Influence of antibiotics and case exposure on hospital-acquired Clostridium difficile infection independent of illness severity.
BACKGROUND
Previous studies of the association between antibiotic exposure and risk of hospital-acquired Clostridium difficile-associated infection (CDI) have not fully accounted for patient severity of illness, and competing risks.


OBJECTIVE
To determine the potential effects of interventions on hospital-acquired CDI risk.


METHODS
All adults admitted to a teaching hospital between 2004 and 2014 for more than two days were included. Exposures to all antibiotics and cases of CDI were determined. Patients were followed until discharge from hospital, death, or acquisition of hospital-acquired CDI (defined as positive toxin assay in unformed stool >2 days following admission). Multivariable proportional hazards competing-risks modelling with time-dependent covariates was used, accounting for patient severity of illness using the Escobar model.


RESULTS
In all, 208,104 patients were studied. Hospital-acquired CDI risk was 0.46 events per 1000 patient-days, decreasing significantly during the study period. Compared to the 5thpercentile hospital death risk (0.02%), patients with a 50% risk of death in hospital had an adjusted hazard ratio (aHR) of hospital-acquired CDI of 5.5. Exposure to some antibiotics significantly increased hospital-acquired CDI risk, being highest for carbapenems (aHR: 1.47 after one week of continuous exposure) and intravenous vancomycin (aHR: 1.53). On the ward, sharing a room with other patients newly diagnosed with CDI significantly increased the risk of subsequent disease (aHR: 1.16 on CDI diagnosis day).


CONCLUSIONS
The primary determinant of hospital-acquired CDI was patient severity of illness. Exposure to both antibiotics and other patients with CDI significantly increased the subsequent risk of hospital-acquired CDI but this risk was small relative to patient severity of illness.
Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
A J
AJ
Forster
Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Toronto Hospital, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
N
N
Daneman
Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. Electronic address: carlv@ohri.ca.
C
C
van Walraven
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016360:Clostridioides difficile / Q000302:isolation & purification*; D003015:Clostridium Infections / Q000139:chemically induced / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D003092:Colitis / Q000139:chemically induced / Q000453:epidemiology* / Q000382:microbiology; D003428:Cross Infection / Q000139:chemically induced / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D004363:Drug Utilization; D004781:Environmental Exposure; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult
D000900:Anti-Bacterial Agents
Antibiotics; Clostridium difficile infection; Competing risks; Hospital-acquired infection; Proportional hazards modelling; Time-dependent covariates