Hello urologists, gynaecologists, primary care doctors and all of you who have to deal with urinary tract infections. Urinary tract infection management and prevention is one of the activities on a routine basis for all caregivers. This Newsletter intends to review the last recommendations for managing and preventing urinary infections. Our focus is reducing the number of infections, avoiding antibiotic use when not indicated to prevent resistance and reviewing the evidence about non-antibiotic measures to prevent infections. Scientific support of the evidence and practice guidelines recommendations will be the key to all the information in the Newsletter.

The first article addresses the impact urine pH in the transcripticon of genes that regulated the expresión of adhesión proteins of Escherichia coli.

The second article reviews the effect of drugs used in the management of diabetes mellitus in the incidence of urinary tract ingfections and recommendations about siscontinuation. 

The third article discusses strategies for the prevention of UTIs in elderly patients with the focus in the evidence about Utipro^® Plus AF.

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This study evaluates the influence of pH and osmolarity on the expression of adhesion proteins in Escherichia coli. These proteins, particularly type 1 pili and the fim gene cluster, are essential for the pathogenesis of urinary tract infections, as bacterial adhesion to urothelial cells is required for colonization. Type 1 fimbriae are expressed in approximately 70% of uropathogenic E. coli strains. Cranberry extracts and D-mannose are commonly used to inhibit pili-mediated adhesion to urothelial cells as a preventive strategy for urinary tract infections.

The study consists of a comparative analysis assessing the effect of different pH values and osmolarity conditions on the transcription of genes responsible for bacterial adhesion. It examines various osmolarity ranges and compares adhesion capacity and gene expression at pH 5.5 versus pH 7. The findings show that the expression of fim promoters (fimA, fimB, and fimE) is reduced in acidic environments.

• fimA: encodes the structural protein FimA of type 1 fimbriae
• fimB: promotes fimbrial activation (phase ON)
• fimE: promotes fimbrial deactivation (phase OFF)

Increased osmolarity and neutral pH are associated with an approximately 50% increase in transcription of fimA and fimB. Moreover, fimE expression doubles under these conditions, contributing to the inhibition of adhesion. The study demonstrates the greatest effect on gene transcription when using urine specimens with a pH around 5.5 and osmolarity between 250 and 300 mM (0.8–0.9 mol/kg). Thus, urinary acidification, in addition to its bacteriostatic and bactericidal effects that help prevent urinary tract infections, may also exert a specific inhibitory effect on bacterial adhesion.

It is important to consider that urinary pH can vary between 5 and 8, and treatments capable of modifying urinary pH (such as Metiofitina^®) may be useful in patients with recurrent urinary tract infections. Furthermore, the efficacy of commonly used antibiotics is influenced by urinary pH; antibiotics frequently prescribed for urinary infections tend to be more effective in acidic urine.

In summary, urinary acidification reduces the expression of type 1 fimbriae on the bacterial surface and promotes their deactivation, thereby limiting the ability of E. coli to adhere to the urothelium and colonize the bladder.

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This study evaluates the effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors in patients with diabetes mellitus. Diabetes mellitus is considered a risk factor for urinary tract infections (UTIs), as it may impair immune function and contribute to bladder dysfunction. In addition, poorly controlled diabetes increases the risk of systemic symptoms and more severe or complicated infections. The use of SGLT2 inhibitors is common in diabetic patients, and these agents have been associated with an increased incidence of UTIs. The aim of the study is to assess whether discontinuation of SGLT2 inhibitors is warranted, given that a higher number of UTIs may lead to increased antibiotic use and its associated consequences.

A 7-year cohort study was conducted, including 61,000 patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. Six percent had experienced at least one UTI during the preceding year. The primary objective was to evaluate the incidence of cardiovascular events and to determine whether these were associated with the occurrence of UTIs. The authors report that patients who developed UTIs had a higher risk of cardiovascular events and worsened renal function. As SGLT2 inhibitors increase the incidence of UTIs, the study found that 32.31% of patients discontinued these medications after experiencing a UTI. However, discontinuation of SGLT2 inhibitors was associated with a higher risk of cardiovascular (HR 1.35, 95% CI 1.20–1.53) and renal outcomes (HR 1.35, 95% CI 1.21–1.51). In contrast, continuing SGLT2 inhibitor therapy in these patients was not associated with an increased risk of recurrent UTIs.

Therefore, the authors conclude that new-onset UTI is associated with an increased risk of cardiovascular and renal events in patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. Discontinuing SGLT2 inhibitors after a UTI is linked to a higher risk of adverse cardiovascular and renal outcomes and does not reduce the likelihood of recurrent UTI. Thus, the development of new-onset UTI may serve as a clinical marker of subsequent adverse events and supports the continuation of SGLT2 inhibitor therapy after a UTI to help mitigate complications associated with type 2 diabetes mellitus.

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Urinary tract infections (UTIs) are common in the elderly, particularly among institutionalized individuals and those with urinary catheters. The incidence of UTIs in women over 55 years of age is estimated at 7 cases per 100 person-years and the prevalence can reach up to 50% in institutionalized patients. Older adults also have a higher risk of sepsis and more unfavorable clinical courses when UTIs occur. In addition to sporadic infections, this population has an increased predisposition to recurrent UTIs.

This study reviews alternatives to low-dose antibiotic prophylaxis in elderly patients, following the recommendations of the European Association of Urology guidelines. Among the non-antibiotic strategies, the use of topical estrogens should be considered in postmenopausal women. The study also provides a detailed analysis of treatment options based on xyloglucan.

Xyloglucan is a hemicellulose extracted from tamarind seeds that helps restore the integrity and function of mucosal epithelial cells. By forming a bio-protective film, xyloglucan prevents direct contact between mucosal surfaces and pathogens, toxins, allergens, and pro-inflammatory molecules. The formulation Utipro^® Plus AF, which contains xyloglucan 100 mg and gelose 50 mg, has demonstrated efficacy in both in vitro and in vivo studies. In vitro models, the product was shown to create a physical protective barrier on human intestinal epithelial cells, preventing intracellular invasion by E. coli. In experimental rat models of acute infectious gastroenteritis and UTI, preventive treatment with oral xyloglucan–gelose prior to infection induction significantly reduced intestinal morphological alterations, tight-junction permeability, and neutrophil infiltration. Several human studies have also reported that xyloglucan combined with gelose significantly decreases the frequency of urinary incontinence and urgency in patients with UTIs.

For the prevention of recurrent UTIs, the recommended dose is one capsule daily for 15 days each month over a 6 month period, with the aim of reducing the incidence of symptomatic infections. The authors conclude that Utipro^® Plus AF may be useful in decreasing the frequency of symptomatic UTIs. The observation that many patients transition to asymptomatic bacteriuria, potentially protective against symptomatic recurrences, is noteworthy and suggests that the product does not adversely affect the normal microbiota.