Intranasal Xylitol and Grapefruit Seed Extract Spray to Prevent Recurrent Acute Otitis Media in Children: A Multicenter Controlled Study

Background: Acute otitis media (AOM) is among the most frequent pediatric infections and a principal driver of antibiotic prescribing globally. Rising antimicrobial resistance and the limitations of current preventive strategies have increased interest in non-antibiotic intranasal approaches targeting nasopharyngeal colonization and biofilm formation. Aims: To evaluate the potential association between intranasal xylitol and grapefruit seed extract (XYL+GSE) administration and recurrent AOM-related outcomes in a pediatric outpatient population. Methods: A prospective multicenter exploratory controlled clinical study was conducted across 10 outpatient investigational sites in the Prague and Mid-Bohemia region of the Czech Republic. Pediatric outpatients aged 1-15 years with a history of recurrent AOM were prospectively assigned (non-randomized, fixed allocation schedule) to receive either intranasal XYL+GSE or a distilled-water comparator for 3 months. Outcome assessment was performed by study physicians; formal blinding of assessors was not implemented. Results: A total of 154 participants completed the 3-month treatment period (XYL+GSE: n = 80; control: n = 74). AOM recurrence occurred in 38.8% of participants in the XYL+GSE group compared with 90.5% in the control group (p < 0.001; absolute risk difference 51.8 percentage points, 95% CI 39.2-64.4; NNT = 2; exploratory estimate). Antibiotic use for AOM-related infections was significantly lower in the XYL+GSE group (11.3% vs. 35.1%; p < 0.001), as was overall antibiotic use for any infectious indication (32.5% vs. 52.7%; p = 0.011). Upper respiratory tract infection episodes were lower in the XYL+GSE group, but the difference did not reach statistical significance (p = 0.081). Exploratory microbiological analyses demonstrated an 87.5% reduction in total bacterial isolates in the XYL+GSE group versus 22.0% in controls. Conclusions: Intranasal XYL+GSE administration was associated with a lower rate of recurrent AOM and reduced antibiotic use in a pediatric outpatient population. These findings support the potential role of microbiome-targeted, non-antibiotic preventive strategies for recurrent upper respiratory infections. Given the non-randomized, exploratory design and absence of formal assessor blinding, results should be interpreted as hypothesis-generating and warrant confirmation in adequately powered, blinded randomized controlled trials. Keywords: Acute otitis media; xylitol; grapefruit seed extract; antimicrobial resistance; intranasal therapy; biofilm; pediatrics; nasopharyngeal colonization