Weston, Gregory

Abstract Background The CDC reported a 35% increase in hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections during the COVID-19 pandemic. We evaluated patient outcomes following HO and community-onset (CO) CRE bloodstream infections (BSI). Methods Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between 30 April 2016 and 30 November 2019 with a CRE BSI were eligible. Infections were defined as CO or HO by CDC guidelines, and clinical characteristics and outcomes were compared. The primary outcome was desirability of outcome ranking (DOOR) 30 days after index culture. Difference in 30-day mortality was calculated with 95% CI. Results Among 891 patients with CRE BSI, 65% were HO (582/891). Compared to those with CO CRE, patients with HO CRE were younger [median 60 (Q1 42, Q3 70) years versus 65 (52, 74); P < 0.001], had fewer comorbidities [median Charlson comorbidity index 2 (1, 4) versus 3 (1, 5); P = 0.002] and were more acutely ill (Pitt bacteraemia score ≥4: 47% versus 32%; P < 0.001). The probability of a better DOOR outcome in a randomly selected patient with CO BSI compared to a patient with HO BSI was 60.6% (95% CI: 56.8%–64.3%). Mortality at 30-days was 12% higher in HO BSI (192/582; 33%) than CO BSI [66/309 (21%); P < 0.001]. Conclusion We found a disproportionately greater impact on patient outcomes with HO compared to CO CRE BSIs; thus, the recently reported increases in HO CRE infections by CDC requires rigorous surveillance and infection prevention methods to prevent added mortality.

Abstract Background Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). Objectives To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. Methods Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. Results The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients’ race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%–56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. Conclusions Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.