{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:30:00Z","timestamp":1790562600467,"version":"4.1.0"},"reference-count":21,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basilea Pharmaceutica International Ltd., Allschwil, Switzerland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: In the US, 120,000 cases of Staphylococcus aureus bacteremia (SAB) occur annually. Apart from mortality, little is known about other unfavorable outcomes (UOs). We developed a multifaceted definition for UOs in SAB and examined their incidence and predictors. Methods: We conducted a multicenter (~300 hospitals) retrospective cohort study between 2020 and 2022 of adult hospitalized patients with at least one blood culture (BC) positive for S. aureus. UOs were any of the following: hospital mortality, antibiotic escalation, persistently positive BCs, prolonged post-infection length of stay (LOS), 30-day readmission, and disease worsening. We compared the group with UOs to favorable outcomes (FOs). Regression models identified predictors of UOs. Results: Among 4080 patients with SAB, 2427 (59.5%) experienced a UO, most commonly 30-day readmission (42.0%) and antibiotic escalation (37.7%). Those with UOs more frequently had septic shock at admission (5.7% vs. 1.2%), requiring the ICU (18.8% vs. 14.7%) and dialysis (4.4% vs. 1.9%) prior to SAB onset. Community-onset SAB predominated in both groups, with more complicated SAB in the UO group (39.8% vs. 22.3%). Vancomycin use was similar, while daptomycin was more common in the UO group (8.5% vs. 3.0%). Variables with the highest odds ratios predicting a UO were septic shock on admission (3.498, 95% CI 2.145, 5.704), empiric daptomycin (2.723, 95% CI 1.943, 3.821), and complicated SAB (2.476, 95% CI 2.047, 2.994). Conclusions: UOs occur frequently in the setting of SAB. A broader perspective exploring issues other than mortality demonstrates the substantial implications of SAB both for patients and healthcare systems. Select clinical variables are associated with UOs, some of which may not be modifiable.<\/jats:p>","DOI":"10.3390\/antibiotics14030326","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:03:59Z","timestamp":1742447039000},"page":"326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unfavorable Outcomes and Their Risk Factors in Hospitalized Patients with Staphylococcus aureus Bacteremia in the US: A Multicenter Retrospective Cohort Study, 2020\u20132022"],"prefix":"10.3390","volume":"14","author":[{"given":"Marya D.","family":"Zilberberg","sequence":"first","affiliation":[{"name":"EviMed Research Group, LLC, Goshen, MA 01032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian H.","family":"Nathanson","sequence":"additional","affiliation":[{"name":"OptiStatim, LLC, Longmeadow, MA 01106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7325-4257","authenticated-orcid":false,"given":"Rolf","family":"Wagenaar","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd., 4123 Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3773-5708","authenticated-orcid":false,"given":"Jan","family":"Posthumus","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd., 4123 Allschwil, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-8328","authenticated-orcid":false,"given":"Andrew F.","family":"Shorr","sequence":"additional","affiliation":[{"name":"Washington Hospital Center, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1001\/jama.298.15.1763","article-title":"Invasive methi-cillin-resistant Staphylococcus aureus infections in the United States","volume":"298","author":"Klevens","year":"2007","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.15585\/mmwr.mm6809e1","article-title":"Vital Signs:Epidemiology and Recent Trends in Methicillin-Resistant and in Methicillin-SusceptibleStaphylococcus aureusBloodstream Infections\u2014United States","volume":"68","author":"Kourtis","year":"2019","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1001\/jama.2010.1115","article-title":"Healthcare-associated Invasive MRSA Infections, 2005\u20132008","volume":"304","author":"Kallen","year":"2010","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1093\/cid\/ciae338","article-title":"Clinical Subphenotypes of Staphylococcus aureus Bacteremia","volume":"79","author":"Swets","year":"2024","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","unstructured":"US Department of Health and Human Services Office for Human Research Protections (2024, February 03). Human Subject Regulations Decision Charts, Available online: https:\/\/www.hhs.gov\/ohrp\/regulations-and-policy\/decision-charts\/index.html."