{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:45:48Z","timestamp":1791773148359,"version":"4.3.4"},"reference-count":28,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute pyelonephritis (AP) and complicated urinary tract infections (cUTIs) are pooled in randomized controlled trials (RCTs) of antibiotics. We assessed whether outcomes differ between subtypes and which component of the composite endpoint drives any difference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Across 10 registrational RCTs, we estimated the AP-versus-cUTI treatment effect on the composite primary endpoint (clinical cure plus microbiologic eradication at test of cure [TOC]) using random-effects risk ratios, risk difference, odds ratio, and leave-one-out sensitivity analyses. Between-arm differences in the composite and components were correlated across trials; operative definitions and stratified-reporting practices were extracted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 5971 patients (3393 AP; 2578 other cUTI), AP showed higher cure at TOC (pooled risk ratio = 1.12; 95% CI 1.03\u20131.23; I2 = 82%; 95% prediction interval 0.86\u20131.46). Between-arm differences in the composite correlated strongly with those in microbiologic eradication (r = 0.98) but weakly with those in clinical cure (r = 0.30). In the single trial with subtype-stratified components (ADAPT-PO), the AP-versus-cUTI gap was larger in microbiologic eradication (+15.6 percentage point [pp]) than in clinical response (+3.5 pp); whether this generalizes to the remaining 9 trials could not be tested. Risk of bias was overall some concerns in 9\/10 trials, mostly for missing outcome data and selection of the reported result.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Acute pyelonephritis achieved higher cure rates at TOC than other cUTIs. Heterogeneity in operative AP\/cUTI definitions and limited stratified reporting of component outcomes reduce interstudy comparability. Trials should harmonize definitions, prespecify stratification by subtype, and disclose clinical and microbiologic outcomes separately.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag516","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:42:35Z","timestamp":1787658155000},"source":"Crossref","is-referenced-by-count":0,"title":["Does Acute Pyelonephritis Skew Outcomes in Registrational Trials of Novel Antibiotics for Complicated Urinary Tract Infections? A Systematic Review and Meta-analysis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-2220","authenticated-orcid":false,"given":"Giovanni","family":"Mori","sequence":"first","affiliation":[{"name":"Infectious Diseases Unit, Santa Chiara Regional and Teaching Hospital, Provincial Health Care Agency (APSS) , Trento ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2423-2933","authenticated-orcid":false,"given":"Tommaso","family":"Ceccato","sequence":"additional","affiliation":[{"name":"Urology Division, Santa Chiara Regional and Teaching Hospital, Provincial Health Care Agency (APSS) , Trento ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6874-2904","authenticated-orcid":false,"given":"Simone","family":"Botti","sequence":"additional","affiliation":[{"name":"Urology Division, Santa Chiara Regional and Teaching Hospital, Provincial Health Care Agency (APSS) , Trento ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2475-8732","authenticated-orcid":false,"given":"Simone","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Department of Medicine (DMED), Infectious Diseases Clinic, University of Udine , Udine ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Tascini","sequence":"additional","affiliation":[{"name":"Department of Medicine (DMED), Infectious Diseases Clinic, University of Udine , Udine ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Stefani","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania , Catania ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4674-4772","authenticated-orcid":false,"given":"Massimiliano","family":"Lanzafame","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Santa Chiara Regional and Teaching Hospital, Provincial Health Care Agency (APSS) , Trento ,","place":["Italy"]},{"name":"Interdepartmental Centre of Medical Sciences (CISMed), University of Trento , Trento ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Truls Erik Bjerklund","family":"Johansen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, University of Oslo , Oslo ,","place":["Norway"]},{"name":"Department of Urology, Oslo University Hospital , Oslo ,","place":["Norway"]},{"name":"Institute of Clinical Medicine, University of Aarhus , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-3526","authenticated-orcid":false,"given":"Tommaso","family":"Cai","sequence":"additional","affiliation":[{"name":"Urology Division, Santa Chiara Regional and Teaching Hospital, Provincial Health Care Agency (APSS) , Trento ,","place":["Italy"]},{"name":"Interdepartmental Centre of Medical Sciences (CISMed), University of Trento , Trento ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"2026101122312332700_ciag516-B1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.3390\/antibiotics14080813","article-title":"The current landscape of antibiotic use and antimicrobial resistance in Japan: focusing on common infections including uncomplicated urinary tract infection and 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infections","volume":"30","author":"Kulchavenya","year":"2020","journal-title":"Curr Opin Urol"},{"key":"2026101122312332700_ciag516-B5","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.cmi.2022.05.016","article-title":"Antibiotic management of urinary tract infections in the post-antibiotic era: a narrative review highlighting diagnostic and antimicrobial stewardship","volume":"29","author":"Abbott","year":"2023","journal-title":"Clin Microbiol Infect"},{"key":"2026101122312332700_ciag516-B6","doi-asserted-by":"crossref","first-page":"e605","DOI":"10.1016\/S1473-3099(25)00142-2","article-title":"Consensus position statement on advancing the classification of patients and tests of cure in studies of antibiotic treatment of complicated urinary tract infections","volume":"25","author":"Bjerklund Johansen","year":"2025","journal-title":"Lancet Infect 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(ASPECT-cUTI)","volume":"385","author":"Wagenlehner","year":"2015","journal-title":"Lancet"},{"key":"2026101122312332700_ciag516-B15","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1093\/cid\/ciw378","article-title":"Ceftazidime-avibactam versus doripenem for the treatment of complicated urinary tract infections, including acute pyelonephritis (RECAPTURE 1 and 2): results from two randomized, phase 3 trials","volume":"63","author":"Wagenlehner","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2026101122312332700_ciag516-B16","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2018.0438","article-title":"Effect of meropenem-vaborbactam vs piperacillin-tazobactam on clinical cure and microbial eradication in complicated urinary tract infection: the TANGO I randomized clinical 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pyelonephritis (ADAPT-PO): a randomized, double-blind, phase 3, non-inferiority trial","volume":"386","author":"Takase","year":"2022","journal-title":"N Engl J Med"},{"key":"2026101122312332700_ciag516-B23","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1093\/cid\/ciac704","article-title":"Sulopenem for the treatment of complicated urinary tract infections including pyelonephritis: a phase 3, randomized trial","volume":"76","author":"Dunne","year":"2023","journal-title":"Clin Infect Dis"},{"key":"2026101122312332700_ciag516-B24","author":"U.S. Food and Drug Administration, Center for Drug Evaluation and Research"},{"key":"2026101122312332700_ciag516-B25","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.cmi.2025.04.008","article-title":"Short vs long antibiotic treatment for pyelonephritis and complicated urinary tract infections: a living systematic review and meta-analysis of randomized controlled trials","volume":"31","author":"Zahavi","year":"2025","journal-title":"Clin Microbiol Infect"},{"key":"2026101122312332700_ciag516-B26","volume-title":"Pyelonephritis (acute): antimicrobial prescribing. 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