{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T09:32:59Z","timestamp":1763112779188,"version":"3.45.0"},"reference-count":40,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"OM Pharma SA\/CSL"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Management of acute episodes of lower urinary tract infection (LUTI) depends on whether they are sporadic or recurrent. We aimed to define factors that differentiate patients with acute sporadic cystitis (AC) from those with recurrent cystitis (RC) and thereby improve individualized care. Methods: We performed a post hoc analysis of prospectively collected data from the multinational GPIU.COM study. Female patients with an acute LUTI episode completed the Acute Cystitis Symptom Score (ACSS) and underwent a routine clinical and laboratory evaluation, including a physical examination, ultrasonography, urinalysis, and urine culture and antimicrobial susceptibility testing. Risk factors for recurrence were evaluated using the Lower Urinary Tract Infection Recurrence Risk (LUTIRE) nomogram and the ORENUC classification. Statistical analysis followed a robust stepwise approach. Significant variables were assessed by relative risk (RR), and logistic regression was used to estimate odds ratios (ORs). Model performance was evaluated using the area under the curve (AUC), the Hosmer\u2013Lemeshow test, variance inflation factor (VIF), and bootstrap sampling. Results: A total of 106 women were included (AC n = 50; RC n = 56). Patients with RC more frequently presented with a history of constipation, a severe impact of symptoms on daily activities, multiple uropathogens, and trace proteinuria. Pyuria was inversely associated with RC. Logistic regression identified chronic constipation, severe impact of symptoms on daily activities, and multiple uropathogens as independent predictors of RC. Three predictive models showed consistent discrimination between AC and RC (AUC = 0.80, 0.82, and 0.84). Conclusions: AC and RC showed notable differences in certain symptom profiles, quality of life, urinalysis, and microbiological findings. Combining high-value predictors from LUTIRE and ORENUC into a comprehensive prognostic algorithm could improve assessment of recurrence risk. A refined classification of LUTIs with recurrence grading is warranted to guide decision-making and prevention strategies.<\/jats:p>","DOI":"10.3390\/diagnostics15222885","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T09:06:36Z","timestamp":1763111196000},"page":"2885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Risk Factors in Patients with Recurrent Cystitis May Improve Individualized Management"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2531-4877","authenticated-orcid":false,"given":"Jakhongir F.","family":"Alidjanov","sequence":"first","affiliation":[{"name":"Scientific Team of the Acute Cystitis Symptom Score, Medical Biostatistics and Data Science, 90449 Nuremberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-8045","authenticated-orcid":false,"given":"Ulugbek A.","family":"Khudaybergenov","sequence":"additional","affiliation":[{"name":"Department of Urology, Tashkent State Medical University, Tashkent 100100, Uzbekistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2174-5426","authenticated-orcid":false,"given":"Khurshid B.","family":"Khudayberdiev","sequence":"additional","affiliation":[{"name":"Department of Urology, Tashkent State Medical University, Tashkent 100100, Uzbekistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0882-690X","authenticated-orcid":false,"given":"Jennifer","family":"Kranz","sequence":"additional","affiliation":[{"name":"Department of Urology and Pediatric Urology, University Clinic of Aachen, 52074 Aachen, Germany"},{"name":"Department of Urology and Kidney Transplantation, Martin-Luther-University, 06097 Halle, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3409-8654","authenticated-orcid":false,"given":"Laila","family":"Schneidewind","sequence":"additional","affiliation":[{"name":"Department of Urology, Inselspital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-2402","authenticated-orcid":false,"given":"Fabian P.","family":"Stangl","sequence":"additional","affiliation":[{"name":"Department of Urology, Inselspital, University of Bern, 3010 Bern, Switzerland"},{"name":"Department of Urology, Faculty of Medicine, Medical Center-University of Freiburg, 79106 Freiburg, Germany"},{"name":"Department of Urology and Andrology, Salzburg University Hospital, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3626-8669","authenticated-orcid":false,"given":"Jos\u00e9","family":"Medina-Polo","sequence":"additional","affiliation":[{"name":"Urology Department, Hospital Universitario 12 de Octubre Imas12, 28041 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8072-1841","authenticated-orcid":false,"given":"Adrian","family":"Pilatz","sequence":"additional","affiliation":[{"name":"Department of Urology, Andrology and Pediatric Urology, Justus-Liebig University of Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-3526","authenticated-orcid":false,"given":"Tommaso","family":"Cai","sequence":"additional","affiliation":[{"name":"Interdepartmental Centre of Medical Sciences (CISMed), University of Trento, 38122 Trento, Italy"},{"name":"Urology Division (APSS), Provincial Health Care Agency, Santa Chiara Regional and Teaching Hospital, 38122 Trento, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1304-5403","authenticated-orcid":false,"given":"Kurt