing diagnostic technologies for urinary tract infections, that we thought would be great to “translate” into laymen English, we also added some information that we linked to directly and in references.

Recurrent UTI Testing Research is Critical

More than half of antibiotics prescribed in the US are either the wrong antibiotic or not needed at all. In addition, we overuse antibiotics in livestock. This has led to a surge in “superbugs:” bacteria that are resistant to our available antibiotics.

For example, the go-to antibiotics for UTIs- Bactrim and Cipro- have become useless against UTI superbugs.

  1. We use too many antibiotics for UTIs, which has caused an increase in multidrug-resistant bacteria or “superbugs”.
  2. We need more accurate tests that tell us the right antibiotics for UTIs.
  3. Existing and new technologies need to simplify urine testing so that we can diagnose UTIs more quickly.  
  4. A new technology (biosensor-microfluidics) has the best potential for effective urine testing because they will be able to test urine directly in a small and portable device.
  5. These emerging technologies are our best bet for preventing “superbugs”.

To decrease the spread of superbugs and improve UTI treatments, scientist and doctors are using new and existing technology to target antibiotics to the genetic and molecular detail of UTI causing bugs. 

Ideally, a future antibiotic treatment will take into account our whole bacterial ecosystem, and will search the individual’s microbiome to choose the best antibiotic for them.

Available UTI Testing Options Are Not Ideal

  1. Urine dipstick, fast but often inaccurate screening tool (takes less than 2 minutes).
  2. Urine culture for detecting bacteria by growing them in culture, then using a regional database of antibiotics effectiveness (antibiogram) to suggest a “best guess” antibiotic (this takes at least 24 hours).
  3. More precise susceptibility testing where bacteria are grown with antibiotics to see if they slow down growth or kill the bacteria (this takes about 2 days). Your doctor then calls you to tell you the correct antibiotic to take, changing it if the original “best guess” antibiotics were wrong.

This system risks promoting superbugs because the “best guess” antibiotics may not be the right choice, exposing the bacteria to multiple antibiotics, and allowing them to develop resistance to our available antibiotics.

Moreover, this approach delays treatment, increasing our chance of getting a complicated UTI such as a kidney infection or sepsis.

That’s why new technologies that speed up diagnosis and accuracy are so important.

New Emerging UTI Testing Options

The ideal UTI testing is easy to use, cost-effective, and available either at your doctor’s office or even in your own home.  Below is a list of the up and coming tests that go beyond urine dipstick and cultures.

Screening tests for UTI-causing bacteria  

All UTI screening testing options (except the traditional dipstick) are only available through your doctor:

  1. Lateral flow immunoassays: urine is placed on a paper test,  giving you results in 5-30 minutes.
  2. Traditional dipstick urine test– quick and easy, but not always accurate.
  3. RapidBac– Sorry this one is only available for Fido and Tigger. It uses antibodies (similar to how we respond to vaccines) to detect UTI causing bugs. Studies are promising as it detects the most common UTI bugs, but scientists are not sure it is accurate enough yet for use in humans.
  4. Flow Cytometry: identifies cells (such as UTI causing bacteria) while they are passing through the apparatus and are illuminated with a laser beam. The light scatters when it hits the bacterial cell and the pattern could tell us what type the bacteria are. It takes about 45 minutes. They may be able to go a step further investigating which antibiotics work, by adding antibiotics to the urine and observing the change in the light’s behavior as bacterial composition changes after the interaction with antibiotics. Examples are: UroQuick (Alifax) and BacterioScan model 216 (BacterioScan Inc).

Advanced microbiology techniques to identify the DNA of UTI-causing bacteria

These tests are more specific than screening tests and are more appropriate for recurrent UTI testing.

Advanced microbiology tests identify UTI causing bacteria based on their genetic makeup, especially the modified genes that turn them into superbugs. These technologies are available, but are time intensive and require a lot of urine processing. Scientists’ goals are to make them more efficient than our current gold standard, the urine culture test.

  1. Next generation sequencing (NGS) by Aperiomics. This is a commercially available test that promises to “report all bacteria, DNA viruses, parasites and fungi identified along with the abundance of each”. This test takes about 1-2 weeks, not covered by insurance and will cost you several hundred dollars. Before ordering this test, make sure that your provider knows how to work with the results of NGS testing. While it might present more information, it is not clear just yet if practitioners know what to do about it.
  2. MALDI-TOF mass spectrometry this is bacteria fingerprinting; once the bacteria are isolated from the urine, its “fingerprint” is compared to a large database of bacteria fingerprints. We are able to get the urine processing down to about 3 hours with a sensitivity between 67-86%. The initial cost of the machine is quite high, so it is only available in large laboratories. Its current drawbacks are:
    • It requires a lot of urine processing.
    • Does not tell us the right antibiotic.
    • Can’t diagnose a UTI caused by more than one bacteria.
    • Expensive equipment.
  3. FISH- This test recognizes a piece of nucleic acid (such as DNA or RNA that is found in all living cells) that is unique to each bacteria. Currently, FISH tests are available for blood infections and can take as little as 20 minutes with good sensitivity and specificity (more than 96%). However:
    • It can’t yet tell us which antibiotics to use.
    • Is not easily integrated into your average doctor’s office.
    • Unfortunately, this test is not yet available for urine.
  4. Multiplex PCR– this test multiplies the nucleic acids (DNA or RNA) of a particular bacteria, making it easy to identify. Current issue:
    • They are sensitive and specific but are not yet available for urine infections (only blood and stool samples).
    • They also aren’t able to measure the number of bacteria, an important part of diagnosis as this lets us determine a true infection and ignore small amounts of innocent bacteria from the vagina or urethra.
    • It also doesn’t test for the right antibiotics.
  5. GeneXpert– not yet approved for UTI testing, but it can diagnose STDs (chlamydia and gonorrhea) from urine samples with sensitivity and specificity greater than 97%.
  6. SeptiFast– currently used for blood infections only, but studies in urine are promising.
  7. FilmArray– currently used for blood and stool samples, its sensitivity is more than 90%. It could be easily adapted to urine samples.

