{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:38:06Z","timestamp":1792600686335,"version":"4.5.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001794","name":"University of Queensland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100030599","name":"Henderson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030599","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Singapore's National Medical Research Council"},{"name":"NHMRC Early Career Fellowship","award":["GNT1157530"],"award-info":[{"award-number":["GNT1157530"]}]},{"name":"Emerging Leadership Fellowship","award":["GNT20338510"],"award-info":[{"award-number":["GNT20338510"]}]},{"name":"National Medical Research Council of Singapore","award":["MOH-CSAINV25JAN-0005"],"award-info":[{"award-number":["MOH-CSAINV25JAN-0005"]}]}],"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>Gram-negative bacterial bloodstream infections (BSIs) cause substantial mortality and morbidity. The GAME CHANGER trial compared cefiderocol with standard of care (SOC) for Gram-negative BSIs, with 14-day all-cause mortality (ACM) as the primary endpoint. We evaluated cefiderocol versus SOC integrating efficacy and safety outcomes using desirability of outcome ranking (DOOR) and generalized pairwise comparisons (GPC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Composite endpoints were prespecified before data review. The DOOR endpoint included treatment failure, infectious complications, serious adverse events, and 90-day ACM, with functional improvement as a tiebreaker. The GPC approach included ACM at 30 days, clinical failure, serious adverse events, functional improvement, and hospitalization duration. Analyses were conducted in the main population and carbapenem-resistant subset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The DOOR composite in the main population resulted in a probability of a more desirable outcome with cefiderocol of 50.4% (95% confidence interval [CI], 45.6\u201355.1). The analysis with GPC resulted in a win ratio and win odds of 1.04 (95% CI, 0.85\u20131.28) and net treatment benefit of 2.1% (95% CI, \u22128.0 to 12.2). In the carbapenem-resistant subset, the DOOR probability with cefiderocol was 46.8% (95% CI, 37.4\u201356.1). The analysis with GPC resulted in a win ratio and win odds of 0.90 (95% CI, 0.60\u20131.34) and net treatment benefit of \u22125.4% (95% CI, \u221225.3 to 14.5).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In adults with Gram-negative bacterial BSIs, cefiderocol was not superior to SOC based on DOOR or GPC analyses in both the main population and carbapenem-resistant subset. Integrating efficacy, safety, and functional outcomes using these approaches provides a more comprehensive assessment than mortality alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciag538","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:19:12Z","timestamp":1788520752000},"source":"Crossref","is-referenced-by-count":0,"title":["A Randomized Controlled Trial of Cefiderocol Versus Standard Therapy for Gram-negative Bacterial Bloodstream Infections: Benefit and Risk Assessment Using Desirability of Outcome Ranking and Generalized Pairwise Comparisons"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2427-6082","authenticated-orcid":false,"given":"Melissa J","family":"Hardy","sequence":"first","affiliation":[{"name":"The University of Queensland, Faculty of Health, Medicine and Behavioural Sciences, Frazer Institute, The University of Queensland , Brisbane, QLD ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2895-0345","authenticated-orcid":false,"given":"Patrick N A","family":"Harris","sequence":"additional","affiliation":[{"name":"The University of Queensland, Faculty of Health, Medicine and Behavioural Sciences, Frazer Institute, The University of Queensland , Brisbane, QLD ,","place":["Australia"]},{"name":"Department of Infectious Disease, Royal Brisbane and Women's Hospital , Brisbane, QLD ,","place":["Australia"]},{"name":"Pathology Queensland, Central Microbiology, Royal Brisbane and Women's Hospital , Brisbane, QLD ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0216-9550","authenticated-orcid":false,"given":"Yin","family":"Mo","sequence":"additional","affiliation":[{"name":"ADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore ,","place":["Singapore"]},{"name":"Yong Loo Lin School of Medicine, National University of Singapore ,","place":["Singapore"]},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford , Oxford ,","place":["United Kingdom"]},{"name":"Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University , Bangkok ,","place":["Thailand"]},{"name":"Division of Infectious Diseases, University Medicine Cluster, National University Hospital ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D","family":"Chatfield","sequence":"additional","affiliation":[{"name":"The University of Queensland, Faculty of Health, Medicine and Behavioural Sciences, Frazer Institute, The University of Queensland , Brisbane, QLD 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