Urine is never Sterile
A former myth that bladder was sterile was confirmed by Pasteur in 1881. He sealed a vial of urine in a container, and it didnâ€™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 itsâ€™ 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 didnâ€™t grow anything, but E. coli and other fast-growing bacteria, thus making urine sample with other types â€˜sterileâ€™.
The bladder is sterile, and urinary tract infection starts with invasion by a pathogen from an outside sourceâ€”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 â€˜urine is not sterileâ€™. 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 35â€“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 â€˜The Bladder is Not Sterile: An Update on the Urinary Microbiomeâ€™ addresses these issues well. This is a must-read article.
There is another article by Aram Kim, Hyeong Gon Kim* et al (2021 published online) on â€˜What is the Cause of Recurrent Urinary Tract Infection? Contemporary Microscopic Concepts of Pathophysiologyâ€™ is also a must read to gain additional knowledge on why Urine is not sterile.
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,