{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:06:30Z","timestamp":1792181190766,"version":"4.4.0"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Urinary tract infections (UTI) are highly frequent in women, with a significant impact on healthcare resources. Although antibiotics still represent the standard treatment to manage recurrent UTI (rUTI), D-mannose, an inert monosaccharide that is metabolized and excreted in urine and acts by inhibiting bacterial adhesion to the urothelium, represents a promising nonantibiotic prevention strategy. The aim of this narrative review is to critically analyze clinical studies reporting data concerning the efficacy and safety of D-mannose in the management of rUTIs. Methods: A non-systematic literature search, using the Pubmed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases, was performed for relevant articles published between January 2010 and January 2021. The following Medical Subjects Heading were used: \u201cfemale\/woman\u201d, \u201curinary tract infection\u201d, and \u201cD-mannose\u201d. Only clinical studies, systematic reviews, and meta-analyses reporting efficacy or safety data on D-mannose versus placebo or other competitors were selected for the present review. Evidence was limited to human data. The selected studies were organized in two categories according to the presence or not of a competitor to D-mannose. Results: After exclusion of non-pertinent studies\/articles, 13 studies were analyzed. In detail, six were randomized controlled trials (RCTs), one a randomized cross-over trial, five prospective cohort studies, and one a retrospective analysis. Seven studies compared D-mannose to placebo or others drugs\/dietary supplements. Six studies evaluated the efficacy of D-mannose comparing follow-up data with the baseline. D-mannose is well tolerated, with few reported adverse events (diarrhea was reported in about 8% of patients receiving 2 g of D-mannose for at least 6 months). Most of the studies also showed D-mannose can play a role in the prevention or rUTI or urodynamics-associated UTI and can overlap antibiotic treatments in some cases. The possibility to combine D-mannose with polyphenols or Lactobacillus seems another important option for UTI prophylaxis. However, the quality of the collected studies was very low, generating, consequently, a weak grade of recommendations as suggested by international guidelines. Data on D-mannose dose, frequency, and duration of treatment are still lacking. Conclusion: D-mannose alone or in combination with several dietary supplements or Lactobacillus has a potential role in the non antimicrobial prophylaxis or recurrent UTI in women. Despite its frequent prescription in real-life practice, we believe that further well-designed studies are urgently needed to definitively support the role of D-mannose in the management of recurrent UTIs in women.<\/jats:p>","DOI":"10.3390\/antibiotics10040373","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:23:17Z","timestamp":1617261797000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Role of D-Mannose in the Prevention of Recurrent Uncomplicated Cystitis: State of the Art and Future Perspectives"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2190-512X","authenticated-orcid":false,"given":"Cosimo","family":"De Nunzio","sequence":"first","affiliation":[{"name":"Department of Urology, Sant\u2019Andrea Hospital, Sapienza University of Rome, 00141 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bartoletti","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies, Urology Unit, University of Pisa, 56010 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tubaro","sequence":"additional","affiliation":[{"name":"Department of Urology, Sant\u2019Andrea Hospital, Sapienza University of Rome, 00141 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-4869","authenticated-orcid":false,"given":"Alchiede","family":"Simonato","sequence":"additional","affiliation":[{"name":"Department of Surgical, Oncological and Oral Sciences, Urology Section, University of Palermo, 90121 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Ficarra","sequence":"additional","affiliation":[{"name":"Department of Human and Pediatric Pathology \u201cGaetano Barresi\u201d, Urology Section, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2020.05.048","article-title":"D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: A systematic review and meta-analysis","volume":"223","author":"Lenger","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"570","DOI":"10.23736\/S0393-2249.18.03233-2","article-title":"Intraprostatic injections for lower urinary tract symptoms\/benign prostatic enlargement treatment","volume":"70","author":"Lombardo","year":"2018","journal-title":"Minerva Urol. Nefrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.eururo.2020.06.032","article-title":"The EAU and AUA\/CUA\/SUFU Guidelines on Recurrent Urinary Tract Infections: What is the Difference?","volume":"78","author":"Naber","year":"2020","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kyriakides, R., Jones, P., and Somani, B.K. (2020). Role of D-Mannose in the Prevention of Recurrent Urinary Tract Infections: Evidence from a Systematic Review of the Literature. Eur. Urol. Focus, 2\u20135.","DOI":"10.1016\/j.euf.2020.09.004"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s00192-014-2569-5","article-title":"Recurrent urinary tract infections in women","volume":"26","author":"Aydin","year":"2015","journal-title":"Int. Urogynecol. