title: Incidence of infective endocarditis in England, 2000-13: a secular trend, interrupted time-series analysis.
abstract: BACKGROUND
  Antibiotic prophylaxis given before invasive dental procedures in patients at risk of developing infective endocarditis has historically been the focus of infective endocarditis prevention. Recent changes in antibiotic prophylaxis guidelines in the USA and Europe have substantially reduced the number of patients for whom antibiotic prophylaxis is recommended. In the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) recommended complete cessation of antibiotic prophylaxis for prevention of infective endocarditis in March, 2008. We aimed to investigate changes in the prescribing of antibiotic prophylaxis and the incidence of infective endocarditis since the introduction of these guidelines.
  
  
  METHODS
  We did a retrospective secular trend study, analysed as an interrupted time series, to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of infective endocarditis in England. We analysed data for the prescription of antibiotic prophylaxis from Jan 1, 2004, to March 31, 2013, and hospital discharge episode statistics for patients with a primary diagnosis of infective endocarditis from Jan 1, 2000, to March 31, 2013. We compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using segmented regression analysis of the interrupted time series.
  
  
  RESULTS
  Prescriptions of antibiotic prophylaxis for the prevention of infective endocarditis fell substantially after introduction of the NICE guidance (mean 10,900 prescriptions per month [Jan 1, 2004, to March 31, 2008] vs 2236 prescriptions per month [April 1, 2008, to March 31, 2013], p<0·0001). Starting in March, 2008, the number of cases of infective endocarditis increased significantly above the projected historical trend, by 0·11 cases per 10 million people per month (95% CI 0·05-0·16, p<0·0001). By March, 2013, 35 more cases per month were reported than would have been expected had the previous trend continued. This increase in the incidence of infective endocarditis was significant for both individuals at high risk of infective endocarditis and those at lower risk.
  
  
  CONCLUSIONS
  Although our data do not establish a causal association, prescriptions of antibiotic prophylaxis have fallen substantially and the incidence of infective endocarditis has increased significantly in England since introduction of the 2008 NICE guidelines.
  
  
  BACKGROUND
  Heart Research UK, Simplyhealth, and US National Institutes of Health.
authors.affiliation: Department of Cardiology, Taunton and Somerset NHS Trust, Taunton, Somerset, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dayer
authors.affiliation: Integrated Care Research, University of Surrey, Guildford, Surrey, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Jones
authors.affiliation: Cardiothoracic Services, Department of Cardiology, John Radcliffe Hospital, Oxford, UK.
authors.forename: Bernard
authors.initials: B
authors.lastname: Prendergast
authors.affiliation: Division of Infectious Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Larry M
authors.initials: LM
authors.lastname: Baddour
authors.affiliation: Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Lockhart
authors.affiliation: Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA; Unit of Oral & Maxillofacial Surgery & Medicine, University of Sheffield School of Clinical Dentistry, Sheffield, UK. Electronic address: m.thornhill@sheffield.ac.uk.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Thornhill
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D019072:Antibiotic Prophylaxis / Q000706:statistics & numerical data / Q000639:trends; D002981:Clindamycin / Q000008:administration & dosage; D003729:Dental Care / Q000009:adverse effects; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004696:Endocarditis / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D004739:England / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D065186:Interrupted Time Series Analysis; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin; D000658:Amoxicillin