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.chest.2018.12.024","article-title":"A novel algorithm to analyze epidemiology and outcomes of carbapenem resistance among patients with hospital-acquired and ventilator-associated pneumonia: A retrospective cohort study","volume":"155","author":"Zilberberg","year":"2019","journal-title":"Chest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1017\/ice.2018.166","article-title":"Development and validation of a bedside instrument to predict carbapenem resistance among gram-negative pathogens in complicated urinary tract infections","volume":"39","author":"Zilberberg","year":"2018","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"ofz504","DOI":"10.1093\/ofid\/ofz504","article-title":"Carbapenem Treatment and Outcomes Among Patients with Culture-Positive Complicated Intra-abdominal Infections in US Hospitals: A Retrospective Cohort Study","volume":"6","author":"Zilberberg","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Rothberg, M.B., Pekow, P.S., Priya, A., Zilberberg, M.D., Belforti, R., Skiest, D., Lagu, T., Higgins, T.L., and Lindenauer, P.K. (2014). Using Highly Detailed Administrative Data to Predict Pneumonia Mortality. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087382"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S107","DOI":"10.1017\/S0899823X00194073","article-title":"Outcomes of patients with healthcare-associated pneumonia: Worse disease or sicker patients?","volume":"35","author":"Rothberg","year":"2014","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1001\/jamasurg.2022.2761","article-title":"Association Between Time to Source Control in Sepsis and 90-Day Mortality","volume":"157","author":"Reitz","year":"2022","journal-title":"JAMA Surg."},{"key":"ref_12","unstructured":"Jiang, H.J., and Hensche, M.K. (2024, August 19). Characteristics of 30-Day All-Cause Hospital Readmissions, 2016\u20132020. HCUP Statistical Brief #304, Available online: www.hcup-us.ahrq.gov\/reports\/statbriefs\/sb304-readmissions-2016-2020.pdf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1093\/cid\/ciz123","article-title":"Methicillin-susceptible and Methicillin-resistant Staphylococcus aureus Bacteremia: Nationwide Estimates of 30-Day Readmission, In-hospital Mortality, Length of Stay, and Cost in the United States","volume":"69","author":"Inagaki","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e207750","DOI":"10.1001\/jamanetworkopen.2020.7750","article-title":"Assessment of the Accuracy of Using ICD-9 Diagnosis Codes to Identify Pneumonia Etiology in Patients Hospitalized with Pneumonia","volume":"3","author":"Higgins","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.cmi.2022.03.015","article-title":"Staphylococcus aureus bacteraemia mortality: A systematic review and meta-analysis","volume":"28","author":"Bai","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1128\/CMR.05022-11","article-title":"Predictors of Mortality in Staphylococcus aureus Bacteremia","volume":"25","author":"Jensen","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1093\/cid\/ciad363","article-title":"Global Differences in the Management of Staphylococcus aureus Bacteremia: No International Standard of Care","volume":"77","author":"Westgeest","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","first-page":"495","article-title":"Staphylococcus aureus bacteremia in patients with SARS-CoV-2 infection","volume":"160","author":"Bloise","year":"2023","journal-title":"Med. Clin. Engl. Ed."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"ofaa518","DOI":"10.1093\/ofid\/ofaa518","article-title":"Staphylococcus aureus Bacteremia in Patients Infected with COVID-19: A Case Series","volume":"7","author":"Dupper","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"B\u00f6ing, C.W., Frob\u00f6se, N.J., Schaumburg, F., and Kampmeier, S. (2023). Impact of the COVID-19 Pandemic on the Management of Staphylococcus aureus Bloodstream Infections in a Tertiary Care Hospital. Pathogens, 12.","DOI":"10.3390\/pathogens12040611"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jinf.2015.09.037","article-title":"Infectious disease consultation for Staphylococcus aureus bacteremia\u2014A systematic review and meta-analysis","volume":"72","author":"Vogel","year":"2015","journal-title":"J. Infect."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/3\/326\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:54Z","timestamp":1760029014000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/3\/326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,20]]},"references-count":21,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["antibiotics14030326"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14030326","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,20]]}}}