Factors associated with carriage of carbapenem-non-susceptible Enterobacteriaceae in North-Eastern France and outcomes of infected patients

Background: Carbapenems are frequently used as a last resort to treat infections caused by multidrug-resistant Gram-negative organisms, thus carbapenem-non-susceptible Enterobacteriaceae (CNSE) is an emerging health threat. Objectives: To assess risk factors and outcomes of CNSE carriage. Patients and methods: We conducted a matched case-control study in six hospitals in North-Eastern France. The controls were patients harbouring carbapenem-susceptible Enterobacteriaceae. Fifty-five cases and 110 controls were included. Results: Most of the CNSE isolates were Enterobacter cloacae and Klebsiella pneumoniae. Carbapenemase production was observed in 40% of isolates and they produced OXA-48 only. CNSE carriage was significantly associated with recent antibiotic use (P = 0.014), particularly carbapenems (P = 0.03) and fluoroquinolones (P = 0.016). A multivariate analysis using conditional logistic regression showed that the presence of concomitant infection(s) (OR: 9.83; 95% CI 3.04-21.39, P = 0.0031), nosocomial infections (OR: 7.84; 95% CI 2.00-12.54, P = 0.0063) and a high age (OR: 1.07; 95% CI 1.01-1.06, P = 0.038) were independently associated with CNSE carriage. Moreover, patients infected with CNSE had worse outcomes: fewer resolved infections at 1 month (P = 0.02), and they had a higher mortality rate (P = 0.0004) and longer hospital stays (P = 0.02). Conclusions: We identified three independent risk factors for CNSE carriage as well as worse outcomes in infected patients in North-Eastern France. This highlights the importance of early detection of CNSE and the need for antimicrobial therapy re-evaluation after bacteriological analysis has been performed.