Bladder extracellular matrix replenishment to prevent recurrent urinary tract infections in children

With the evolving antibiotic crisis, alternate strategies to treat or prevent urinary tract infections (UTI) in children are necessary. One area of interest includes strategies that replenish or repair damaged bladder extracellular matrix. Reports of treatments include oral dimethyl sulfoxide, pentosan polysulfate and intravesical glycoaminoglycans (GAG). These treatments have established practice in adults for bladder pain and ketamine bladder and prevention of UTI. We aim to summarise the basic sciences, the putative mechanisms of actions, the evidence for GAG and alternate bladder repair treatments in adults and children for the prevention of urinary tract infections. We reviewed the literature, utilising expert librarian assistance, and using Pub Med, Google and AI search engines to find papers pertaining to bladder extracellular matrix, urothelium, glycoaminoglycans and other synonyms for the class of treatments of bladder repair and inspected in the context of urinary tract infections. We additionally undertook expert conversations to enrich this review discussion. The basic sciences show encouraging findings of in-vitro and animal models for bacterial adherence improvements and anti-bacterial effects with GAG therapies. Anti-inflammatory effects are also seen. Arguments of the primacy of bladder extracellular matrix as anti-bacterial defense do not stand to scrutiny. The clinical evidence for GAG therapy is most convincing in the field of post-menopausal women with dysbiosis and adult bladder pain syndrome (BPS). In most papers structural and functional bladder patients are excluded. The clinical evidence for prevention of UTI in adults in high quality large scale randomisation is missing, but there is good promise in smaller cohort studies. Many of the reported papers utilise the EAU definition of UTI of symptoms and / OR culture which means efficacy may be relief of lower urinary tract symptoms, rather than prevention of disease. There are protocols and active recruitment to multicentre randomised trials in adult UTI. The evidence in children is limited but small scale single centre cohorts show positive effects of intravesical GAG. Bladder treatments have a good safety profile but questions must be raised to cost and tolerability in children as the delivery method requires catheterisation. Good quality evidence for bladder repair therapies remains limited for prevention of UTI in children. The putative mechanism of bacterial anti-adherence and bladder protection is intellectually intriguing. The clinical evidence of benefit is predominantly in preventing UTI is the setting of adult dysbiosis. We suggest caution in applying evidence in populations excluding functional and anatomical anomalies to pediatric UTI but recognise a limited role in selected children, especially those already catheterizing, resistant to other methods of UTI prevention.