Risk and prognosis of infection and colonisation by carbapenemase-producing Citrobacter freundii in the North Denmark Region during 2012–2023: a matched case–control and cohort study

Since October 2012, NDM-1-producing Citrobacter freundii has caused a prolonged outbreak at Aalborg University Hospital, Denmark. Despite infection control efforts, transmission persisted in haematology and abdominal surgery wards. This study aimed to identify risk factors for infection or colonisation with ST18 NDM-1-producing C. freundii and to assess all-cause mortality. We conducted a matched case–control and cohort study (2012–2023). Cases were patients with ST18 NDM-1-producing C. freundii detected in clinical or screening specimens. For each case, eight controls without C. freundii were selected from the same ward using risk-set sampling and matched on specimen date. Conditional logistic regression was used to identify risk factors, and Cox regression to estimate hazard ratios (HRs) for all-cause mortality. Sixty-nine cases and 552 controls were included. Strongest risk factors were prolonged hospital stay (>14 vs. ≤7 days; OR=6.4, 95% CI 3.6-11.3), peritoneal disease (OR=4.4, 95% CI 1.5–13.3), pancreatobiliary disorders (OR=5.5, 95% CI 3.0–10.3), biliary tract surgery (OR=4.6, 95% CI 2.7–7.8), pancreatic surgery (OR=4.4, 95% CI 2.2–8.6), and in-hospital exposure to vancomycin (OR=13.9, 95% CI 6.8–28.4), beta-lactam/beta-lactamase inhibitors (OR=8.8, 95% CI 4.2–18.2), fluoroquinolones (OR=8.2, 95% CI 4.6–14.9) or systemic antifungals (OR=8.6, 95% CI 4.7–15.6). Thirty-day mortality was higher among cases (adjusted HR=2.2, 95% CI 1.1–4.3), while 90- and 365-day mortality did not differ. Infection or colonisation with ST18 NDM-1-producing C. freundii was associated with abdominal infections, invasive surgical procedures, broad-spectrum antimicrobial exposure, and higher short-term mortality, likely reflecting underlying disease severity.