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<b><i>Introduction:</i></b> Recurrent urinary tract infections (rUTIs) affect 5–10% of women, resulting in an enormous healthcare and society burden. Uromune® is a polybacterial sublingual vaccine with an excellent clinical benefit in rUTI prophylaxis. This study assesses the impact of sublingual vaccination on healthcare resource use and expenditures associated with this pathology. <b><i>Methods:</i></b> A quasi-experimental, pretest-posttest, single center study including women with rUTI and vaccinated with Uromune® in real-life clinical practice was performed. Variables were the need of healthcare resources, collected prospectively during two follow-up years, and the rUTI-associated expenditure, calculated using the micro-costing methodology; these were compared before and after vaccination. <b><i>Results:</i></b> A total of 166 women {mean (standard deviation [SD]) urinary tract infection episodes/year 6.19 (2.15)} were included. After vaccination, annual consultations with a primary care physician (PCP) (43.9%), emergency room visits (71.8%), urinary analysis (90.0%), and ultrasound exams (35.6%) decreased compared to pre-vaccination (all <i>p</i> &#x3c; 0.001). Per patient consumption in antibiotics, PCP consultations, emergency room visits, and complementary exams significantly decreased (all <i>p</i> &#x3c; 0.02), resulting in a reduction in healthcare expenditure per patient/year from mean (SD) 1,001.1 (655.0) to 497.1 (444.4) EUR. <b><i>Conclusion:</i></b> Sublingual bacterial vaccination with Uromune® decreased healthcare resource use and associated expenditure in women with rUTI, representing an optimal strategy to reduce rUTI-associated healthcare and economic burden.

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