Richard Kuehl1, Laura Morata2, Christian Boeing3, Isaac Subirana4, Harald Seifert5, Siegbert Rieg6, Winfried V Kern6, Hong Bin Kim7, Eu Suk Kim7, Chun-Hsing Liao8, Robert Tilley9, Luis Eduardo Lopez-Cortés10, Martin J Llewelyn11, Vance G Fowler12, Guy Thwaites13, José Miguel Cisneros14, Matt Scarborough15, Emmanuel Nsutebu16, Mercedes Gurgui Ferrer17, José L Pérez18, Gavin Barlow19, Susan Hopkins20, Hugo Guillermo Ternavasio-de la Vega21, M Estée Török22, Peter Wilson23, Achim J Kaasch3, Alex Soriano24. 1. Service of Infectious Diseases, Hospital Clínic of Barcelona, Barcelona, Spain; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. 2. Service of Infectious Diseases, Hospital Clínic of Barcelona, Barcelona, Spain. 3. Institute of Medical Microbiology and Hospital Hygiene, Faculty of Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. 4. CIBER en Epidemiología y Salud Pública, Barcelona, Spain. 5. Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine, University of Cologne, Cologne, Germany; German Center for Infection Research, Partner site Bonn-Cologne, Cologne, Germany. 6. Division of Infectious Diseases, Department of Medicine II, Medical Center-University of Freiburg, Freiburg, Germany. 7. Division of Infectious Diseases, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea. 8. Infectious Diseases, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei City, Taiwan. 9. Department of Microbiology, University Hospitals Plymouth NHS Trust, Plymouth, UK. 10. Infectious Diseases and Clinical Microbiology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain. 11. Department of Infectious Diseases and Microbiology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK. 12. Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. 13. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 14. Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Instituto de Biomedicina de Sevilla, Seville, Spain. 15. Nuffield Department of Medicine, Oxford University Hospitals NHS Foundation, Oxford, UK. 16. Tropical and Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool, UK. 17. Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 18. Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears, Palma de Mallorca, Spain. 19. Department of Infection, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK. 20. Infectious Diseases Unit, Royal Free London NHS Foundation Trust, London, UK. 21. Department of Internal Medicine, University Hospital of Salamanca-IBSAL, Salamanca, Spain. 22. Department of Medicine, University of Cambridge, Cambridge, UK. 23. Department of Microbiology and Virology, University College London Hospital NHS Foundation Trust, London, UK. 24. Service of Infectious Diseases, Hospital Clínic of Barcelona, Barcelona, Spain. Electronic address: asoriano@clinic.cat.
Abstract
BACKGROUND: Staphylococcus aureus persistent bacteraemia is only vaguely defined and the effect of different durations of bacteraemia on mortality is not well established. Our primary aim was to analyse mortality according to duration of bacteraemia and to derive a clinically relevant definition for persistent bacteraemia. METHODS: We did a secondary analysis of a prospective observational cohort study at 17 European centres (nine in the UK, six in Spain, and two in Germany), with recruitment between Jan 1, 2013, and April 30, 2015. Adult patients who were consecutively hospitalised with monomicrobial S aureus bacteraemia were included. Patients were excluded if no follow-up blood culture was taken, if the first follow-up blood-culture was after 7 days, or if active antibiotic therapy was started more than 3 days after first blood culture. The primary outcome was 90-day mortality. Univariable and time-dependent multivariable Cox regression analysis were used to assess predictors of mortality. Duration of bacteraemia was defined as bacteraemic days under active antibiotic therapy counting the first day as day 1. FINDINGS: Of 1588 individuals assessed for eligibility, 987 were included (median age 65 years [IQR 51-75]; 625 [63%] male). Death within 90 days occurred in 273 (28%) patients. Patients with more than 1 day of bacteraemia (315 [32%]) had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture. Crude 90-day mortality increased from 22% (148 of 672) with 1 day of bacteraemia, to 39% (85 of 218) with 2-4 days, 43% (30 of 69) with 5-7 days, and 36% (10 of 28) with more than 7 days of bacteraemia. Metastatic infections developed in 39 (6%) of 672 patients with 1 day of bacteraemia versus 40 (13%) of 315 patients if bacteraemia lasted for at least 2 days. The second day of bacteraemia had the highest HR and earliest cutoff significantly associated with mortality (adjusted hazard ratio 1·93, 95% CI 1·51-2·46; p<0·0001). INTERPRETATION: We suggest redefining the cutoff duration for persistent bacteraemia as 2 days or more despite active antibiotic therapy. Our results favour follow-up blood cultures after 24 h for early identification of all patients with increased risk of death and metastatic infection. FUNDING: None.
BACKGROUND:Staphylococcus aureus persistent bacteraemia is only vaguely defined and the effect of different durations of bacteraemia on mortality is not well established. Our primary aim was to analyse mortality according to duration of bacteraemia and to derive a clinically relevant definition for persistent bacteraemia. METHODS: We did a secondary analysis of a prospective observational cohort study at 17 European centres (nine in the UK, six in Spain, and two in Germany), with recruitment between Jan 1, 2013, and April 30, 2015. Adult patients who were consecutively hospitalised with monomicrobial S aureus bacteraemia were included. Patients were excluded if no follow-up blood culture was taken, if the first follow-up blood-culture was after 7 days, or if active antibiotic therapy was started more than 3 days after first blood culture. The primary outcome was 90-day mortality. Univariable and time-dependent multivariable Cox regression analysis were used to assess predictors of mortality. Duration of bacteraemia was defined as bacteraemic days under active antibiotic therapy counting the first day as day 1. FINDINGS: Of 1588 individuals assessed for eligibility, 987 were included (median age 65 years [IQR 51-75]; 625 [63%] male). Death within 90 days occurred in 273 (28%) patients. Patients with more than 1 day of bacteraemia (315 [32%]) had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture. Crude 90-day mortality increased from 22% (148 of 672) with 1 day of bacteraemia, to 39% (85 of 218) with 2-4 days, 43% (30 of 69) with 5-7 days, and 36% (10 of 28) with more than 7 days of bacteraemia. Metastatic infections developed in 39 (6%) of 672 patients with 1 day of bacteraemia versus 40 (13%) of 315 patients if bacteraemia lasted for at least 2 days. The second day of bacteraemia had the highest HR and earliest cutoff significantly associated with mortality (adjusted hazard ratio 1·93, 95% CI 1·51-2·46; p<0·0001). INTERPRETATION: We suggest redefining the cutoff duration for persistent bacteraemia as 2 days or more despite active antibiotic therapy. Our results favour follow-up blood cultures after 24 h for early identification of all patients with increased risk of death and metastatic infection. FUNDING: None.
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