BACKGROUND: An outbreak of Clostridium difficile ribotype 027 infection (CDI) 
occurred at an university hospital, involving 19 departments. To determine what 
hospital-associated factors drove the outbreak of this particular strain we 
performed a case-control study.
METHODS: Cases (n = 79), diagnosed with CDI due to C. difficile ribotype 027 
were matched for age and treating medical specialty to four control patients (n 
= 316). Patients diagnosed with CDI due to other ribotypes were included as a 
second control group. A random selection of C. difficile ribotype 027 strains (n 
= 10) was genotyped by Whole Genome Sequencing (WGS).
FINDINGS: WGS showed the outbreak was likely caused by a single strain of C. 
difficile (two or less single-nucleotide variants between isolates). Ninety-five 
percent of cases had used antibiotics, compared to 56% of controls. Previous 
admission to the intensive care unit (ICU) (OR: 2.4, 95% CI 1.0-5.6), longer 
length of stay (LOS), and recent hospital admission were associated with CDI 
ribotype 027. Cases were less likely to have been admitted to a ward with a 
known isolated CDI patient (OR: 0.2, 95% CI 0.1-0.6). Analysis of patients who 
stayed at the ICU (35 cases; 51 controls), indicated that the use of selective 
decontamination of the digestive tract (SDD) and a longer LOS in the ICU were 
associated with CDI risk.
INTERPRETATION: In this large outbreak, any antibiotic use, including SDD use, 
appeared as a prerequisite for acquisition of the outbreak strain. The role of 
use of SDD and prolonged stay on the ICU could not be disentangled, but both 
factors can play a biologically plausible role in C. difficile acquisition and 
infection.