What is Chronic UTI? - Chronic UTI Australia
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What is Chronic UTI?

There is very little mainstream awareness or knowledge about chronic UTI. It is unlikely doctors will consider chronic UTI as a possible cause for those with ongoing lower urinary tract symptoms (LUTS) who return negative results on mid-stream urine (MSU) cultures and urinary dipsticks.

How UTI is defined

A urinary tract infection (UTI), also known as cystitis, bladder infection, water infection, kidney infection or pyelonephritis, is an infection occurring anywhere in the urinary tractfrom the kidneys to the urethra.  A lower UTI involves the bladder and anything below, like the urethra and prostate.  An upper UTI involves the urinary system above the bladder, such as the ureters and kidneys (pyelonephritis).

 

A UTI is routinely diagnosed by a doctor who tests your urine sample for signs of infection with a dipstick at the clinic, and/or sends a sample to a clinical lab to test for bacteria.  You can read much more about UTI testing here.

 

People with more than two positive UTIs in six months, or more than three positive UTIs in one year, are generally diagnosed as having recurrent UTIs.   People with ongoing or intermittent UTI symptoms and negative test results are commonly diagnosed with a urinary syndrome, such as interstitial cystitis/painful bladder syndrome (IC/PBS).  People with UTI symptoms and a mix of positive and negative UTI test results can fall somewhere in between.

 

Based on new research, including newly discovered mechanisms of microbial behaviour within the bladder, we believe many of these people may be suffering from a chronic UTI.

 

Once a UTI has progressed into a chronic form, it is hard to diagnose and can become very complicated to treat. Not surprisingly, the sooner a chronic UTI is diagnosed and treatment begins, the easier it is to treat and the sooner it will resolve.  The issue is, there are currently no tests or treatment guidelines for chronic UTI in Australia. Not all doctors recognise chronic UTI as a disease or know how to treat it.  This is often where the problems begin for so many.

The difference between acute UTI and chronic UTI

 

 

 

Acute UTI

To understand chronic UTI, it helps to know a bit about acute UTI.

 

During an acute UTI, pathogenic bacteria will invade the urethra/bladder and multiply aggressively and rapidly in the urine. This is known as a planktonic infection.  Symptoms of an acute UTI can include excruciating bladder/lower abdominal pain, painful urination (dysuria), urgency, extreme frequency, lower back pain and sometimes cloudy, smelly or even blood-filled urine. If left untreated, the bacteria invading the bladder can ascend and colonise the kidneys. In the worst case, bacteria can then enter the blood stream resulting in life-threatening septic shock.

 

For about 70 percent of people with acute UTI, a short-course of antibiotics will quickly resolve the infection. For the remainder who do not respond properly, complications begin.

 

Armando Hasudungan provides a good video description showing how acute UTI develops.

Chronic UTI

Chronic UTI can be the result of an improperly treated acute UTI. For example, chronic UTIs can occur when test-positive infections do not fully resolve after a standard course of antibiotics (which researchers say happens to between 25–35 percent of people1). Chronic UTIs can also be the result of being prescribed the wrong antibiotics or not receiving antibiotic treatment soon enough—or not at all.

 

 

Bacteria can invade cells in the bladder wall

An improperly treated UTI can lead to intracellular bacteria burrowing into the bladder and/or urethral lining (uroepithelium) where they safely hide away from further immune or antibiotic attack6 .

 

The bladder wall is usually around five to six cells deep and the bacteria have been shown to burrow down at each layer. Once inside, they hide in the spaces and fluid between cells (interstices and interstitial fluid) or they can invade the cells.  This is referred to intracellular colonisation.

 

Leading research from the US3 and the UK4 has shown that bacteria, such as E. coli, have the ability to invade the cells lining the bladder wall very early on during an acute infection. There they can remain dormant for lengthy periods to avoid attack. Safely inside the bladder wall, the bacteria carry on with their mission to survive, divide and thrive, and will do so at various opportunities and intervals.  For example, when the conditions are optimal, the bacteria take advantage and burst out of the cells and proliferate very rapidly in the urine in the bladder.  This is often described as an ‘acute’ infection.

