A Cohort Study of the Impact of Carbapenem-Resistant Enterobacteriaceae Infections on Mortality of Patients Presenting with Sepsis

Abstract

The objective of this study is to evaluate the impact of carbapenem-resistant Enterobacteriaceae (CRE) infection on sepsis 30-day mortality. A retrospective cohort of patients >18 years old with sepsis and organ dysfunction or septic shock was conducted. Univariate analysis was done for variables potentially related to 30-day mortality, and the ones with P values of <0.05 were included in a backward stepwise hierarchic Cox regression model. Variables that remained with P values of <0.05 were retained in the model. A total of 1,190 sepsis episodes were analyzed. Gram-negative bacterial infections occurred in 391 (68.5%) of 571 patients with positive cultures, of which 69 (17.7%) were caused by a CRE organism. Patients with CRE infections had significantly higher 30-day mortality: 63.8% versus 33.4% (P < 0.01). CRE infection was also associated with a lower rate of appropriate empirical therapy (P < 0.01) and with the presence of septic shock (P < 0.01). In the hierarchic multivariate model, CRE remained significant when controlling for demographic variables, comorbidities, and infection site but lost significance when controlling for septic shock and appropriate empirical therapy. Older age (P < 0.01), HIV-positive status (P < 0.01), cirrhosis (P < 0.01), septic shock (P < 0.01), higher quick sepsis-related organ failure assessment (quick-SOFA) (P < 0.01), and appropriate empirical therapy (P = 0.01) remained in the final model. CRE infections were associated with higher crude mortality rates. A lower rate of appropriate empirical therapy and late diagnosis were more frequent in this group, and improvement of stewardship programs is needed. IMPORTANCE The importance of this work relies on exploring the impact of multidrug-resistant bacterial infections such as those with carbapenem-resistant Enterobacteriaceae (CRE) on sepsis mortality. These infections are growing at alarming rates worldwide and are now among the most frequent and difficult-to-treat bacteria due to the very few options for susceptible antimicrobials available. This study examined 1,190 sepsis episodes, and the main findings were as follows: (i) the prevalence of CRE infections significantly increased over time, (ii) CRE infection was associated with higher 30-day mortality than that of patients with other infections (63.8% versus 33.4%), and (iii) the effect of CRE on mortality was probably influenced by the fact that those patients received lower rates of empirical therapy with active antibiotics and were also diagnosed in more advanced stages of sepsis (septic shock). Those findings point to the need for rapid diagnostic methods to identify these bacteria and the need to adjust therapeutic guidelines to this worrisome epidemiological scenario.

Construction of a risk prediction model for subsequent bloodstream infection in intestinal carriers of carbapenem-resistant Enterobacteriaceae: a retrospective study in hematology department and intensive care unit

“…The course of CRE bloodstream infection (BSI) in immunocompromised patients is usually abrupt and fatal [4]. A cohort study of the impact of CRE infections on mortality of patients presenting with sepsis showed that patients with CRE infections had signi cantly higher 30-day mortality: 63.8% versus 33.4% (P < 0.01) [5].…”

Detection of carbapenemase-resistant Enterobacterales in blood culture in 15 minutes

“…Infection with CRE increases the risk for prolonged hospitalization, with risk of mortality being higher in patients with CRE bacteremia, and correlating directly with the development of septic shock and the use of incorrect empirical antibiotic therapy (6). Moreover, mortality risk associated with CP-CRE infections is 3-6 times higher compared to that of infections caused by a non-resistant bacteria (12).…”

“…Furthermore, antibiotic susceptibility testing (AST), which can only be performed after the growth of the pathogen colonies on solid medium, demands approximately 24 hours. Each delay in pathogen identification and antibiotic treatment adjustment has serious implications for patients, particularly with regards to infections with multidrug resistant bacteria such as carbapenem-resistant Enterobacterales (CRE) (4)(5)(6). Therefore, rapid assays for pathogen identification in BSI are needed.…”

Detection of Carbapenem-Resistant Enterobacterales in Simulated Blood Culture in 15 Minutes

“…Recently, the assay was demonstrated to perform well for direct detection of CRE bacteria in blood culture, without the need for bacterial cultivation [ 10 ]. Several studies have evaluated the reliability of the NG-Test CARBA 5 kit as a diagnostic tool for recognition of CRE in bacterial colonies [ 10 , 11 ]. The current work assessed the kit’s performance and lower limit of detection in blood CRE samples.…”