Urine is never Sterile

• 30 May 2021 10:04:06 AM
• |General Urology

Dear All,

A former myth that bladder was sterile was confirmed by Pasteur in 1881. He sealed a vial of urine in a container, and it didn’t turn cloudy, thus it was considered free from bacteria. This logic assumed that urinary bacteria grow in aerobic conditions, but it was found that most do not. In 1950s, Kass developed the standard urine culture protocol, which was very successful due to its’ ability to effectively detect E. coli, the most common source of pyelonephritis.  This test was later applied to bladder infections. However, standard urine culture protocol didn’t grow anything, but E. coli and other fast-growing bacteria, thus making urine sample with other types ‘sterile’.

The bladder is sterile, and urinary tract infection starts with invasion by a pathogen from an outside source—this common belief derives from the fact that the verdict of negative urine culture (<10³CFU/ml) results when no growth is observed on the culture plate. However, under different culture conditions, the same urine does yield colonies, leading to the conclusion that ‘urine is not sterile’. At minimum, the bladder contains a microbiome that consists mainly of species that never cause urinary tract infection (UTI) but can include potential UTI causes.

This idea challenges the concept that a UTI always starts with invasion of the urinary tract. A UTI may also start from a microbiome that is given the chance to multiply. With a doubling time of approximately 60 min, multiplication may proceed rapidly. A bladder microbiome might explain the association between residual urine after voiding, delayed voiding, and vesicoureteral reflux and cystitis or nephritis. Why would reflux of sterile urine increase the chance for nephritis? The presence of a bladder microbiome also sheds a light on UTI recurrence. For women in whom an uncomplicated Escherichia coli UTI was successfully treated with a 7-d course of Antimicrobials  (negative culture at day 10), the strain that caused a new E coli UTI within 35–49 d proved to be identical to the original infecting strain in 77% of all cases. The E coli appears to survive the treatment using mechanisms such as Biofilm formation.

The message for urologists who treat patients with recurrent UTI is that a negative urine culture indicates the cure of the ongoing UTI but not removal of the risk of recurrence. The patient most likely still carries the pathogen inside the urinary tract and may develop a new UTI when the microbiome is given the chance to multiply. Prevention of a UTI will require more emphasis on prevention of residual urine, delayed voiding, and vesicoureteral reflux, as well as the development of interventions that attack the survival mechanisms of the pathogen.

The fact that Urinary Microbiome can paly a role in many disorders of Urinary Tract is leading us to understand the genesis of these diseases.

The article by A Lenore Ackerman and Toby C. Chai* (2019) on ‘The Bladder is Not Sterile: An Update on the Urinary Microbiome’ addresses these issues well. This is a must-read article.

https://link.springer.com/content/pdf/10.1007/s11884-019-00543-6.pdf

There is another article by Aram Kim, Hyeong Gon Kim* et al (2021 published online) on ‘What is the Cause of Recurrent Urinary Tract Infection? Contemporary Microscopic Concepts of Pathophysiology’ is also a must read to gain additional knowledge on why Urine is not sterile.

https://www.einj.org/upload/pdf/inj-2040472-236.pdf

With all these facts under our belt now, many questions remain. What roles do detected bacteria play: which ones are beneficial? Which ones detrimental? How do they interact with each other and the host? What about non-bacterial microbes? How stable/resilient is the Microbiome? When does it become established? Does it change with life events?

It appears that we are beginning to understand the tip of the iceberg and will have to go long way still.

With warm Regards,

Venu

Comments(3)

• 

  Dr G G Laxman Prabhu

  30 May 2021 05:24:55 PM

  Let us respect the ultramicrocosm

  
  

  It is hard to conceive for a questioning mind that urinary tract which opens into the exterior like the GI tract to be absolutely sterile! The role played by the GI  and vaginal microbiota in preserving and maintaining the health of the host is now clearly documented. The existence of similar microbes and their role in health of the urinary tract is being increasingly recognized. The human has a trillion cells  which are not its own, supporting it. We owe our health to these. While the human is a microcosm in a macrocosm, the microbes with in us is an ultramicrocosm!

  These invisible friends of the human being perhaps are lost from service for various reasons- aging and disease, none more disastrous than indiscriminate use of broad spectrum antimicrobials.

  Better understanding of their role in preventing pathogenic microbes from invading the urinary tract, their biosynthetic functions and the role of protection from cancer will make them earn more respect.

  Let us not shoot our own feet while using antimicrobials now onwards. Short course of a narrow spectrum antibiotic which works at least inhibitory concentration should be the approach while dealing with infections. 

  
  

  Dr G G Laxman Prabhu

  
  

  
  

• 

  Dr. Roy Chally

  30 May 2021 10:11:39 PM

  Could not unload the original article in the first link. The summary is raising many questions

  Read the full article in the second link

  Comments and some doubts. 

  1. In symptomatic UTI a CFU of 10 to the power of five and above in culture is diagnostic. 

  2. The lower limit of CFU which can cause symptomatic not known. 

  3. The extended or enhanced, quantitative urine culture is a new tool for the diagnosis UTI in symptomatic patients. The positive culture goes up by another 20% above the standard urine culture with this technique in symptomatic patients. 

  4. Studies on Microbiome in GI tract and vagina are revealing many new significant insights in health and disease. 

  GI microbiome changes with antibiotics. GI microbiome has a role in UTI. 

  5. New studies show that bacteria can survive in intercellular environment by forming a biofilm inside the cell. New studies show that they can multiply within the cells. It is postulated that this could be a reason for recurrent infection.   Will this happen with normal immune system. What is the evidence for this? We were taught that the bacteria are engulfed by the macrophage. 

  6 Like in G I Tract new studies reveal that bladder has a Microbiome in normal asymptomatic individuals. 

  7 Evidence for this comes from 16S rRNA gene sequencing of Urine. In other words this is the proof of bacterial DNA and bacteria in bladder. This technique r RNA sequencing of urine could also yield information on bacterial resistance. 

  8. A large variety  rRNA are isolated. Some known urinary and some unknown pathogens. 

  9. The role of these urinary “bladder” bacteria ( r RNA) in health and disease is a subject for intense research. The postulations that they can cause Urge incontinence, reflux etc are not conclusively proved 

  10. My doubt is whether they have excluded  that rRNA is not a product of filtration by glomeruli. 

  
  

  
  

• 

  Venugopal P

  01 Jun 2021 11:35:56 AM

  Dear All,

  Roy in his commentary on the Post mentioned that he could not open the first link provided and restricted to commenting on 2^nd link. I am sure the subject being new, many will have reservations in accepting the thought that bladder can never be sterile. It has ben studied and proved that Urinary Microbes could be responsible in many Urological conditions as mentioned and reasoned out in this article (PDF Provided).

  With warm Regards,

  Venu

   

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