Risk factors, impact on outcomes, and molecular epidemiology of infections caused by carbapenem-resistant Enterobacterales in intensive care patients: a multicenter matched case-control study in Brazil.

Abstract

Objective: To evaluate risk factors, molecular profiles, and hospital mortality of carbapenem-resistant Enterobacterales (CRE) infections in intensive care unit patients.

Methods: In this retrospective, multicenter cohort study, intensive care unit admissions from 52 intensive care units between January 2019 and December 2020 were analyzed in a nested case-control design. Patients with carbapenem-resistant Enterobacterales infections were propensity score-matched 1:1 to those with carbapenem-susceptible Enterobacterales infections. Hierarchical conditional logistic regression identified risk factors for carbapenem-resistant Enterobacterales, and multivariable logistic regression assessed the association of carbapenem-resistant Enterobacterales with 60-day in-hospital mortality. Molecular genotyping was also conducted.

Results: Matching resulted in 250 carbapenem-resistant Enterobacterales patients and 250 carbapenem-susceptible Enterobacterales patients. Sepsis was more common in the carbapenem-resistant Enterobacterales group (58% versus 35%; p < 0.001). Risk factors for carbapenem-resistant Enterobacterales included major premorbid assistance requirements (OR 1.72, 95%CI 0.99 - 3.01; p = 0.06) and intensive care unit readmission (OR 1.87, 95%CI 1.00 - 3.49; p = 0.05), although with weak associations. Acute COVID-19 (OR 3.55, 95%CI 1.96 - 6.45; p < 0.001) also increased the odds of resistance. Carbapenem-resistant Enterobacterales infection was associated with twice the likelihood of 60-day mortality after adjusting for covariates (OR 1.95, 95%CI 1.26 - 3.02; p < 0.001). The predominant bacteria and carbapenemase resistance genes included Klebsiella pneumoniae (79%), Klebsiella pneumoniae carbapenemase (73%), New Delhi metallo-beta-lactamase (13%), and xacillinase-48 (9%).

Conclusion: Carbapenem-resistant Enterobacterales-related infections in intensive care unit patients were associated with major premorbid dependence, intensive care unit readmission, and acute COVID-19. In addition, carbapenem-resistant Enterobacterales infections were independently associated with poorer hospital outcomes. This study also characterized the resistance profile of Enterobacterales in Brazilian intensive care units, which are dominated by K. pneumoniae with high rates of carbapenemase and increased rates of New Delhi metallo-beta-lactamase, in comparison with previous reports.