title: Burden of bloodstream infection caused by extended-spectrum β-lactamase-producing enterobacteriaceae determined using multistate modeling at a Swiss University Hospital and a nationwide predictive model.
abstract: OBJECTIVE
  To obtain an unbiased estimate of the excess hospital length of stay (LOS) and cost attributable to extended-spectrum β-lactamase (ESBL) positivity in bloodstream infections (BSIs) due to Enterobacteriaceae.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  A 2,200-bed academic medical center in Geneva, Switzerland.
  
  
  METHODS
  Patients admitted during 2009.
  
  
  METHODS
  We used multistate modeling and Cox proportional hazards models to determine the excess LOS and adjusted end-of-LOS hazard ratio (HR) for ESBL-positive and ESBL-negative BSI. We estimated economic burden as the product of excess LOS and average bed-day cost. Patient-level accounting data provided a complementary analysis of economic burden. A predictive model was fitted to national surveillance data.
  
  
  RESULTS
  Thirty ESBL-positive and 96 ESBL-negative BSI cases were included. The excess LOS attributable to ESBL-positive and ESBL-negative BSI was 9.4 (95% confidence interval [CI], 0.4-18.4) and 2.6 (95% CI, 0.7-5.9) days, respectively. ESBL positivity was therefore associated with 6.8 excess days and CHF 9,473 per BSI. The adjusted end-of-LOS HRs for ESBL-positive and ESBL-negative BSI were 0.62 (95% CI, 0.43-0.89) and 0.90 (95% CI, 0.74-1.10), respectively. After reimbursement, the average financial loss per acute care episode in ESBL-positive BSI, ESBL-negative BSI, and control cohorts was CHF 48,674, 48,131, and 13,532, respectively. Our predictive model estimated that the nationwide cost of third-generation cephalosporin resistance would increase from CHF 2,084,000 in 2010 to CHF 3,526,000 in 2015.
  
  
  CONCLUSIONS
  This is the first hospital-wide analysis of excess LOS attributable to ESBL positivity determined using multistate modeling to avoid time-dependent bias. These results may inform health-economic evaluations of interventions targeting ESBL control.
authors.affiliation: Infection Control Program, University of Geneva Hospitals and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stewardson
authors.forename: Carolina
authors.initials: C
authors.lastname: Fankhauser
authors.forename: Giulia
authors.initials: G
authors.lastname: De Angelis
authors.forename: Peter
authors.initials: P
authors.lastname: Rohner
authors.forename: Edith
authors.initials: E
authors.lastname: Safran
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.forename: Didier
authors.initials: D
authors.lastname: Pittet
authors.forename: Stephan
authors.initials: S
authors.lastname: Harbarth
mesh_terms: D000368:Aged; D016470:Bacteremia / Q000191:economics* / Q000382:microbiology; D016001:Confidence Intervals; D017281:Cost of Illness; D003428:Cross Infection / Q000191:economics* / Q000453:epidemiology / Q000382:microbiology; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000191:economics* / Q000453:epidemiology / Q000382:microbiology; D005260:Female; D005544:Forecasting; D006785:Hospitals, University; D006801:Humans; D007902:Length of Stay / Q000191:economics* / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D017678:Sex Distribution; D013557:Switzerland; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D001618:beta-Lactamases