title: The influence of statin exposure on inflammatory markers in patients with early bacterial infection: pilot prospective cohort study.
abstract: BACKGROUND
  In the context of infection, progressive illness resulting in acute organ dysfunction is thought to be secondary to inflammatory response. Our aims were to determine risk factors for progressive illness following infection in a low-risk hospitalised cohort, including the impact of prior stain therapy.
  
  
  METHODS
  We performed a prospective observational cohort study on two adult acute medical wards of a single tertiary academic hospital. We screened drug prescription charts of all adult acute medical admissions for inclusion criteria of inpatient administration of antibiotics for more than 24 hours for a microbiologically confirmed or clinically suspected infection. Patients were followed until admission to a high dependency unit (HDU) or intensive care unit (ICU), discharge from hospital, or to a maximum of 10 days. Outcomes were evolution of systemic inflammatory response syndrome (SIRS) criteria, white cell count and C-reactive protein measurements, and adverse clinical outcomes. We constructed multivariable models accounting for repeated within-patient measurements to determine associations between a priori selected predictors (days since admission, age, gender, Charlson score, prior statin exposure) and selected outcomes.
  
  
  RESULTS
  We enrolled 209 patients; 27.8% were statin users and the commonest infection was pneumonia (51.0%). Most (88.0%) had at least 1 SIRS criterion on admission, and 76 (37.3%) manifested additional SIRS criteria over time. Risks of admission to HDU/ICU (3.3%) and of 30-day mortality (5.7%) were low. The proportion of patients with at least 1 SIRS criterion, mean CRP, and mean WBC all decreased over time. Multivariable regression models identified days since hospital admission as the only variable associated with daily presence of SIRS criteria, WCC, or CRP (adjusted OR <1 and p < 0.0001 in all analyses). Statin exposure was not a significant predictor.
  
  
  CONCLUSIONS
  This cohort of ward patients treated for infection had a low risk of clinical deterioration, inflammatory markers improved over time, and statin exposure was not associated with any outcome. Future larger studies may identify risk factors for progression of illness in this population and plausible surrogate endpoints for evaluation in clinical trials.
authors.affiliation: Division of Asthma, Allergy and Lung Biology, King's College London, Department of Critical Care Medicine, St. Thomas' Hospital, 1st Floor, East Wing, Westminster Bridge Road, London, SE1 7EH UK.
authors.forename: Manu
authors.initials: M
authors.lastname: Shankar-Hari
authors.affiliation: Emergency Department, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD UK.
authors.forename: Antonia
authors.initials: A
authors.lastname: Donnelly
authors.affiliation: Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, M4N 3M5 Canada.
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Pinto
authors.affiliation: School of Pharmacy, University College London, London, UK ; Department of Pharmacy and Critical Care, Guys and St Thomas NHS Foundation Trust, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH UK.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Salih
authors.affiliation: Department of Pharmacy and Critical Care, Guys and St Thomas NHS Foundation Trust, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH UK ; Institute of Pharmaceutical Sciences, Kings College London, London, UK.
authors.forename: Cathrine
authors.initials: C
authors.lastname: McKenzie
authors.affiliation: Centre for Critical Illness Data Sciences Research, Division of Health & Social Care Research, King's College London, Department of Critical Care Medicine, 1st Floor, East Wing, St. Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH UK.
authors.forename: Marius
authors.initials: M
authors.lastname: Terblanche
authors.affiliation: Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute and University of Toronto, 2075 Bayview Avenue, Toronto, M4N 3M5 Canada.
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007249:Inflammation / Q000382:microbiology*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010865:Pilot Projects; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein
keywords: Biomarkers; Progression of illness; Sepsis; Surrogate end-points