Preventing urinary tract infections (UTIs) in those who are prone is of paramount importance, particularly in children. While prevention should focus on identifying modifiable risk factors, such as voiding behaviors and constipation, or anatomical features requiring surgical intervention, sometimes such causes are unclear. As a result, chronic antibiotic therapy has been used to prevent UTIs. In the adult literature, antibiotic suppressive therapy has been utilized successfully in preventing UTIs. The pediatric literature is somewhat conflicted, drawing into question its regular practice. While certain landmark pediatric studies have found antibiotic prophylaxis decreases recurrent UTIs in children both with and without vesicoureteral reflux (VUR),^1,2 a 2019 Cochrane Database systematic review did not support antibiotic prophylaxis in pediatric patients with primary VUR.³

Further complicating its regular use is the concern for rising bacterial antibiotic resistance rates and the risk of side effects. Such concerns question long-term antibiotic use and highlight the need for alternative means of prevention, particularly in the pediatric population. D-Mannose and cranberry products have been investigated as alternatives in UTI prevention due to their ability to limit bacterial attachment to the urinary tract.

D-Mannose is a monosaccharaide isomer of glucose rapidly absorbed in powder formulation in the gut and excreted in the urine where it competitively inhibits bacterial attachment to the urinary tract. Clinical studies using D-mannose for UTI prophylaxis are limited, with none performed in children. One of the only randomized controlled trials of D-mannose monotherapy use to prevent recurrent UTIs found D-mannose as effective as daily prophylactic nitrofurantoin use in preventing UTIs, and more effective than no intervention.⁴ Those on D-mannose did report fewer side effects than those on antibiotics (7.8% vs 27.2%, p <0.0001). Other studies of D-mannose’s efficacy in UTI prevention have included it as part of a cocktail of dietary supplements with heterogeneity of the supplemental products used and small patient numbers. A systematic review of D-mannose use in adult UTI prevention found a protective effect of D-mannose compared to placebo (RR 0.23, 95% CI 0.14–0.37), with similar efficacy to antibiotic use (RR 0.39, 95% CI 0.12–1.25).⁵ Ongoing investigations are promised, with a randomized controlled double-blinded study proposed for 2021 in the United Kingdom (the MERIT study) comparing D-mannose to placebo alone.

Cranberry has similarly been investigated clinically for its ability to prevent bacterial attachment in the urinary tract. There are pediatric specific studies reviewing its use in children both with and without VUR, with mixed results. A large trial of predominantly female children with a history of UTI randomized to either cranberry juice or placebo found a significant reduction in the density of UTIs (p=0.035) and a reduction in antibiotic use in those taking cranberry juice.⁶ There was no difference, however, between groups in the overall number of children experiencing a UTI (p=0.21). It should be noted that this study did include patients with nondilating VUR, although the overall number with VUR was small. In the only study comparing cranberry juice to daily antibiotic prophylaxis (cefaclor), investigators found a comparable effect between the two on UTI occurrence in children with VUR.⁷ This study, however, only included 12 and 19 patients in each group, respectively.

Systematic reviews on cranberry juice use in UTI prevention have primarily combined adult and pediatric studies, with subsequent subgroup analyses done in the pediatric population. The most recent Cochrane Database systematic review does not advocate the use of cranberry juice to prevent UTIs, finding no benefit of cranberry products compared to either placebo or antibiotics in reducing UTIs in children.⁸ The review does note high study dropout rates due to the poor taste of the cranberry product and issues with cranberry dosing quantification and standardization. Conversely, a smaller systematic review found a positive effect of cranberry products in protecting against UTIs in children (RR 0.33, 95% CI 0.16–0.69).⁹ Interestingly, they found that cranberry juice was more effective than cranberry capsules or tablets and recommended at least twice-daily dosing for 6 months. There has been only 1 systematic review specifically of pediatric studies. It found that cranberry products were as effective as antibiotic prophylaxis (RR 0.92, 95% CI 0.56–1.5; although based upon the single study comparing the 2 treatments mentioned above) and better than no therapy or placebo (RR 0.48, 95% 0.28–0.8) in preventing UTIs in children with normal urinary tracts. This review did note an unclear risk of bias in all studies reviewed, limiting the authors from universally recommending cranberry prophylaxis.¹⁰

Concerns regarding cranberry product use relate to a lack of standardized dosing and limitations around its tolerability. Suggested adult dosing is between 36–72 mg of proanthocyanidin containing cranberry product per day, with up to 300 ml of 5 ml/kg cranberry juice per day suggested in children. Pure cranberry juice is too acidic (pH <2) to ingest alone; cranberry cocktail is typically 33% cranberry juice. While overall considered safe, there has been concern that cranberry juice may increase the risk of developing calcium oxalate and uric acid stones, but without conclusive data.

It is clear prevention of UTIs is important in the pediatric population, with alternatives to antibiotic use desirable. While D-mannose has some promise with continuing evaluation of its use actively in progress, use in the pediatric population is extrapolated from adult literature with studies needed in children. Cranberry products may be useful but require further investigation with larger sample sizes. In addition, dosages and formulation have to be clarified with attention to improving tolerability.