Nonantibiotic prevention and management of recurrent urinary tract infection


Urinary tract infections (UTIs) are highly prevalent, lead to considerable patient morbidity, incur large financial costs to health-care systems and are one of the most common reasons for antibiotic use worldwide. The growing problem of antimicrobial resistance means that the search for nonantibiotic alternatives for the treatment and prevention of UTI is of critical importance. Potential nonantibiotic measures and treatments for UTIs include behavioural changes, dietary supplementation (such as Chinese herbal medicines and cranberry products), NSAIDs, probiotics, d-mannose, methenamine hippurate, estrogens, intravesical glycosaminoglycans, immunostimulants, vaccines and inoculation with less-pathogenic bacteria. Some of the results of trials of these approaches are promising; however, high-level evidence is required before firm recommendations for their use can be made. A combination of these agents might provide the optimal treatment to reduce recurrent UTI, and trials in specific population groups are required.

Key points

  • Rising rates of antimicrobial resistance, fuelled by the overuse of antibiotics in humans, are a serious threat to global public health.

  • Alternatives to antibiotics for the prevention of recurrent urinary tract infection (UTI) are attractive options to reduce the risks of antimicrobial resistance.

  • The most commonly studied nonantibiotic management options for recurrent UTI include cranberries, probiotics, d-mannose, methenamine hippurate, estrogens, intravesical glycosaminoglycans and immunostimulants.

  • Studies of novel vaccines targeting the adherence mechanisms of uropathogenic bacteria seem promising, but human trials are required to determine the efficacy of this approach.

  • Evidence for the nonantibiotic measures is hampered by considerable heterogeneity, and further placebo-controlled randomized trials of these agents are needed.

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Fig. 1: Pathogenesis of urinary tract infection.
Fig. 2: Mechanisms of antimicrobial resistance by mobile genetic elements.
Fig. 3: Mechanisms of action of cranberry components in prevention of urinary tract infection.
Fig. 4: A-type and B-type linkages of proanthocyanidins.
Fig. 5: Mechanisms of action of lactobacilli in urinary tract infection prevention.
Fig. 6: Type 1 pili of Escherichia coli and the uroplakin 1a receptor.
Fig. 7: d-Mannose prevents binding of bacteria to urothelial cells.
Fig. 8: Chemical structure of heptyl-α-d-mannose.
Fig. 9: Structure of the glycosaminoglygan layer of the bladder wall.
Fig. 10: Nonantibiotic interventions for urinary tract infection.


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Nature Reviews Urology thanks T. J. Hannan, F. Wagenlehner and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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N.S., A.G., R.Z., A.S. and S.M. researched data for the article. S.M. made substantial contributions to discussions of content. All authors wrote the manuscript, and S.M. reviewed and edited the manuscript before submission.

Correspondence to Sachin Malde.

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N.S., A.G. and R.Z. declare no competing interests. A.S. has received an unrestricted educational grant, is an adviser to and has received speaker fees from Allergan Ltd. and has received monies from Medtronic for promotional purposes. S.M. has received monies from Medtronic for promotional purposes.

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Sihra, N., Goodman, A., Zakri, R. et al. Nonantibiotic prevention and management of recurrent urinary tract infection. Nat Rev Urol 15, 750–776 (2018).

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