The changing epidemiology and long-term outcomes of patients with CRE infections

Background: The impact of organism species and underlying comorbidities on long-term clinical outcomes for patients with carbapenem-resistant Enterobacterales (CRE) infections is unknown. Methods: Patients with CRE-positive cultures from 2011 to 2019 were monitored for 1-year. Patients without signs of infection were categorized as colonization. Recurrent cases were defined as isolation of the same CRE species >90 days after the index case. Results: 720 patients met inclusion criteria and accounted for 749 index cases, which decreased over time. The median (range) age was 61 (20–97) years, 53% (397/749) were male, 20% (151/749) received solid organ transplant (SOT), and 44% resided in the ICU at the time of CRE isolation. The colonization rate was 34% (257/749). Pneumonia and bacteremia represented the most common infection types accounting for 25% (185/749) and 13% (95/749) of all cases, respectively. Klebsiella pneumoniae was most common pathogen (58%), followed by Enterobacter cloacae complex (23%), and Escherichia coli (10%). Of the 554 sequenced isolates, 35% (195/554) were KPC-2, 32% (175/554) KPC-3, and 32% (177/554) non-KPC-producing. This changed over time where KPC-2-producing CRE were most prevalent in 2011, KPC-3 most prevalent between 2015–2017, and non-KPC from 2018–2019. Among 90-day survivors, the CRE recurrence rate was 21% (108/513). Charlson comorbidity index (OR: 1.11; 95% CI: 1.05–1.18; P < .001), isolation of a prior CR pathogen (OR: 2.49; 95% CI 1.32–4.72; P = .005), and ICU admission (OR: 3.35; 95% CI 2.14–5.24; P < .001) were independently associated with 90-day mortality, while SOT was associated with lower 90-day mortality (OR: 0.55; 95% CI 0.32–0.94; P = .029). Overall, 90-day mortality rates were lower among patients with CRE-positive cultures between years 2016 – 2019 (24% [63/262]) compared to years 2011 – 2015 (35.5% [173/487]; P = .001). Conclusion: CRE are increasingly diverse and associated with significant morbidity and healthcare utilization across varying patient groups. Long-term survival of patients infected with CRE has improved over time while overall incidence of CRE has decreased.