{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:15:01Z","timestamp":1791814501997,"version":"4.3.4"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Iterum Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sulopenem is a thiopenem antibiotic being developed for the treatment of multidrug-resistant infections. The availability of both intravenous (IV) and oral formulations will facilitate earlier hospital discharge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hospitalized adults with pyuria, bacteriuria, and signs and symptoms of complicated urinary tract infection (cUTI) were randomized to 5 days of IV sulopenem followed by oral sulopenem etzadroxil\/probenecid or 5 days of IV ertapenem followed by oral ciprofloxacin or amoxicillin-clavulanate, depending on uropathogen susceptibility. The primary end point was overall combined clinical and microbiologic response at the test-of-cure visit (day 21).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 1392 treated patients, 444 and 440 treated with sulopenem and ertapenem, respectively, had a positive baseline urine culture and were eligible for the primary ef\ufb01cacy analyses. Extended-spectrum \u03b2-lactamase-producing organisms were identified in 26.6% of patients and fluoroquinolone-nonsusceptible pathogens in 38.6%. For the primary end point, noninferiority of sulopenem to the comparator regimen was not demonstrated, 67.8% vs 73.9% (difference, \u22126.1%; 95% confidence interval, \u221212.0 to \u2212.1%). The difference was driven by a lower rate of asymptomatic bacteriuria in the subgroup of ertapenem-treated patients who stepped down to ciprofloxacin. No substantial difference in overall response was observed at any other time point. Both IV and oral formulations of sulopenem were well-tolerated and compared favorably to the comparator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sulopenem followed by oral sulopenem-etzadroxil\/probenecid was not noninferior to ertapenem followed by oral step-down therapy for the treatment of cUTIs, driven by a lower rate of asymptomatic bacteriuria in those who received ciprofloxacin. Both formulations of sulopenem were well-tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>NCT03357614.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciac704","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T16:25:30Z","timestamp":1661790330000},"page":"78-88","source":"Crossref","is-referenced-by-count":51,"title":["Sulopenem for the Treatment of Complicated Urinary Tract Infections Including Pyelonephritis: A Phase 3, Randomized Trial"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6186-5196","authenticated-orcid":false,"given":"Michael W","family":"Dunne","sequence":"first","affiliation":[{"name":"Iterum Therapeutics , Old Saybrook, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven I","family":"Aronin","sequence":"additional","affiliation":[{"name":"Iterum Therapeutics , Old Saybrook, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita F","family":"Das","sequence":"additional","affiliation":[{"name":"Das Statistical Consulting , Guerneville, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Akinapelli","sequence":"additional","affiliation":[{"name":"Takeda Pharmaceuticals , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Breen","sequence":"additional","affiliation":[{"name":"Iterum Therapeutics , Old Saybrook, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T","family":"Zelasky","sequence":"additional","affiliation":[{"name":"Johnson & Johnson , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailaja","family":"Puttagunta","sequence":"additional","affiliation":[{"name":"Iterum Therapeutics , Old Saybrook, Connecticut , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,7]]},"reference":[{"key":"2023010809022296400_ciac704-B1","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1017\/ice.2016.174","article-title":"Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011\u20132014","volume":"37","author":"Weiner","year":"2016","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2023010809022296400_ciac704-B2","volume-title":"Antibiotic resistance threats in the United States 2019","author":"US Department of Health and Human Services","year":"2019"},{"key":"2023010809022296400_ciac704-B3","author":"European Centre for Disease Prevention and Control","year":"2019"},{"key":"2023010809022296400_ciac704-B4","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0220265","article-title":"The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017","volume":"14","author":"Critchley","year":"2019","journal-title":"PLoS One"},{"key":"2023010809022296400_ciac704-B5","first-page":"e01832","article-title":"In vitro activity of sulopenem, an oral penem, against urinary isolates of Escherichia coli","volume":"63","author":"Karlowsky","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2023010809022296400_ciac704-B6","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1001\/jama.2012.80","article-title":"Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis. 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