{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:45:09Z","timestamp":1792586709406,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"12","funder":[{"DOI":"10.13039\/100000133","name":"Agency for Healthcare Research and Quality","doi-asserted-by":"publisher","award":["K08HS025008"],"award-info":[{"award-number":["K08HS025008"]}],"id":[{"id":"10.13039\/100000133","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Resistance to all first-line antibiotics necessitates the use of less effective or more toxic \u201creserve\u201d agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for \u22651 active first-line antibiotic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate\/resistant in vitro to all \u00df-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to \u22651 first-line agent, and graded loss of active categories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Between 2009\u20132013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin\/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0\u20131.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1\u20131.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0\u20131.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3\u20135 to 1\u20132 to 0.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciy378","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T23:11:17Z","timestamp":1525734677000},"page":"1803-1814","source":"Crossref","is-referenced-by-count":421,"title":["Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents"],"prefix":"10.1093","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4420-9004","authenticated-orcid":false,"given":"Sameer S","family":"Kadri","sequence":"first","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland"},{"name":"Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Adjemian","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda"},{"name":"United States Public Health Service, Commissioned Corps, Rockville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Ling","family":"Lai","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicen B","family":"Spaulding","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Ricotta","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Rebecca","family":"Prevots","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara N","family":"Palmore","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanu","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital"},{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Klompas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital"},{"name":"Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P","family":"Dekker","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"John H","family":"Powers","sequence":"additional","affiliation":[{"name":"Clinical Research Directorate\/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony F","family":"Suffredini","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Hooper","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Fridkin","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality and Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L","family":"Danner","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"National Institutes of Health Antimicrobial Resistance Outcomes Research Initiative (NIH\u2013ARORI)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,23]]},"reference":[{"key":"2024111411404963700_CIT0001","volume-title":"Antibiotic resistance threats in the United States, 2013","author":"Centers for Disease Control and Prevention"},{"key":"2024111411404963700_CIT0002","article-title":"Antimicrobial resistance: tackling a crisis for the health and wealth of nations","volume-title":"Review on antimicrobial resistance. 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