{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T21:34:36Z","timestamp":1785447276561,"version":"3.56.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,11,4]],"date-time":"2023-11-04T00:00:00Z","timestamp":1699056000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Polish"},{"DOI":"10.13039\/501100004569","name":"Ministry of Science and Higher Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Current US Food and Administration (FDA) guidance recommends that the primary efficacy endpoint for uncomplicated urinary tract infection (uUTI) clinical trials be a composite of clinical and microbiological responses. We applied these criteria to a previous clinical trial to determine the impact on treatment outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a patient-level reanalysis of a randomized clinical trial of nitrofurantoin versus fosfomycin for treatment of uUTI in nonpregnant adult women. Women were included in the reanalysis if they had 2 or more signs\/symptoms of uUTI and a single bacterial species isolated from baseline urine culture at \u2265105\u2005colony-forming units (CFU)\/mL. The applied primary efficacy endpoint\u2014therapeutic response\u2014required both clinical resolution of signs\/symptoms and reduction of the infecting bacterial pathogen to &amp;lt;103\u2005CFU\/mL at day 14 post\u2013treatment completion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Two hundred eleven of 513 (41%) patients were eligible for inclusion in the reanalysis. Among these patients, 74% (76\/103) and 69% (75\/108) in the nitrofurantoin and fosfomycin groups, respectively, achieved clinical resolution by day 14. Similarly, 70% (72\/103) and 67% (72\/108) in each group achieved microbiological success at day 14. As such, 59% (61\/103) and 57% (62\/108) of women in each group met the primary efficacy endpoint\u2014therapeutic success\u2014at day 14. In comparison, 75% and 66% of patients in each group achieved clinical resolution at day 14 in the initial clinical trial.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Applying current FDA guidance resulted in lower composite efficacy rates than clinical resolution alone as observed in the initial clinical trial. This may limit the ability to compare antibiotic treatment effects between historical and future clinical trials.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofad557","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T06:34:21Z","timestamp":1699425261000},"source":"Crossref","is-referenced-by-count":4,"title":["Impact of the 2019 Food and Drug Administration Guidance for Uncomplicated Urinary Tract Infection on Treatment Response Rates: A Reanalysis of a Clinical Trial of Nitrofurantoin vs Fosfomycin"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8412-8113","authenticated-orcid":false,"given":"Rebecca","family":"Grant","sequence":"first","affiliation":[{"name":"Infection Control Programme, Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"B\u00fcchler","sequence":"additional","affiliation":[{"name":"Infection Control Programme, Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Flight","sequence":"additional","affiliation":[{"name":"Clinical Sciences, GSK , Brentford , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Huang","sequence":"additional","affiliation":[{"name":"Biostatistics, GSK , Collegeville, Pennsylvania , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo","family":"Ferrinho","sequence":"additional","affiliation":[{"name":"Global Medical Affairs , GSK, Brentford , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Janmohamed","sequence":"additional","affiliation":[{"name":"Clinical Sciences, GSK , Brentford , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruni","family":"Mulgirigama","sequence":"additional","affiliation":[{"name":"Global Medical Affairs , GSK, Brentford , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciek","family":"Godycki-Cwirko","sequence":"additional","affiliation":[{"name":"Centre for Family and Community Medicine, Faculty of Medical Sciences, Medical University of Lodz , Lodz , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Leibovici","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Beilinson Hospital , Petah Tikva , Israel"},{"name":"Faculty of Medicine, Tel-Aviv University , Ramat Aviv , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Huttner","sequence":"additional","affiliation":[{"name":"Center for Clinical Research, Geneva University Hospitals and Faculty of Medicine , University of Geneva, Geneva , Switzerland"},{"name":"Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine , University of Geneva, Geneva , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Harbarth","sequence":"additional","affiliation":[{"name":"Infection Control Programme, Geneva University Hospitals and Faculty of Medicine, University of Geneva , Geneva , Switzerland"},{"name":"Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine , University of Geneva, Geneva , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,4]]},"reference":[{"key":"2023113021485176100_ofad557-B1","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1093\/cid\/ciq257","article-title":"International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases","volume":"52","author":"Gupta","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2023113021485176100_ofad557-B2","article-title":"Global