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1007\/s10753-013-9650-y","article-title":"Quorum sensing signal molecules produced by Pseudomonas aeruginosa cause inflammation and escape host factors in murine model of urinary tract infection","volume":"36","author":"Gupta","year":"2013","journal-title":"Inflammation"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pirozzi, L., Sountoulides, P., Castellan, P., Presicce, F., Lombardo, R., Romero, M., De Nunzio, C., Tubaro, A., Schips, L., and Cindolo, L. (2015). Current Pharmacological Treatment for Male LUTS due to BPH: Dutasteride or Finasteride?. Curr. Drug Targets, 16.","DOI":"10.2174\/1389450116666150518101617"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.2174\/1389450116666150806124345","article-title":"The current indications and the benefits of combining a \u03b23-agonist with an anticholinergic for the treatment of OAB","volume":"16","author":"Presicce","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Scribano, D., Sarshar, M., Prezioso, C., Lucarelli, M., Angeloni, A., Zagaglia, C., Palamara, A.T., and Ambrosi, C. (2020). D-Mannose treatment neither affects uropathogenic Escherichia coli properties nor induces stable fimh modifications. Molecules, 25.","DOI":"10.3390\/molecules25020316"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.1128\/iai.65.10.4199-4206.1997","article-title":"Specificity of the high-mannose recognition site between Enterobacter cloacae pili adhesin and HT-29 cell membranes","volume":"65","author":"Pan","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1073\/pnas.92.6.2081","article-title":"FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae","volume":"92","author":"Jones","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.urology.2010.01.068","article-title":"Novel concentrated cranberry liquid blend, UTI-STAT with proantinox, might help prevent recurrent urinary tract infections in women","volume":"76","author":"Efros","year":"2010","journal-title":"Urology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S96","DOI":"10.1097\/MCG.0000000000000224","article-title":"Effectiveness of an association of a cranberry dry extract, D-mannose, and the two microorganisms Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09 in women affected by cystitis: A pilot study","volume":"48","author":"Vicariotto","year":"2014","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_14","first-page":"2920","article-title":"D-mannose: A promising support for acute urinary tract infections in women. A pilot study","volume":"20","author":"Domenici","year":"2016","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1002\/nau.23173","article-title":"Open label feasibility study evaluating D-mannose combined with home-based monitoring of suspected urinary tract infections in patients with multiple sclerosis","volume":"36","author":"Pakzad","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_16","first-page":"931","article-title":"Efficacy of N-acetylcysteine, D-mannose and morinda citrifolia to treat recurrent cystitis in breast cancer survivals","volume":"31","author":"Marchiori","year":"2017","journal-title":"In Vivo"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/1120009X.2017.1393587","article-title":"Effects of a new combination of plant extracts plus d-mannose for the management of uncomplicated recurrent urinary tract infections","volume":"30","author":"Genovese","year":"2018","journal-title":"J. Chemother."},{"key":"ref_18","first-page":"101","article-title":"Recurrent bacterial symptomatic cystitis: A pilot study on a new natural option for treatment","volume":"9","author":"Nelli","year":"2018","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s00345-013-1091-6","article-title":"D-mannose powder for prophylaxis of recurrent urinary tract infections in women: A randomized clinical trial","volume":"32","author":"Altarac","year":"2014","journal-title":"World J. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Porru, D., Parmigiani, A., Tinelli, C., Barletta, D., Choussos, D., Di Franco, C., Bobbi, V., Bassi, S., Miller, O., and Gardella, B. (2014). Oral D-mannose in recurrent urinary tract infections in women: A pilot study. J. Clin. Urol., 7.","DOI":"10.1177\/2051415813518332"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4081\/aiua.2017.1.45","article-title":"Prospective study to compare antibiosis versus the association of N-acetylcysteine, D-mannose and Morinda citrifolia fruit extract in preventing urinary tract infections in patients submitted to urodynamic investigation","volume":"89","author":"Palleschi","year":"2017","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_22","first-page":"336","article-title":"Eval uation of the effects of a natural dietary supplement with cranberry, noxamicina and d-mannose in recurrent urinary infections in perimenopausal women","volume":"69","author":"Cappelli","year":"2017","journal-title":"Minerva Ginecol."},{"key":"ref_23","first-page":"169","article-title":"Eficacia y tolerancia terap\u00e9utica de la d-manosa (2 g) de liberaci\u00f3n prolongada 24 horas (asociada a proantocianidinas), frente a proantocianidinas aisladas en el manejo de una serie de mujeres con infecciones urinarias recurrentes","volume":"71","year":"2018","journal-title":"Arch. Espa\u00f1oles Urol."},{"key":"ref_24","first-page":"491","article-title":"Amplio estudio (283 mujeres) sobre la eficacia de manosar\u00ae: 2 G de d-manosa + 140 Mg de proantocianidinas (PAC), de liberaci\u00f3n prolongada frente a 240 mg de pac de liberaci\u00f3n prolongada en la prevenci\u00f3n a 6 meses por V\u00cda oral de las infecciones urinarias recurrentes","volume":"73","year":"2020","journal-title":"Arch. Espa\u00f1oles Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1111\/j.1365-2958.2004.04415.x","article-title":"Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin","volume":"55","author":"Bouckaert","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1021\/acs.jafc.5b05610","article-title":"Structural Characterization and Immunomodulatory Activity of a Novel Polysaccharide from Lepidium meyenii","volume":"64","author":"Zhang","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mousavifar, L., and Roy, R. (2019). Alternative therapeutic strategies to fight bacterial infections. Front. Drug Chem. Clin. Res., 2.","DOI":"10.15761\/FDCCR.1000115"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mousavifar, L., and Roy, R. (2021). Recent development in the design of small \u2018drug-like\u2019 and nanoscale glycomimetics against Escherichia coli infections. Drug Discov. Today.","DOI":"10.1016\/j.drudis.2021.02.025"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sarshar, M., Behzadi, P., Ambrosi, C., Zagaglia, C., Palamara, A.T., and Scribano, D. (2020). FimH and anti-adhesive therapeutics: A disarming strategy against uropathogens. Antibiotics, 9.","DOI":"10.3390\/antibiotics9070397"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/4\/373\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:10:51Z","timestamp":1760364651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/4\/373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,1]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["antibiotics10040373"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10040373","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,1]]}}}