{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:22:15Z","timestamp":1792624935367,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T00:00:00Z","timestamp":1581552000000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["1KL2TR002554"],"award-info":[{"award-number":["1KL2TR002554"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To identify risk stratification biomarkers to enrich for the subset of <jats:italic>Staphylococcus aureus<\/jats:italic> bacteraemia patients who develop deep\u2010seated tissue infections with high morbidity and mortality to guide clinical trial enrolment and clinical management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the prognostic value of eight biomarkers for persistent bacteraemia, mortality and endovascular infection foci in a validation cohort of 160 patients with <jats:italic>S.\u00a0aureus<\/jats:italic> bacteraemia enrolled consecutively over 3\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High levels of IL\u201017A, IL\u201010 or soluble E\u2010selectin at bacteraemia diagnosis correlated with the duration of positive blood cultures. When thresholds defined in an independent cohort were applied, these biomarkers were robust predictors of persistent bacteraemia or endovascular infection. High serum levels of IL\u201017A and IL\u201010 often preceded the radiographic diagnosis of infective endocarditis, suggesting potential utility for prioritising diagnostic radiographic imaging. High IL\u20108 was prognostic for all\u2010cause mortality, while IL\u201017A and IL\u201010 were superior to clinical metrics in discriminating between attributable mortality and non\u2010attributable mortality. High IL\u201017A and IL\u201010 identified more patients who developed microbiological failure or mortality than were identified by infective endocarditis diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These biomarkers offer potential utility to identify patients at risk of persistent bacteraemia to guide diagnostic imaging and clinical management. Low biomarker levels could be used to rule out the need for more invasive TEE imaging in patients at lower risk of infective endocarditis. These biomarkers could enable clinical trials by enriching for patients with the greatest need for novel therapies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1110","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T23:50:16Z","timestamp":1581637816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Risk stratification biomarkers for <i>Staphylococcus aureus<\/i> bacteraemia"],"prefix":"10.1002","volume":"9","author":[{"given":"Yi","family":"Cao","sequence":"first","affiliation":[{"name":"Bioinformatics and Computational Biology Genentech, Inc. South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessander O","family":"Guimaraes","sequence":"additional","affiliation":[{"name":"Biomarker Discovery Genentech, Inc. South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melicent C","family":"Peck","sequence":"additional","affiliation":[{"name":"Clinical Sciences Genentech, Inc. South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Mayba","sequence":"additional","affiliation":[{"name":"Bioinformatics and Computational Biology Genentech, Inc. South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Ruffin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu","family":"Hong","sequence":"additional","affiliation":[{"name":"BioAnalytical Sciences Genentech, Inc. South San Francisco CA USA"},{"name":"BioAnalysis, Immune\u2010Onc Therapeutics Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Carrasco\u2010Triguero","sequence":"additional","affiliation":[{"name":"BioAnalytical Sciences Genentech, Inc. South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Vance G","family":"Fowler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey A","family":"Maskarinec","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Duke University Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8189-8822","authenticated-orcid":false,"given":"Carrie M","family":"Rosenberger","sequence":"additional","affiliation":[{"name":"Biomarker Discovery Genentech, Inc. South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy739"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007667"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0147-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-014-0580-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis552"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000001465"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix157"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.59"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.09.093"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2008.603"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.05022-11"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-016-2598-8"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1093\/cid\/ciz257","article-title":"Defining the breakpoint duration of Staphylococcus aureus bacteremia predictive of poor outcomes","volume":"70","author":"Minejima E","year":"2019","journal-title":"Clin Infect Dis"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02483-18"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz686"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz112"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/515076"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2018.04.039"},{"key":"e_1_2_7_20_1","first-page":"1041","article-title":"Patient characteristics, management, and predictors of outcome from severe community\u2010onset Staphylococcal sepsis in Northeast Thailand: a prospective multicenter study","volume":"96","author":"West TE","year":"2017","journal-title":"Am J Trop Med Hyg"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13266"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201611-2307OC"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200801-131OC"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01902-17"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.09.028"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200439"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc10515"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01061-15"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40891"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01491-14"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz090"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz126"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/520088"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018673"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir389"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2014.166"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-018-03464-0"},{"key":"e_1_2_7_38_1","first-page":"w14482","article-title":"Value of the pitt bacteraemia score to predict short\u2010term mortality in Staphylococcus aureus bloodstream infection: a validation study","volume":"147","author":"Roth JA","year":"2017","journal-title":"Swiss Med Wkly"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy210.898"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq146"},{"key":"e_1_2_7_41_1","volume-title":"R: A language and environment for statistical computing","author":"R Core Team (R Foundation for Statistical Computing)","year":"2013"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_7_44_1","first-page":"18","article-title":"Classification and regression by randomforest","volume":"2","author":"Liaw A","year":"2002","journal-title":"R News"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcti2.1110","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1110","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1110","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:21:01Z","timestamp":1694020861000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1002\/cti2.1110"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1110","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"2019-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1110"}}