How Are UTIs Diagnosed? Urinalysis, Urine Culture, PCR, and Advanced Testing Explained

Urinary tract infections (UTIs) are the most common outpatient infection globally. Caused by bacteria or fungi in the urinary tract, which includes the urethra, bladder, ureters, and kidneys, UTIs can manifest in a variety of symptoms that range in severity. Sometimes other conditions can mimic urinary tract infection symptoms, making the clinical diagnosis of UTIs particularly important. But how do doctors actually diagnose UTIs?

The Current Standard of Care

Urinary tract infection is a clinical diagnosis that takes into account a patient's current symptoms, medical history, as well as laboratory findings. It begins with your doctor taking a patient history – that is, asking you questions about what symptoms you are experiencing, when they began, if you have had UTIs previously, and other questions to understand your risk for UTIs. Following this, your doctor will likely order two types of tests to confirm an infection, both of which will require a urine sample. These tests are called a urinalysis and potentially a urine culture.

Urinalysis is a test with a quick turnaround time that evaluates your urine across three levels of analysis:

Macroscopic exam -- a visual inspection of your urine sample, assessing color, clarity, and odor for signs of infection or other abnormalities.

Dipstick chemical analysis -- a thin test strip is placed into your urine sample to detect chemical markers. For UTI diagnosis, the most relevant include:

• Leukocyte esterase: an enzyme released by white blood cells; a positive result suggests your immune system may be responding to infection in the urinary tract
• Nitrites: some bacteria convert nitrates naturally present in urine into nitrites; a positive result suggests bacterial infection, though a negative result does not rule one out, since several common UTI-causing bacteria do not produce nitrites
• Blood: can accompany infection when tissues in the urinary tract are damaged by a pathogen, but is not specific to UTI

Microscopic exam -- a laboratory technician examines your urine under a microscope, looking for white blood cells, red blood cells, bacteria, and other cellular material. The presence of elevated white blood cells (called pyuria) is one of the stronger indicators of a urinary tract infection and provides more definitive information than the dipstick alone.

Urine culture is a test that takes several days and is often performed in a laboratory outside of the clinic. This test attempts to grow the bacteria or fungi that is present in your urine on a petri dish. The bacteria or fungus that grows is compared to a clinical threshold called colony-forming units (CFUs) to determine whether or not it is truly an infection. Additional testing can be done to help determine which antibiotic to use to treat the infection, which similarly takes several days to complete. Your doctor will take your medical history, urinalysis, and urine culture results into account in order to confirm that you have a urinary tract infection and provide the proper treatment for it.

Limitations to the Standard of Care

Despite continuing to be the standard of care, urinalysis and urine culture often miss the mark in accurately diagnosing urinary tract infections. In fact, as many as 1 in 3 cases are missed by urine culture, making this quite a problem. These cases are called culture-negative UTIs.

Because urine culture attempts to grow the pathogen from a urine sample on a petri dish, it is prone to a variety of issues. Some reasons as to why a urine culture might fail include

• The pathogen causing a UTI does not have the proper conditions or nutrients to grow.
• Some bacteria and fungi may grow too slowly to be reported by the laboratory.
• The amount of bacteria or fungus detected could be below the clinical threshold, and thus not reported, despite it being the cause of UTI symptoms

Increasingly, doctors are realizing these limitations and the need for new diagnostic tests that are more accurate. These approaches focus on detecting the DNA of the bacteria or fungi causing a UTI rather than trying to grow them from a urine sample.

Polymerase-Chain Reaction for UTI

Polymerase-chain reaction, more commonly known as "PCR," is one type of laboratory technique being used to diagnose UTIs. This technique looks for fragments of DNA that are specific to different bacteria and fungi. If present in a urine sample, these fragments of DNA are copied over and over again. When enough copies are made, the bacteria or fungi is considered present in the urine sample, and a diagnosis is made.

This technique has both benefits and shortcomings in comparison to urine culture. The benefits of using PCR include:

• Faster turnaround time (often within 24 hours)
• Higher sensitivity than urine culture
• Can identify antibiotic resistance genes

There are also drawbacks to this technique in comparison to urine culture. First, because PCR is considered a "targeted" technique, if a bacterium or fungus is not included in the test, then it will not be detected. PCR tests for UTI often only include the most common UTI-causing pathogens, which means that atypical bacteria or fungi that can cause a UTI may be missed. Secondly, because it is much more sensitive than urine culture, PCR tests can sometimes detect bacteria or fungi that exist in the urinary tract that are not the true cause of the infection. Doctors need to pay careful attention to the test results and symptoms to determine whether the bacteria or fungi detected are indeed the likely culprit.

Next-generation sequencing for UTI

The other technique increasingly being used to diagnose urinary tract infections is called next-generation sequencing. Similar to PCR, this test looks for pathogen DNA in a urine sample. But rather than looking for specific bacteria or fungi, this test makes copies of all of the DNA in a urine sample and determines the "sequence" of these. This sequencing data is then compared to a database of microorganisms to determine which ones were present in the urine sample.

This type of testing has many advantages over both PCR and urine culture. Because it does not look at specific bacteria or fungi, but rather all of them in the sample, it is able to identify atypical pathogens that cause UTIs as well as pathogens that are difficult to grow. Additionally, tests that use next-generation sequencing are able to identify key traits about the pathogens detected, such as antibiotic resistance markers, virulence factors, or particularly worrisome strains of bacteria or fungi that require careful treatment. Higher sensitivity, more comprehensive results, and a similar – if not faster – turnaround time as urine culture make next-generation sequencing-based UTI tests a powerful new tool for doctors and patients alike.

Biotia has developed a next-generation sequencing-based diagnostic test for urinary tract infections that is now directly available to patients suffering from recurrent, complicated, and/or culture-negative urinary tract infections. Called the BIOTIA-ID Urine Test, this test identifies 40+ key urogenital pathogens, including ones often missed by urine culture or excluded from PCR panels. The BIOTIA-ID Urine Test additionally provides doctors with information about antibiotic resistance markers to help guide precision treatment. Additional pathogens, resistance markers, and virulence factors are currently undergoing rigorous clinical validation to add more value to patients and doctors alike. By testing with Biotia, patients experiencing UTI symptoms will also get connected to our partner telehealth providers at Clinova.Solutions, a healthcare practice that focuses on recurrent and complicated urogenital infections and other urinary health issues.

The major drawback to next-generation sequencing tests for UTI, paradoxically, is their novelty. Newer technology is slow to be adopted by regulatory authorities and insurers. Much more comprehensive research and development work is required to demonstrate their performance, which increases their cost. However, as this technology grows in popularity, it is expected that insurers will begin to cover these types of tests, increasing access for patients in need.

Is the BIOTIA-ID Urine Test Right For You?

If you are experiencing recurrent UTIs, culture-negative UTI symptoms, or infections that haven't responded to standard antibiotic treatment, the BIOTIA-ID Urine Test may provide the answers your current tests have missed. By identifying 40+ urogenital pathogens and antibiotic resistance markers through next-generation sequencing, the BIOTIA-ID Urine Test can help give you and your doctor a more complete picture — so treatment can be targeted from the start. Learn more about who it is for.