title: Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.
abstract: 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 (p <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.
authors.affiliation: Department of Infectious Diseases and Microbiology, Royal Sussex County Hospital, Brighton, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Fitzpatrick
authors.affiliation: Centre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, Kings College London and Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK.
authors.forename: J S
authors.initials: JS
authors.lastname: Biswas
authors.affiliation: Centre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, Kings College London and Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Edgeworth
authors.affiliation: Department of Microbiology, Surrey and Sussex Healthcare NHS Trust, Redhill, UK.
authors.forename: J
authors.initials: J
authors.lastname: Islam
authors.affiliation: Department of Microbiology, Infection and Tropical Medicine, Heart of England NHS Trust, Birmingham, UK.
authors.forename: N
authors.initials: N
authors.lastname: Jenkins
authors.affiliation: Department of Microbiology, Plymouth Hospitals NHS Trust, Plymouth, UK.
authors.forename: R
authors.initials: R
authors.lastname: Judge
authors.affiliation: Department of Clinical Microbiology and Virology, UCLH NHS Foundation Trust, London, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lavery
authors.affiliation: Department of Infection, Barts Health NHS Trust, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Melzer
authors.affiliation: Department of Clinical Microbiology and Virology, UCLH NHS Foundation Trust, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Morris-Jones
authors.affiliation: Tropical and Infectious Disease Unit Royal Liverpool University Hospital, Liverpool, UK.
authors.forename: E F
authors.initials: EF
authors.lastname: Nsutebu
authors.affiliation: Department of Infectious Diseases and Microbiology, Royal Sussex County Hospital, Brighton, UK.
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.affiliation: Department of Microbiology, Infection and Tropical Medicine, Heart of England NHS Trust, Birmingham, UK.
authors.forename: D G
authors.initials: DG
authors.lastname: Pillay
authors.affiliation: Department of Infection, Barts Health NHS Trust, London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Pink
authors.affiliation: Department of Microbiology, Western Sussex Hospitals NHS Foundation Trust, Chichester, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Price
authors.affiliation: NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Scarborough
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: G E
authors.initials: GE
authors.lastname: Thwaites
authors.affiliation: Department of Microbiology, Plymouth Hospitals NHS Trust, Plymouth, UK.
authors.forename: R
authors.initials: R
authors.lastname: Tilley
authors.affiliation: NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Walker
authors.affiliation: Department of Infectious Diseases and Microbiology, Royal Sussex County Hospital, Brighton, UK; Division of Medicine, Brighton and Sussex Medical School, Falmer, UK. Electronic address: m.j.llewelyn@bsms.ac.uk.
authors.forename: M J
authors.initials: MJ
authors.lastname: Llewelyn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D002423:Cause of Death; D015897:Comorbidity; D004739:England / Q000453:epidemiology; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents
keywords: Adult; Gram-negative bacteria; antibiotic therapy; bloodstream infection; mortality