G.","family":"Naber","sequence":"additional","affiliation":[{"name":"Department of Urology, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2909-0797","authenticated-orcid":false,"given":"Florian M.","family":"Wagenlehner","sequence":"additional","affiliation":[{"name":"Department of Urology, Andrology and Pediatric Urology, Justus-Liebig University of Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3490-6460","authenticated-orcid":false,"given":"Truls E.","family":"Bjerklund Johansen","sequence":"additional","affiliation":[{"name":"Department of Urology, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway"},{"name":"Institute of Clinical Medicine, University of Aarhus, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"ref_1","unstructured":"Bonkat, G., Kranz, J., Cai, T., Greelings, S.E., K\u00f6ves, B., Pilatz, A., Medina-Polo, J., Schneidewind, L., Schubert, S., and Veeratterapillay, R. (2025). EAU Guidelines on Urological Infections. EAU Guidelines. Edn., Proceedings of the EAU Annual Congress, Madrid, Spain, 21\u201324 March 2025, EAU Guidelines Office."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5S","DOI":"10.1016\/S0002-9343(02)01054-9","article-title":"Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs","volume":"113","author":"Foxman","year":"2002","journal-title":"Am. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ackerman, A.L., Bradley, M., D\u2019Anci, K.E., Hickling, D., Kim, S.K., and Kirkby, E. (2025). Updates to Recurrent Uncomplicated Urinary Tract Infections in Women: AUA\/CUA\/SUFU Guideline (2025). J. Urol., 101097ju0000000000004723.","DOI":"10.1097\/JU.0000000000004723"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1344","DOI":"10.1093\/infdis\/jiae233","article-title":"Antibiotic Resistance of Urinary Tract Infection Recurrences in a Large Integrated US Healthcare System","volume":"230","author":"Ku","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1177\/08971900221128851","article-title":"Delayed and Non-Antibiotic Therapy for Urinary Tract Infections: A Literature Review","volume":"37","author":"Midby","year":"2024","journal-title":"J. Pharm. Pract. Res."},{"key":"ref_6","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_7","first-page":"Doc01","article-title":"Therapeutic strategies for uncomplicated cystitis in women","volume":"12","author":"Naber","year":"2024","journal-title":"GMS Infect. Dis."},{"key":"ref_8","first-page":"10","article-title":"Are there alternatives to antimicrobial therapy and prophylaxis of uncomplicated urinary tract infections?","volume":"5\u20138","author":"Naber","year":"2014","journal-title":"Urologiia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1001\/jamainternmed.2024.0264","article-title":"d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial","volume":"184","author":"Hayward","year":"2024","journal-title":"JAMA Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1093\/oxfordjournals.aje.a010170","article-title":"Risk factors for second urinary tract infection among college women","volume":"151","author":"Foxman","year":"2000","journal-title":"Am. J. Epidemiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1111\/iju.12453","article-title":"Development and validation of a nomogram predicting recurrence risk in women with symptomatic urinary tract infection","volume":"21","author":"Cai","year":"2014","journal-title":"Int. J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ijantimicag.2011.09.009","article-title":"Critical review of current definitions of urinary tract infections and proposal of an EAU\/ESIU classification system","volume":"38","author":"Johansen","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1101","DOI":"10.1093\/infdis\/jiae331","article-title":"Risk Factors for Recurrent Urinary Tract Infections Among Women in a Large Integrated Health Care Organization in the United States","volume":"230","author":"Ackerson","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Soric Hosman, I., Cvitkovic Roic, A., and Lamot, L. (2022). A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection. Front. Med., 9.","DOI":"10.3389\/fmed.2022.931717"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105057","DOI":"10.1016\/j.cmicom.2024.105057","article-title":"Immunity to urinary tract infection: What the clinician should know","volume":"1","author":"Calin","year":"2024","journal-title":"CMI Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/QCO.0000000000000127","article-title":"Innate immunity and genetic determinants of urinary tract infection susceptibility","volume":"28","author":"Godaly","year":"2015","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hou, Y., Lv, Z., Hu, Q., Zhu, A., and Niu, H. (2025). The immune mechanisms of the urinary tract against infections. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1540149"},{"key":"ref_18","unstructured":"European Parliament and Council of the European Union (2001). Directive 2001\/20\/EC of 4 April 2001 on the Approximation of the Laws, Regulations and Administrative Provisions of the Member States Relating to the Implementation of Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for Human Use, European Parliament and Council of the European Union."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1007\/s00192-021-04864-1","article-title":"Linguistic and clinical validation of the acute cystitis symptom score in German-speaking Swiss women with acute cystitis","volume":"32","author":"Alidjanov","year":"2021","journal-title":"Int. Urogynecol. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1007\/s00120-015-3873-5","article-title":"German validation of the Acute Cystitis Symptom Score","volume":"54","author":"Alidjanov","year":"2015","journal-title":"Urologe A"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3109\/07853890109002087","article-title":"EQ-5D: A measure of health status from the EuroQol Group","volume":"33","author":"Rabin","year":"2001","journal-title":"Ann. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e20173068","DOI":"10.1542\/peds.2017-3068","article-title":"Accuracy of the Urinalysis for Urinary Tract Infections in Febrile Infants 60 Days and Younger","volume":"141","author":"Tzimenatos","year":"2018","journal-title":"Pediatrics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_24","unstructured":"(2025, May 08). European Committee on Antimicrobial Susceptibility Testing (EUCAST), Expert Rules and Expected Phenotypes. Available online: https:\/\/www.eucast.org\/expert_rules_and_expected_phenotypes."},{"key":"ref_25","first-page":"14","article-title":"Sample size calculation in medical studies","volume":"6","author":"Pourhoseingholi","year":"2013","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"ref_26","unstructured":"R Core Team (2017). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/biomet\/52.3-4.591","article-title":"An analysis of variance test for normality (complete samples)","volume":"52","author":"Shapiro","year":"1965","journal-title":"Biometrika"},{"key":"ref_28","unstructured":"Olkin, I., and Hotelling, H. (1960). Robust tests for equality of variances. Contributions to Probability and Statistics; Essays in Honor of Harold Hotelling, Stanford University Press."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2307\/2331554","article-title":"The Probable Error of a Mean","volume":"6","author":"Student","year":"1908","journal-title":"Biometrika"},{"key":"ref_30","first-page":"28","article-title":"The generalisation of Student\u2019s problems when several different population variances are involved","volume":"34","author":"Welch","year":"1947","journal-title":"Biometrika"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2307\/3001968","article-title":"Individual Comparisons by Ranking Methods","volume":"1","author":"Wilcoxon","year":"1945","journal-title":"Biom. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2307\/2340521","article-title":"On the Interpretation of \u03c72 from Contingency Tables, and the Calculation of P","volume":"85","author":"Fisher","year":"1922","journal-title":"J. R. Stat. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/14786440009463897","article-title":"On the criterion that a given system of deviations from the probable in the case of a correlated system of variables is such that it can be reasonably supposed to have arisen from random sampling","volume":"50","author":"Pearson","year":"1900","journal-title":"Lond. Edinb. Dublin Philos. Mag. J. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1017\/S0080456800012163","article-title":"The Correlation between Relatives on the Supposition of Mendelian Inheritance","volume":"52","author":"Fisher","year":"1919","journal-title":"Trans. R. Soc. Edinb."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1098\/rspl.1895.0041","article-title":"Note on Regression and Inheritance in the Case of Two Parents","volume":"58","author":"Pearson","year":"1895","journal-title":"Proc. R. Soc. Lond."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1002\/jrsm.1460","article-title":"Zero-cell corrections in random-effects meta-analyses","volume":"11","author":"Weber","year":"2020","journal-title":"Res. Synth. Methods"},{"key":"ref_37","unstructured":"van der Heijden, A.G., Bruins, H.M., Carrion, A., Cathomas, R., Comp\u00e9rat, E.M., Dimitropoulos, K., Efstathiou, J.A., Fietkau, R., Lorch, A., and Mariappan, P. (2025). EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. EAU Guidelines. Edn., Proceedings of the EAU Annual Congress, Madrid, Spain, 21\u201324 March 2025, EAU Guidelines Office."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"James, G., Witten, D., Hastie, T., and Tibshirani, R. (2013). Resampling Methods. An Introduction to Statistical Learning: With Applications in R, Springer Texts in Statistics, Springer.","DOI":"10.1007\/978-1-4614-7138-7"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Alidjanov, J.F., Naber, K.G., Pilatz, A., and Wagenlehner, F.M. (2020). Validation of the American English Acute Cystitis Symptom Score. Antibiotics, 9.","DOI":"10.20944\/preprints202011.0484.v1"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Radzhabov, A., Zamuddinov, M., Alidjanov, J.F., Pilatz, A., Wagenlehner, F.M., and Naber, K.G. (2023). Linguistic and Clinical Validation of the Tajik Acute Cystitis Symptom Score for Diagnosis and Patient-Reported Outcome in Acute Uncomplicated Cystitis. Medicina, 59.","DOI":"10.3390\/medicina59091549"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/22\/2885\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T09:28:37Z","timestamp":1763112517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/22\/2885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,14]]},"references-count":40,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["diagnostics15222885"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15222885","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,14]]}}}