Susceptibility testing to identify best UTI treatment options

These tests determine which antibiotic will work best for your UTI, an important piece in treating you and limiting superbugs. Traditionally, this took two days as doctors wait for bacteria to grow (or die) when mixed with antibiotics.

New technologies speed this up quite a bit by using time-lapse photos that look at bacterial cell division (rather than growth). With this method, antibiotic susceptibility can be determined in under 2 hours!

  1. oCelloScope– a portable test kit that monitors bacterial growth when exposed to antibiotics. Its results are similar to traditional urine cultures but are still in testing stages.
  2. Accelerate ID/AST– this test identifies bacteria in 1.5 hours and determines the right antibiotics in under 5 hours. It has been studied in blood, urine and sputum samples, but has is not yet integrated into clinical labs for widespread use.  

Emerging UTI testing research trends

Needless to say, there is a lot of space for improvement in UTI testing industry. The goal is to get tests that:

  • Differentiate between infection and non-infection (like interstitial cystitis),
  • And are quick (less than 3 hours).

We need to improve the accuracy, accessibility, and efficiency of testing. Here are two most important UTI testing trends to follow:

  • Biosensors: these are tiny tools that are quick and sensitive and are able to produce a signal (like fluorescence) after identifying a piece of the bacteria (like its DNA). This alerts scientist to the specific type of bacteria as well as their numbers.
  • Microfluidics is the study of very small (micron level) amounts of fluid.

Both of these technologies are small, portable and can work as an add-on to smartphone technology, which could be really convenient. They also use little energy. An important concept is that you can sample urine directly rather than waiting days for the bacteria to grow in culture. This saves a lot of time.

Here are examples of biosensor and microfluidic technology that are on the horizon:
  1. eNose: this is a handheld system that detects volatile organic compounds (odors). Studies show that the eNose’s ability can detect bacterial odors in 15 minutes and is just as accurate as the traditional urine culture.
  2. Electrochemical biosensors– this test detects UTI-causing bugs by targeting unique nucleic acid of the bacteria and recognizing it with a complementary DNA. Studies show it can determine the type of bacteria, its number and the best antibiotic for treatment in under five hours and is very accurate. It is versatile as it identifies urinary parasites (which cause UTIs in endemic areas like East Africa) and recognizes proteins as well as DNA (which might make it both a screening and diagnosing test).

Biosensors and microfluidics are really promising as UTI tests because they are accurate and fast. Still, they are in their infancy and not yet commercially available. The scientists must work to make these technologies easier for doctors and laboratories to use. Initially, they will likely be restricted to people with complicated UTIs, before becoming more widely available.

Will Better UTI Testing Solve Recurrent UTIs?

Many researchers point out that healthy bladders might have similar microbiome to the bladders of patients who suffer from recurrent UTIs. Therefore we must move past a system that only looks for more potent antibiotics that may harm our natural microbiome.

More information appears that some bacteria such as BV inducing Gardnerella vaginalis could provoke dormant E.coli bacteria for an acute infection. So if you only target bacteria within the bladder, you could be missing a point.

Better diagnostic requires a deeper understanding of how our bodies work together with our microbial communities. We can’t keep on blasting all bacteria with yet better, more precise antibiotics and hoping that this will solve the issue. If you think about your body and organs as an integrated reservoir with streams flowing in both directions, you will approach your healing differently.

We can hope that the future tests will be more precise, cheaper, and faster. We should also ask that the practitioners of medicine provide a more holistic approach that takes into account all the possible causes and solutions to treating potentially pathogenic bacteria. 

References:

  1. Cussans A, Somani BK, Basarab A et al. The role of targeted prophylactic antimicrobial therapy before transrectal ultrasonography-guided prostate biopsy in reducing infection rates: a systematic review. BJU Int. 2016 May;117(5):725-31.
  2. Davenport M, Mach K, Shortliffe L et al. New and developing diagnostic technologies for urinary tract infections. Nat Rev Urol. 2017 May; 14(5): 296–310.
  3. Koczula K, Gallota A. Lateral flow assays. Essays Biochem. 2016 Jun 30; 60(1): 111–120.
  4. Roine A, Saviauk T, Kumpulainen P et al. Rapid and accurate detection of urinary pathogens by mobile IMS-based electronic nose: a proof-of-principle study. PLoS One. 2014 Dec 19;9(12):e114279.

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