{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:33:02Z","timestamp":1787581982192,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MCM Klosterfrau Vertriebsgesellschaft mbH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Antibiotics are the recommended first-line therapy for acute uncomplicated lower urinary tract infections (cystitis), but antibiotic resistance and tolerability concerns require antibiotic-sparing strategies. This study evaluated D-mannose as a stand-alone alternative. Methods: This multicenter, randomized, controlled, double-blind study compared D-mannose to fosfomycin in women aged 18\u201370 with cystitis. Clinical cure (CC) was assessed using the Acute Cystitis Symptom Score (ACSS) up to day 8, with non-inferiority tested at the 15% margin. Post hoc analytical approaches accounted for potential bias due to low sample sizes and missing values. Results: The study randomized 118 patients. At baseline, severe symptoms (ACSS \u2265 12) were more frequent in the D-mannose group compared to fosfomycin (32.8% vs. 22.8%). Efficacy analyses were performed on the per-protocol set (D-mannose: N = 57; fosfomycin: N = 54). Median time to CC was 5.0 days (D-mannose) and 3.0 days (fosfomycin) overall, and 4.0 days vs. 3.0 days in the subgroup of moderate disease severity. The point estimate for the CC rate difference on day 8 (\u221210.1%) favored fosfomycin but was within the non-inferiority margin. Due to wide confidence intervals, non-inferiority was not statistically confirmed. The post hoc analysis yielded smaller confidence intervals with estimated CC rates of 84.2% (D-mannose) vs. 83.5% (fosfomycin) on day 8 and statistically demonstrated the comparability of both treatments. Recurrence rates were similar (13.2% vs. 13.3%), and there was no statistically significant difference for additional antibiotic use (19.3% vs. 11.1%). Investigators and patients favored D-mannose over fosfomycin for tolerability, and gastrointestinal adverse events were less frequent (9.8% vs. 24.6%). Conclusions: Post hoc analysis indicated that D-mannose treatment is comparable to fosfomycin in uncomplicated cystitis in line with the prespecified non-inferiority criteria. These findings warrant confirmation in an adequately powered trial but suggest that D-mannose is a promising alternative to antibiotics given its favorable risk\u2013benefit ratio.<\/jats:p>","DOI":"10.3390\/antibiotics15090820","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:20:43Z","timestamp":1787577643000},"page":"820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First Randomized Controlled Trial Comparing D-Mannose to Fosfomycin in Acute Uncomplicated Lower Urinary Tract Infections"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2909-0797","authenticated-orcid":false,"given":"Florian","family":"Wagenlehner","sequence":"first","affiliation":[{"name":"Clinic for Urology, Pediatric Urology and Andrology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidrun","family":"Taeschner","sequence":"additional","affiliation":[{"name":"Internistische Facharztpraxis, 04249 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Lorenz","sequence":"additional","affiliation":[{"name":"BBS Neuberg, B\u00fcro f\u00fcr Biometrie und Statistik, Im Unterfeld 17, 63543 Neuberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Berwanger","sequence":"additional","affiliation":[{"name":"MCM Klosterfrau Vertriebsgesellschaft mbH, Gereonsmuehlengasse 1-11, 50670 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nacera","family":"Infed","sequence":"additional","affiliation":[{"name":"MCM Klosterfrau Vertriebsgesellschaft mbH, Gereonsmuehlengasse 1-11, 50670 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oda","family":"Ewald","sequence":"additional","affiliation":[{"name":"MCM Klosterfrau Vertriebsgesellschaft mbH, Gereonsmuehlengasse 1-11, 50670 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gerke","sequence":"additional","affiliation":[{"name":"MCM Klosterfrau Vertriebsgesellschaft mbH, Gereonsmuehlengasse 1-11, 50670 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.idc.2013.09.003","article-title":"Urinary tract infection syndromes: Occurrence, recurrence, bacteriology, risk factors, and disease burden","volume":"28","author":"Foxman","year":"2014","journal-title":"Infect. 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