title: Excess length of stay and mortality due to Clostridium difficile infection: a multi-state modelling approach.
abstract: BACKGROUND
  The burden of healthcare-associated infections, such as healthcare-acquired Clostridium difficile (HA-CDI), can be expressed in terms of additional length of stay (LOS) and mortality. However, previous estimates have varied widely. Although some have considered time of infection onset (time-dependent bias), none considered the impact of severity of HA-CDI; this was the primary aim of this study.
  
  
  METHODS
  The daily risk of in-hospital death or discharge was modelled using a Cox proportional hazards model, fitted to data on patients discharged in 2012 from a large English teaching hospital. We treated HA-CDI status as a time-dependent variable and adjusted for confounders. In addition, a multi-state model was developed to provide a clinically intuitive metric of delayed discharge associated with non-severe and severe HA-CDI respectively.
  
  
  RESULTS
  Data comprised 157 (including 48 severe) HA-CDI cases among 42,618 patients. HA-CDI reduced the daily discharge rate by nearly one-quarter [hazard ratio (HR): 0.72; 95% confidence interval (CI): 0.61-0.84] and increased the in-hospital death rate by 75% compared with non-HA-CDI patients (HR: 1.75; 95% CI: 1.16-2.62). Whereas overall HA-CDI resulted in a mean excess LOS of about seven days (95% CI: 3.5-10.9), severe cases had an average excess LOS which was twice (∼11.6 days; 95% CI: 3.6-19.6) that of the non-severe cases (about five days; 95% CI: 1.1-9.5).
  
  
  CONCLUSIONS
  HA-CDI contributes to patients' expected LOS and risk of mortality. However, when quantifying the health and economic burden of hospital-onset of HA-CDI, the heterogeneity in the impact of HA-CDI should be accounted for.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK; Public Health England, Colindale, London, UK. Electronic address: esther.vankleef@lshtm.ac.uk.
authors.forename: E
authors.initials: E
authors.lastname: van Kleef
authors.affiliation: Public Health England, Colindale, London, UK; Imperial College London, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Green
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust and King's College, London, UK.
authors.forename: S D
authors.initials: SD
authors.lastname: Goldenberg
authors.affiliation: Public Health England, Colindale, London, UK.
authors.forename: J V
authors.initials: JV
authors.lastname: Robotham
authors.affiliation: University College London, London, UK.
authors.forename: B
authors.initials: B
authors.lastname: Cookson
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK; Public Health England, Colindale, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Jit
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: W J
authors.initials: WJ
authors.lastname: Edmunds
authors.affiliation: Public Health England, Colindale, London, UK.
authors.forename: S R
authors.initials: SR
authors.lastname: Deeny
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016360:Clostridioides difficile; D003428:Cross Infection / Q000401:mortality*; D004761:Enterocolitis, Pseudomembranous / Q000401:mortality*; D017052:Hospital Mortality; D006801:Humans; D007902:Length of Stay; D008875:Middle Aged; D010351:Patient Discharge; D016016:Proportional Hazards Models
keywords: Clostridium difficile infection; Length of hospital stay; Mortality