Clinical epidemiology of carbapenem-resistant gram-negative sepsis among hospitalized patients: Shifting burden of disease?

Background: Infections caused by carbapenem-resistant gram-negative bacilli are an emerging public health threat. However, there is a paucity of data examining comparative incidence rates, risk factors, and outcomes in this population. Methods: This single-center retrospective cohort study was conducted at an urban tertiary-care academic medical center. We included patients admitted from 2012 to 2015 who met the following criteria: i) age ≥ 18 years; and ii) culture positive for carbapenem-resistant Enterobacteriaceae (CRE) or carbapenem-resistant non-Enterobacteriaceae (CRNE) from any site. Exclusion criteria were: i) < 2 systemic inflammatory response criteria; ii) cystic fibrosis; and iii) no targeted treatment. We evaluated hospital survival by Cox regression and year-by-year differences in the distribution of cases by the Cochran-Armitage test. Results: 448 patients were analyzed (CRE, n = 111 [24.8%]; CRNE, n = 337 [75.2%]). CRE sepsis cases increased significantly over the study period (P <.001), driven primarily by increasing incidence of Enterobacter spp. infection (P =.004). No difference was observed in hospital survival between patients with CRE versus CRNE sepsis (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.83-2.02; P =.285), even after adjusting for confounding factors (adjusted HR, 1.08; 95% CI, 0.62-1.87; P =.799). Conclusions: Clinical outcomes did not differ between patients with CRE versus CRNE sepsis. Dramatic increases in CRE, particularly Enterobacter spp., appear to be causing a shift in the burden of clinically significant carbapenem-resistant gram-negative infection.