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Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study - 26/11/20

Doi : 10.1016/S1473-3099(20)30447-3 
Richard Kuehl, MD a, b, Laura Morata, PhD a, Christian Boeing c, Isaac Subirana, PhD d, Harald Seifert, ProfMD e, f, Siegbert Rieg, ProfMD g, Winfried V Kern, ProfMD g, Hong Bin Kim, ProfMD h, Eu Suk Kim, MD h, Chun-Hsing Liao, MD i, Robert Tilley, MBChB j, Luis Eduardo Lopez-Cortés, PhD k, Martin J Llewelyn, ProfPhD l, Vance G Fowler, ProfMD m, Guy Thwaites, ProfPhD n, José Miguel Cisneros, ProfPhD o, Matt Scarborough, PhD p, Emmanuel Nsutebu, MD q, Mercedes Gurgui Ferrer, PhD r, José L Pérez, PhD s, Gavin Barlow, MD t, Susan Hopkins, MD u, Hugo Guillermo Ternavasio-de la Vega, PhD v, M Estée Török, PhD w, Peter Wilson, ProfMD x, Achim J Kaasch, ProfMD c, Alex Soriano, ProfPhD a,
on behalf of the

International Staphylococcus aureus collaboration study group and the ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis

  Members of the study group are listed in the acknowledgments
Richard Kuehl, Laura Morata, Christian Boeing, Isaac Subirana, Harald Seifert, Siegbert Rieg, Winfried V. Kern, Hong Bin Kim, Eu Suk Kim, Chun-Hsing Liao, Robert Tilley, Luis Eduardo Lopez-Cortés, Martin J. Llewelyn, Vance G. Fowler, Guy Thwaites, José Miguel Cisneros, Matt Scarborough, Emmanuel Nsutebu, Mercedes Gurgui Ferrer, José L. Pérez, Gavin Barlow, Susan Hopkins, Hugo Guillermo Ternavasio-de la Vega, Estée Török, Peter Wilson, Achim J. Kaasch, Alex Soriano, Christian Bernasch, Norma Jung, Karuna Lamarca Soria, Maria Alba Rivera Martínez, Nuria Prim, José Antonio Martínez, Miguel Marcos, Jesús Rodríguez Baño, Marina De Cueto, Kyoung-Ho Sung, Chung-Jong Kim, Chang Kyung Kang, Jung In Park, Stephen Morris-Jones, Musa Kamfose, Bernadette Young, Hannah Gott, Theodore Gouliouris, Luke Bedford, James Price

a Service of Infectious Diseases, Hospital Clínic of Barcelona, Barcelona, Spain 
b Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland 
c Institute of Medical Microbiology and Hospital Hygiene, Faculty of Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany 
d CIBER en Epidemiología y Salud Pública, Barcelona, Spain 
e Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine, University of Cologne, Cologne, Germany 
f German Center for Infection Research, Partner site Bonn-Cologne, Cologne, Germany 
g Division of Infectious Diseases, Department of Medicine II, Medical Center–University of Freiburg, Freiburg, Germany 
h Division of Infectious Diseases, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, South Korea 
i Infectious Diseases, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei City, Taiwan 
j Department of Microbiology, University Hospitals Plymouth NHS Trust, Plymouth, UK 
k Infectious Diseases and Clinical Microbiology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain 
l Department of Infectious Diseases and Microbiology, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK 
m Division of Infectious Diseases and International Health, Department of Medicine, Duke University School of Medicine, Durham, NC, USA 
n Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK 
o 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 
p Nuffield Department of Medicine, Oxford University Hospitals NHS Foundation, Oxford, UK 
q Tropical and Infectious Disease Unit, Royal Liverpool University Hospital, Liverpool, UK 
r Infectious Diseases Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain 
s Servicio de Microbiología and Unidad de Investigación, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria Illes Balears, Palma de Mallorca, Spain 
t Department of Infection, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK 
u Infectious Diseases Unit, Royal Free London NHS Foundation Trust, London, UK 
v Department of Internal Medicine, University Hospital of Salamanca-IBSAL, Salamanca, Spain 
w Department of Medicine, University of Cambridge, Cambridge, UK 
x Department of Microbiology and Virology, University College London Hospital NHS Foundation Trust, London, UK 

* Correspondence to: Prof Alex Soriano, Service of Infectious Diseases, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Spain Service of Infectious Diseases Hospital Clínic of Barcelona IDIBAPS University of Barcelona Barcelona 08036 Spain

Summary

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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