“I feel like I’ve got a urinary tract infection… but my doctor says I can’t because my tests are negative”

Many chronic urinary tract infection (UTI) sufferers have had their symptoms dismissed by their GP or urologist on the basis of dipstick tests and mid-stream urine (MSU) cultures. Worryingly, these tests are seriously flawed.

  • Standard mid stream urine (MSU) cultures miss 90% of chronic urinary tract infections
  • Dipstick analysis (leucocyte esterase test) miss at least 60% of chronic urinary tract infections.

Just because your tests doesn’t find evidence of an infection, this is not evidence that you don’t have a UTI.

How do doctors diagnose urinary tract infection?

Diagnosis for a urinary infection is usually done in the GP surgery or a walk-in clinic. After you explain your symptoms,
a mid-stream urine sample is taken and a dipstick test is carried out to check for:

  • White blood cells – Also known as leucocytes, the presence of white blood cells This indicates that there is inflammation or infection in the urinary tract or kidneys and the body is excreting more white blood cells to destroy any possible bacterial infection.
  • Red blood cells – The bladder can bleed due to severe inflammation and the constant urination caused by a UTI. Some people can feel a “razor blade sensation” when urinating during a UTI attack.
  • Protein – The presence of protein can indicate a possible kidney infection as only trace amounts normally filter through the
    kidneys.
  • Nitrates – Gram-negative bacteria like e-coli, which can cause a UTI, make an enzyme that changes waste urinary nitrates to
    nitrites.

Any sign of these in the urine indicates bladder inflammation and a probable infection as the body’s immune system is reacting to the infection, but could also indicate other conditions.

Depending on the dipstick analysis, the GP may send the sample to a laboratory where they culture the urine for bacterial growth. The GP will discuss your symptoms with you, taking into account other current or previous health issues and any family disease history.

Negative test results

Unfortunately both dipstick test and the mid-stream urine culture test aren’t reliable and miss infections. There are several reasons for this:

Diagnostic criteria for UTI is based on outdated research

The use of MSUs and dipstick tests to diagnose UTIs are based on research by a scientist called Kass from the 1950s based on a study of a small number of pregnant women suffering from severe infections of the kidneys. These women, who were not suffering from lower urinary tract infections, are not representative of the typical UTI sufferer.

  • The current microbiological criteria to diagnose UTI, called the Kass Criteria, is set very high, meaning that levels of infection under this threshold are discounted. The Kass criteria threshold looks for at least 105 (100,000) bacteria per millilitre of urine of a single species of a known pathogen. But UTI symptoms can be caused by low levels of pathogens and caused by more than one pathogen.
  • The Kass criteria assumes that the bladder is sterile and a mixed growth results is likely to be a contamated test. But we now know that the bladder is not sterile  The urinary microbiome is complex and a normal bladder hosts up to 400 different species of organisms.

Test miss bacteria that cause infections

  • Culture tests are insensitive and miss many pathogens that cause infection – it favours fast-growing bacteria, like e-coli, and is unable to culture slow-growing bacteria orpathogens that die on contact with oxygen. The culture test detects as little as 12% of other clinically significant species that can cause infections. 1
  • The dipstick test only looks for the presence of gram-negative bacteria, as e-coli, ignoring other possible pathogens that cause infections.
  • The dipstick detects the nitrites which are produced by gram-negative bacteria and white blood cells, produced when the body is fighting an infection. But even then the dipstick test misses infections; Positive for nitrite in less than 18% of UTIs and positive for leucocytes in less than 40% of acute UTIs with a positive MSU culture. 2,3,4
  • The dipstick and culture test do not detect bacteria that are dormant and embedded in the bladder wall, so they fail to detect embedded, chronic infections. Dipstick test fail to detect 40% of chronic infections. The MSU test fails to detect 90% of chronic infections. 2,3

New research missing from diagnosis

New research studies show that:

  • A healthy bladder is not sterile. Just like the gut, the bladder has its own balance of good and bad bacteria called the ‘urinary biome’. Our bladder contains about 500 different types of bacteria which usually coexist happily.
  • There is no evidence that UTIs are caused by a single type of bacteria and multiple studies suggest that multi bacterial infections are common. A healthy bladder has a balance of hundreds of different strains of bacteria which are more or less sensitive to different types of antibiotics. An antibiotic that wipes out all or most of one type of bacteria can allow numbers of another strain to rocket. The second strain of bacteria, which might not have been a problem when there was just a few of them, now becomes an infection.
  • Some strains of bacteria are easier to culture – they grow easily in the laboratory. Other strains divide too slowly to show up in the usual length of time given and they can be ‘crowded out’ by stronger, fast-growing types. Some types of bacteria die in the presence of oxygen so cannot be grown in a laboratory.
  • Research shows that epithelial cells are found in greater numbers in the urine of chronic UTI sufferers. The wall of the bladder and urethra is made up of urothelial cells about five layers deep. As an infection advances, bacteria move from the urine into the cells. The body’s immune system responds to the infected cells by shedding them. At this point, bacteria that have been living inside the cell burst back out into the urine and the infection flares up again.

What is the most reliable way to diagnose chronic UTI?

Relying on inaccurate tests sees many thousands of UTI sufferers misdiagnosed or even dismissed as ‘problem patients’.

Unhelpfully guidelines from the National Institute for Health and Care Excellence (NICE) – the body that produces treatment guidelines for England and Wales – insist that a positive dipstick and MSU are needed to diagnose a urinary tract infection in patients who have not got better after initial antibiotics.

The most useful thing that doctors can do is to listen to their patients and ask them detailed questions about their symptoms and how they started.

New research suggests that microscopy – analysing fresh urine under a microscope using a haemocytometer (a device used to count white blood cells and epithelial cells) – combined with listening to a patient’s story is the best way to diagnose UTI.

I think I have chronic UTI

References:
1. Price, T. K., Dune, T., Hilt, E. E., Thomas-White, K. J., Kliethermes, S., Brincat, C., Brubaker, L., Wolfe, A. J., Mueller, E. R., Schreckenberger, P. C.
(2016). The clinical urine culture: enhanced techniques improve detection of clinically relevant microorganisms. Journal of Clinical Microbiology, 54(5), 1216-
1222.
2. Sathiananthamoorthy, S., Malone-Lee, J., Gill, K., Tymon, A., Nguyen, T.K., Gurung, S., Collins, L., Kupelian, A. S., Swamy, S., Khasriya, R.,
Spratt, D.A., Rohn, J. (2019). Reassessment of routine midstream culture in
diagnosis of urinary tract infection. Journal of Clinical Microbiology, 57(3), e01452-18.
3. Gill, K., Kang, R., Sathiananthamoorthy, S., Khasriya, R., Malone-Lee, J. (2018). A blinded observational cohort study of the microbiological
ecology associated with pyuria and overactive bladder symptoms.
International Urogynecology Journal, 29(10), 1493-1500.
4. Khasriya, R., Malone-Lee, J. (2010). The inadequacy of urinary dipstick and microscopy as surrogate markers of urinary tract infection in
urological outpatients with lower urinary tract symptoms without acute frequency and dysuria. Journal of Urology, 183(5), 1843–1847.
5. Stamm, W.E., Counts, G. W., Running, K. R., Fihn, S., Turck, M., Holmes, K.K. (1982). Diagnosis of coliform infection in acutely dysuric women.
New England Journal of Medicine, 307(8), 463-468.