Gram-negative bacteraemia; A multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals

on behalf of the United Kingdom Clinical Infection Research Group

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55 Citations (Scopus)


Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (<0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors.

Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalClinical Microbiology and Infection
Issue number3
Early online date11 Nov 2015
Publication statusPublished - 01 Mar 2016
Externally publishedYes

Bibliographical note

Funding Information:
The work was conducted as part of the authors' routine clinical work. ASW is supported by the NIHR Oxford Biomedical Research Centre.

Funding Information:
Full list of study sites and contributors: Barts Health NHS Trust; Mark Melzer and Frederick Pink; Brighton and Sussex University Hospitals NHS Trust; Jennifer Fitzpatrick, Gill Jones, Martin Llewelyn and Joanna Peters; Guys and St Thomas'' Hospitals NHS Foundation Trust, London; Jason Biswas, Jonathan Edgeworth, Lucy Guile and Antonio Querol-Rubiera; Heart of England Foundation NHS Trust, Birmingham; Abid Hussain, Neil Jenkins, Ed Moran and Devedas Pillay; NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford; Matthew Scarborough and Tom Rawlinson; Plymouth Hospitals NHS Trust, Plymouth; Ryan Judge and Robert Tilley; Surrey and Sussex Healthcare NHS Trust, Redhill; Jasmin Islam; UCLH NHS Foundation Trust, London; Anita Lavery and Stephen Morris-Jones; Western Sussex Hospitals NHS Foundation Trust, Chichester; James Price; Royal Liverpool University Hospital, Liverpool; Joseph Lewis; Emmanuel Nsutebu; Victoria Parris; Reela Varghese.

Publisher Copyright:
© 2015 European Society of Clinical Microbiology and Infectious Diseases.


  • Adult
  • Antibiotic therapy
  • Bloodstream infection
  • Gram-negative bacteria
  • Mortality

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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