Regular micturition, the physical barrier provided by urothelial cells and mucin, and the immune system usually prevent bacteria from colonising the urethra and, in turn, the bladder (Gaston et al, 2021). Catheterisation can undermine these defences and may lead to urinary tract infections (UTIs) (Gaston et al, 2021). On average, between 3–10% of people with a catheter develop bacteriuria each day (Shuman and Chenoweth, 2018). Biofilms are central to the development of catheter-related UTIs.
Biofilms and UTIs
Inserting a catheter can damage the urothelial barrier and trigger immune responses. As a result, the patient may deposit proteins (eg fibrinogen) onto the catheter surface (Gaston et al, 2021). Moreover, inserting a catheter can disrupt micturition. Therefore, patients may retain urine in the bladder, which facilitates microbial growth (Gaston et al, 2021). The flow of warm urine, which is nutrient rich, means that free-floating bacteria attach to the catheter aided by the protein deposited on the tube's surface (Azevedo et al, 2014; 2017; Gaston et al, 2021).
The bacteria that attach to the catheter have various origins. For instance, microorganisms from the patient's intestinal tract and perineum can ascend the urethra, causing catheter-associated UTIs (Shuman and Chenoweth, 2018). A recent study of healthy premenopausal women reported ‘a large overlap’ between the urinary microbiome and microbial communities in the vagina and periurethral region (Biehl et al, 2022). In addition, bacteria transmitted between patients can cause some catheter-associated UTIs, such as among hospital in-patients (Shuman and Chenoweth, 2018).
The free-floating bacteria that attach to the catheter start producing extracellular matrix (ECM), which consists of macromolecules such as proteins, polysaccharides and nucleic acids (Azevedo et al, 2017; Shuman and Chenoweth, 2018). The ECM stabilises and aids the development of the bacterial community on the catheter. Biofilms are clusters of microorganisms, embedded in a scaffold built from ECM. The meshwork-like ECM allows nutrients and oxygen to reach the embedded microorganisms (Azevedo et al, 2017). Biofilms can allow bacteria direct access to the bladder (Bossa et al, 2017; Shuman and Chenoweth, 2018).
Up to about 7 days of catheterisation, the biofilm tends to contain an single species (Azevedo et al, 2017). However, the ECM allows other bacteria to attach to and colonise the biofilm (Azevedo et al, 2014; Azevedo et al, 2017; Shuman and Chenoweth, 2018; Gaston et al, 2021). As a result, the bacterial profile changes as the duration of catheterisation lengthens. Indeed, biofilms contribute to colonisation of the catheter with pathogens that can be resistant to several antibiotics (Shuman and Chenoweth, 2018). Biofilms also protect bacteria from immune cells and antibodies (Azevedo et al, 2014; Shuman and Chenoweth, 2018). The ECM and the slower growth of microorganisms in biofilms often further reduces antibiotic effectiveness (Shuman and Chenoweth, 2018).
The urinary microbiome
As mentioned, microorganisms from the patient's intestinal tract, vagina, periurethral region and perineum can ascend the urethra and potentially cause catheter-associated UTIs (Shuman and Chenoweth, 2018; Biehl et al, 2022). However, there is another source of pathogens that can colonise the catheter.
Traditionally, health professionals regarded the urinary tract as sterile, unless there was a clinical infection (Karstens et al, 2016; Biehl et al, 2022). Microbiologists now know that the urinary tract harbours a community of bacteria, even in people with negative results on conventional cultures (Karstens et al, 2016).
In part, microbiological advances prompted the recognition of a urinary microbiome in the bladder of healthy women (Biehl et al, 2022). Genetic testing found, for instance, bacteria in the bladder of 68.6% of 51 pregnant women who underwent straight catheterisation or transurethral Foley catheter placement. The standard urine culture had a false negative rate of 100% and did not detect several known or emerging urinary pathogens (Jacobs et al, 2017).
The findings are of more than academic interest. Genetic analysis suggests that the urinary pathogens responsible for uncomplicated acute cystitis differ from those that cause recurrent cystitis (Yoo et al, 2021). One study reported that 10 women with urgency urinary incontinence showed statistically significant increases in levels of 14 bacteria compared with 10 women with normal bladder function. The less diverse the urinary microbiome, the more severe the symptoms of urinary incontinence (Karstens et al, 2016). A study that enrolled 49 men aged between 40 and 85 years reported that combining culture and genetic tests identified bacteria in catheterised urine from 22.2% who had mild lower urinary tract symptoms, 30.0% with moderate symptoms and 57.1% with severe symptoms (Bajic et al, 2020).
Monitoring the microbiome
Overall, the urinary tract shares 63% of bacterial species with the gut microbiome and 32% with the vagina (Perez-Carrasco et al, 2021). However, the urinary microbiome in a particular person is highly individual. A study of three catheterised neurogenic patients showed that each ‘had a community that was unique to the individual, and few organisms were shared’ between the patients (Bossa et al, 2017).
The composition of a particular person's urinary microbiome may change with, for example, age, menstruation and time since last sexual intercourse (Biehl et al, 2022, Gaston et al, 2021). In addition, some strains in the urinary microbiome can compete with and inhibit each other (Azevedo et al, 2017).
Against this background, Bossa et al (2017) monitored three neurogenic patients over 12 months by examining bacterial biofilms on their urinary catheters. The urinary tract microbiome differed significantly between individuals. Probiotic therapy and UTI (in one person) significantly changed the microbial community in the catheter biofilms. The change in the microbiome preceded the clinical diagnosis of UTI (Bossa et al, 2017). Nevertheless, the urinary microbiome was ‘highly resilient’ and ‘relatively stable’. The changes in the microbiota following probiotics or UTI were short-lived and soon returned to a pattern similar to the baseline composition (Bossa et al, 2017).
This study raises the prospect of monitoring individuals at risk of UTIs by establishing their baseline urinary microbiome (Bossa et al, 2017). A change in the microbiome may indicate that they are likely to develop an UTI. Identifying those at risk may reduce antibiotic use by, for example, changing catheters more often (Sidaway, 2017).
Nevertheless, a recent study of 15 premenopausal women without known urogenital disease or current symptoms reported that the urinary microbiota varied considerably over 6–18 months. Indeed, the urinary microbiota varied more than the faecal samples in the same person. Moreover, differences between volunteers accounted for almost half the variation in urinary microbiota (Biehl et al, 2022). Biehl et al (2022) commented that: ‘The higher intraindividual variability of urinary microbiota as compared to fecal microbiota will be a challenge for future studies investigating associations with urogenital diseases and aiming at identifying pathogenic microbiota signatures’.
The urinary microbiome does not tell the whole story. For instance, the interaction between tissues in the patient's bladder and the pathogens probably indicates the presence or absence of a UTI more accurately than the urinary microbiome alone (Forster et al, 2020). Nevertheless, further research into the biofilm and the urinary microbiome may offer new approaches to prevent catheter-related UTIs.