{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T02:01:15Z","timestamp":1782698475652,"version":"3.54.5"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,12,7]],"date-time":"2019-12-07T00:00:00Z","timestamp":1575676800000},"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: Antibiotics are commonly used as first-line treatment for acute lower uncomplicated urinary tract infections (uUTIs). However, antimicrobial resistance is a growing global problem and efficacious nonantibiotic treatment options are urgently needed. Methods: A secondary analysis was conducted with data from a randomized, controlled, double-blind trial comparing a fixed combination of extracts of restharrow root, Java tea, and goldenrod herb (Aqualibra\u00ae) to placebo in 200 women with acute lower uUTI. Symptom scores reported in the original trial were reanalyzed and adjusted to the definitions of the Acute Cystitis Symptom Score (ACSS). Results: Based on a subgroup of patients with evaluable microbiologic data (n = 122), the decrease of the mean sum-score of three typical ACSS-adjusted symptoms showed significant superiority of the herbal preparation over placebo already after one day of treatment (p = 0.0086); on Day 7, the average difference was \u22121.9 score points (p &lt; 0.0001). The superior efficacy of the herbal preparation on Day 1 was mainly driven by a difference in response rates of the symptom \u2018dysuria\u2019 (group difference: \u221229.4%, p = 0.0042). Furthermore, significantly fewer patients in the verum group required antibiotic therapy (15.3% vs. 49.2%, p = 0.0001). These results were confirmed in the intention-to-treat (ITT) population (n = 200). Conclusions: A fixed combination of extracts of restharrow root, Java tea, and goldenrod herb was superior to placebo regarding symptom relief and prevention of antibiotic use in women with lower uUTI. Trial registration: ClinicalTrials.gov: NCT04032574.<\/jats:p>","DOI":"10.3390\/antibiotics8040256","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T05:54:51Z","timestamp":1575870891000},"page":"256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effect of a Herbal Therapy on Clinical Symptoms of Acute Lower Uncomplicated Urinary Tract Infections in Women: Secondary Analysis from a Randomized Controlled Trial"],"prefix":"10.3390","volume":"8","author":[{"given":"Winfried","family":"Vahlensieck","sequence":"first","affiliation":[{"name":"Department of Urology, Kurpark-Klinik, Kurstra\u00dfe 41-45, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst","family":"Lorenz","sequence":"additional","affiliation":[{"name":"BBS\u2014B\u00fcro f\u00fcr Biometrie und Statistik, Im Unterfeld 17, 63543 Neuberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Schumacher-Stimpfl","sequence":"additional","affiliation":[{"name":"Medice Arzneimittel P\u00fctter GmbH &amp; Co. KG, Kuhloweg 37, 58638 Iserlohn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Fischer","sequence":"additional","affiliation":[{"name":"Medice Arzneimittel P\u00fctter GmbH &amp; Co. KG, Kuhloweg 37, 58638 Iserlohn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Naber","sequence":"additional","affiliation":[{"name":"Department of Urology, Technical University of Munich, Urology, Ismaninger Str. 22, 81675 M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrurol.2010.190","article-title":"The epidemiology of urinary tract infection","volume":"7","author":"Foxman","year":"2010","journal-title":"Nat. Rev. Urol."},{"key":"ref_2","unstructured":"(2019, October 10). The European Association of Urology (EAU) Guidelines. Edn. Presented at the EAU Annual Congress Copenhagen. Available online: http:\/\/uroweb.org\/guideline\/urological-infections\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0140-6736(05)17907-0","article-title":"Outpatient antibiotic use in Europe and association with resistance: A cross-national database study","volume":"365","author":"Goossens","year":"2005","journal-title":"Lancet"},{"key":"ref_4","first-page":"791","article-title":"Resistance patterns of nosocomial urinary tract infections in urology departments: 8-year results of the global prevalence of infections in urology study","volume":"32","author":"Tandogdu","year":"2014","journal-title":"World J. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ijantimicag.2009.04.012","article-title":"The ARESC study: An international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections","volume":"34","author":"Schito","year":"2009","journal-title":"Int. J. Antimicrob. Agents."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/jac\/dkg028","article-title":"An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: The ECO.SENS Project","volume":"51","author":"Kahlmeter","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","unstructured":"Leitlinienprogramm, DGU (2019, December 04). AWMF: Interdisziplin\u00e4re S3 Leitlinie: Epidemiologie, Diagnostik, Therapie, Pr\u00e4vention und Management Unkomplizierter, Bakterieller, Ambulant Erworbener Harnwegsinfektionen bei Erwachsenen Patienten. Kurzversion 1.1.-2. 2017 AWMF Registernummer: 043\/044. Available online: https:\/\/www.awmf.org\/uploads\/tx_szleitlinien\/043-044k_S3_Harnwegsinfektionen_2017-05.pdf."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"j4784","DOI":"10.1136\/bmj.j4784","article-title":"Symptomatic treatment of uncomplicated lower urinary tract infections in the ambulatory setting: Randomised, double blind trial","volume":"359","author":"Kronenberg","year":"2017","journal-title":"BMJ"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"h6544","DOI":"10.1136\/bmj.h6544","article-title":"Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: Randomised controlled trial","volume":"351","author":"Gagyor","year":"2015","journal-title":"BMJ"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Vik, I., Bollestad, M., Grude, N., Baerheim, A., Damsgaard, E., Neumark, T., Bjerrum, L., Cordoba, G., Olsen, I.C., and Lindb\u00e6k, M. (2018). Ibuprofen versus pivmecillinam for uncomplicated urinary tract infection in women\u2014A double-blind, randomized non-inferiority trial. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002569"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Afshar, K., Fleischmann, N., Schmiemann, G., Bleidorn, J., Hummers-Pradier, E., Friede, T., Wegscheider, K., Moore, M., and G\u00e1gyor, I. (2018). Reducing antibiotic use for uncomplicated urinary tract infection in general practice by treatment with uva-ursi (REGATTA)\u2014A double-blind, randomized, controlled comparative effectiveness trial. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2266-x"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1159\/000493368","article-title":"Non-Antibiotic Herbal Therapy (BNO 1045) versus Antibiotic Therapy (Fosfomycin Trometamol) for the Treatment of Acute Lower Uncomplicated Urinary Tract Infections in Women: A Double-Blind, Parallel-Group, Randomized, Multicentre, Non-Inferiority Phase III Trial","volume":"101","author":"Wagenlehner","year":"2018","journal-title":"Urol. Int."},{"key":"ref_13","unstructured":"European Medicines Agency (2019, December 04). Assessment Report on Orthosiphon stamineus Benth., folium. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/herbal-report\/final-assessment-report-orthosiphon-stamineus-benth-folium_en.pdf."},{"key":"ref_14","unstructured":"European Medicines Agency (2019, December 04). Assessment Report on Ononis spinosa L., radix. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/herbal-report\/final-assessment-report-ononis-spinosa-l-radix_en.pdf."},{"key":"ref_15","unstructured":"European Medicines Agency (2019, December 04). Assessment Report on Solidago virgaurea L., herba. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/herbal-report\/assessment-report-solidago-virgaurea-l-herba_en.pdf."},{"key":"ref_16","first-page":"S1","article-title":"Cytoprotective and antiadhesive effects of aqueous leaf extract from Orthosiphon aristatus against uropathogenic E. coli","volume":"81","author":"Sarshar","year":"2016","journal-title":"Planta Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phymed.2017.02.009","article-title":"Aqueous extract from Orthosiphon stamineus leaves prevents bladder and kidney infection in mice","volume":"28","author":"Sarshar","year":"2017","journal-title":"Phytomedicine"},{"key":"ref_18","first-page":"39","article-title":"Therapie unkomplizierter Harnwegsinfektionen mit einem pflanzlichen Aquaretikum: Ergebnisse einer offenen Verlaufsstudie","volume":"38","author":"Fischer","year":"1998","journal-title":"Der Kassenarzt."},{"key":"ref_19","first-page":"863","article-title":"Wirksamkeit einer Phytotherapeutikakombination bei Harnwegsinfekten","volume":"11","author":"Fischer","year":"1994","journal-title":"Der Allgemeinarzt."},{"key":"ref_20","unstructured":"EMA (2019, December 04). Guideline on the Evaluation of Medicinal Products Indicated for Treatment of Bacterial Infections, Rev 3 Draft. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/draft-guideline-evaluation-medicinal-products-indicated-treatment-bacterial-infections-revision-3_en.pdf."},{"key":"ref_21","unstructured":"FDA (2019, December 04). Uncomplicated Urinary Tract Infections\u2014Developing Drugs for Treatment. Guidance for Industry, Available online: https:\/\/www.fda.gov\/media\/129531\/download."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Alidjanov, J.F., Naber, K.G., Abdufattaev, U.A., Pilatz, A., and Wagenlehner, F.M.E. (2018). Reevaluation of the Acute Cystitis Symptom Score, a Self-Reporting Questionnaire. Part I. Development, Diagnosis and Differential Diagnosis. Antibiotics, 7.","DOI":"10.3390\/antibiotics7010006"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Alidjanov, J.F., Naber, K.G., Abdufattaev, U.A., Pilatz, A., and Wagenlehner, F.M. (2018). Reevaluation of the Acute Cystitis Symptom Score, a Self-Reporting Questionnaire. Part II. Patient-Reported Outcome Assessment. Antibiotics, 7.","DOI":"10.3390\/antibiotics7020043"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Alidjanov, J.F., Naber, K.G., Pilatz, A., Radzhabov, A., Zamuddinov, M., Magyar, A., Tenke, P., and Wagenlehner, F.M. (2019). Evaluation of the draft guidelines proposed by EMA and FDA for the clinical diagnosis of acute uncomplicated cystitis in women. World J. Urol.","DOI":"10.1016\/S1569-9056(19)30029-6"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Alidjanov, J.F., Naber, K.G., Pilatz, A., Radzhabov, A., Zamuddinov, M., Magyar, A., Tenke, P., and Wagenlehner, F.M. (2019). Additional assessment of Acute Cystitis Symptom Score questionnaire for patient-reported outcome measure in female patients with acute uncomplicated cystitis: Part II. World J. Urol.","DOI":"10.1007\/s00345-019-02948-8"},{"key":"ref_26","first-page":"55561","article-title":"Preliminary Clinical Validation of the English Language Version of the Acute Cystitis Symptom Score","volume":"1","author":"Alidjanov","year":"2017","journal-title":"JOJ Urol. Nephron."},{"key":"ref_27","unstructured":"Diggle, P.J., Heagerty, P., Liang, K., and Zeger, S.L. (2005). Analysis of Longitudinal Data, Oxford University Press. [2nd ed.]."},{"key":"ref_28","unstructured":"Pocock, S.J. (1991). Clinical Trials, A Practical Approach, Wiley."},{"key":"ref_29","unstructured":"(2019, December 04). The R Project for Statistical Computing. Version 3.3.2. Available online: https:\/\/www.r-project.org\/."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/8\/4\/256\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:18Z","timestamp":1760190018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/8\/4\/256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,7]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["antibiotics8040256"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics8040256","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,7]]}}}