 

 

Bacteria can form biofilms

These clever bacteria have also evolved with the ability to form a biofilm—which is a natural, sticky coating that holds the bacteria closely together and protects them from harm. Bacterial biofilm can be multi-microbial (this means they can contain many different pathogens and species).  They can form on the surface of the bladder wall as well as inside the bladder wall cells3, 4. Biofilm infections are a relatively new discovery and are estimated to be associated with around 80 percent of human bacterial infections2. Traditional UTI culturing methods are not designed to look for biofilm or intracellular infections, so it is important to question if these tests are fit for purpose. (There is more on biofilms further down the page.)

 

 

The immune system fights back

Things become complicated when the cells of the bladder wall recognise the invasion and send signals (via cytokine signalling pathways) to launch an immune attack. As with all infections, this results in an inflammatory response as white blood cells answer the call to action. However, the white blood cells cannot find the invaders because they are cleverly hidden within the cells or covered by their protective biofilm shield. The white blood cells are not able to complete their mission and the whole immune response results in unpleasant symptoms from this on-going battle within the bladder.  Please click here to learn more about the disease process.

 

 

Lower cell numbers do not meet diagnostic criteria

Unlike an acute infection that involves large numbers of rapidly thriving and dividing bacteria bubbling away furiously in the urine, a chronic infection involves much lower numbers of bacteria that have stuck firmly to the surface or are inside the cells.  Subsequently, there will be lower numbers of white blood cells that usually do not meet the diagnostic thresholds applied for acute UTI. Low diagnostic numbers commonly associated with chronic UTI usually fly under the radar when it comes to microscopy, MSU cultures or urinary dipstick testing methods.

 

 

Symptoms continue as undetected bacterial infection continues to fester

The cells of the bladder wall shed naturally about every 100 days. When it is time for infected cells to shed, the bacteria sense their impending doom and jump into action. They vigorously multiply and break out of the dying cells so they can seek fresh, new uninfected cells to live in/on.   This is described as a ‘planktonic flare’ which results in increased bacterial activity that overwhelms the body’s immune response, causing on onset of acute symptoms. Sometimes at this stage, white blood cells or bacterial numbers could achieve acceptable diagnostic thresholds and this is usually mistaken as a ‘new’ UTI. Low levels of white blood cells, epithelial cell shedding and planktonic bacteria from a chronic UTI are unlikely to satisfy these thresholds, which were only ever designed to diagnose acute pyelonephritis5 (a kidney infection)—a much more severe and serious form of infection. You can read more about UTI testing here.

 

 

– CLICK HERE TO LEARN  MORE ABOUT HOW CHRONIC UTI FORMS –

 

Biofilm basics

To help understand biofilm bacterial infections, you can watch the following Youtube videos.

The late Dr Bill Costerton (the Father of Biofilms) explains biofilm in this 2012 interview.

This short video helps further explain the process of biofilm formation.

  1. Milo, G., et al., Duration of antibacterial treatment for uncomplicated urinary tract infection in women. Cochrane Database Syst Rev, 2005(2): p. CD004682.

 

  1. U. Römling and C. Balsalobre, Biofilm infections, their resilience to therapy and innovative treatment strategies, Journal of Internal Medicine, vol. 272, no. 6, pp. 541–561, 2012. http://onlinelibrary.wiley.com/doi/10.1111/joim.12004/full

 

  1. Justice, S.S., et al, Differentiation and deevelopmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis, PNAS, 2004, vol. 101, no. 5, pp 1333–1338  pnas.org/content/101/5/1333.full.pdf

 

  1. Horsley, H., et at, Enterococcus faecalis Subverts and Invades the Host Urothelium in Patients with Chronic Urinary Tract Infection, 2013 Dec, PLOS One, http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083637

 

  1. Khasriya R & Malone-Lee J: 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. J Urol. 2010 May; 183 (5): 1843–7.

 

  1. Hultgren et al: Effect of trimethoprim-sulfamethoxazole on recurrent bacteriuria and bacterial persistence in mice infected with uropathogenic Escherichia coli, IAI 2002 Dec;70(12):7042-9, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC132990/

 

– Learn How Chronic UTI Forms Here –

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