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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

  • Andrew Stewardson (a1), Carolina Fankhauser (a1), Giulia De Augelis (a2), Peter Rohner (a3), Edith Safran (a3), Jacques Schrenzel (a4), Didier Pittet (a1) and Stephan Harbarth (a1)...

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.


Retrospective cohort study.


A 2,200-bed academic medical center in Geneva, Switzerland.


Patients admitted during 2009.


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.


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.


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.

Corresponding author
Service de Prévention et Contrôle de l'Infection, Hôpitaux Universitaires de Genève, Rue Gabrielle-Perret-Gentil 4, CH-1211 Genève 14, Switzerland (
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Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
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