antimicrobial resistance and use surveillance system (GLASS) report.","author":"World Health Organization","year":"2021"},{"key":"2023113021485176100_ofad557-B3","article-title":"Assessing the health burden of infections with antibiotic-resistant bacteria in the EU\/EEA, 2016\u20132020: technical report","author":"European Centre for Disease Prevention and Control","year":"2022"},{"key":"2023113021485176100_ofad557-B4","article-title":"Antibiotic resistance threats in the United States.","author":"US Department of Health and Human Services Centers for Disease Control and Prevention","year":"2019"},{"key":"2023113021485176100_ofad557-B5","article-title":"Guidance for industry. Uncomplicated urinary tract infections: developing drugs for treatment.","author":"US Department of Health and Human Services Food and Drug Administration","year":"2019"},{"key":"2023113021485176100_ofad557-B6","article-title":"Guidance for industry. Uncomplicated urinary tract infections: developing antimicrobial drugs for treatment","author":"US Department of Health and Human Services Food and Drug Administration","year":"1998"},{"key":"2023113021485176100_ofad557-B7","article-title":"Guideline on the evaluation of medicinal products indicated for treatment of bacterial infections: European Medicines Agency.","author":"European Medicines Agency, Committee for Medicinal Products for Human Use","year":"2022"},{"key":"2023113021485176100_ofad557-B8","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1001\/jama.2018.3627","article-title":"Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women: a randomized clinical trial","volume":"319","author":"Huttner","year":"2018","journal-title":"JAMA"},{"key":"2023113021485176100_ofad557-B9","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.cmi.2017.04.004","article-title":"Women with symptoms of a urinary tract infection but a negative urine culture: PCR-based quantification of Escherichia coli suggests infection in most cases","volume":"23","author":"Heytens","year":"2017","journal-title":"Clin Microbiol Infect"},{"key":"2023113021485176100_ofad557-B10","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1093\/cid\/ciad010","article-title":"Discordant clinical and microbiological outcomes are associated with late clinical relapse in clinical trials for complicated urinary tract infections","volume":"76","author":"Kadry","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2023113021485176100_ofad557-B11","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jgar.2021.11.008","article-title":"A global perspective on improving patient care in uncomplicated urinary tract infection: expert consensus and practical guidance","volume":"28","author":"Wagenlehner","year":"2022","journal-title":"J Glob Antimicrob Resist"},{"key":"2023113021485176100_ofad557-B12","doi-asserted-by":"crossref","first-page":"ITC49","DOI":"10.7326\/AITC201710030","article-title":"Urinary tract infection","volume":"167","author":"Gupta","year":"2017","journal-title":"Ann Intern Med"},{"key":"2023113021485176100_ofad557-B13","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1086\/674848","article-title":"Evaluation of an antimicrobial stewardship approach to minimize overuse of antibiotics in patients with asymptomatic bacteriuria","volume":"35","author":"Kelley","year":"2014","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2023113021485176100_ofad557-B14","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1017\/ice.2016.199","article-title":"Impact of an antimicrobial stewardship care bundle to improve the management of patients with suspected or confirmed urinary tract infection","volume":"37","author":"Collins","year":"2016","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2023113021485176100_ofad557-B15","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1093\/jac\/dkv147","article-title":"Nitrofurantoin revisited: a systematic review and meta-analysis of controlled trials","volume":"70","author":"Huttner","year":"2015","journal-title":"J Antimicrob Chemother"},{"key":"2023113021485176100_ofad557-B16","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1159\/000512582","article-title":"The clinical efficacy of nitrofurantoin for treating uncomplicated urinary tract infection in adults: a systematic review of randomized control trials","volume":"105","author":"Porreca","year":"2021","journal-title":"Urol Int"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofad557\/52841632\/ofad557.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/10\/11\/ofad557\/53898716\/ofad557.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/10\/11\/ofad557\/53898716\/ofad557.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T21:49:23Z","timestamp":1701380963000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofad557\/7344688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,1]]},"references-count":16,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofad557","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,11]]},"published":{"date-parts":[[2023,11,1]]},"article-number":"ofad557"}}