Comparative effectiveness of antibiotic therapy for carbapenem-resistant Enterobacterales (CRE) bloodstream infections in hospitalized US veterans

Carbapenem-resistant Enterobacterales bloodstream infections (CRE-BSI) increase mortality three-fold compared with carbapenem-susceptible bloodstream infections. Because these infections are rare, there is a paucity of information on mortality associated with different treatment regimens. This study examines treatment regimens and association with in-hospital, 30 day and 1 year mortality risk for patients with CRE-BSI. This retrospective cohort study identified hospitalized patients within the Veteran Affairs (VA) from 2013 to 2018 with a positive CRE blood culture and started antibiotic treatment within 5 days of culture. Primary outcomes were in-hospital, 30 day and 1 year all-cause mortality. Secondary outcomes were healthcare costs at 30 days and 1 year and infection 6 weeks post culture date. The propensity for receiving each treatment regimen was determined. Multivariable regression assessed the association between treatment and outcomes. There were 393 hospitalized patients from 2013 to 2018 included in the study. The cohort was male (97%) and elderly (mean age 71.0 years). Carbapenems were the most prescribed antibiotics (47%). In unadjusted analysis, ceftazidime/avibactam was associated with a lower likelihood of 30 day and 1 year mortality. After adjusting, ceftazidime/avibactam had a 30 day mortality OR of 0.42 (95% CI 0.17-1.02). No difference was found in incidence at 6 weeks post-infection or total costs at 30 days or 1 year post culture date by any treatments. In hospitalized veterans with CRE-BSI, none of the treatments were shown to be associated with all-cause mortality. Ceftazidime/avibactam trended towards protectiveness against 30 day and 1 year all-cause mortality. Use of ceftazidime/avibactam should be encouraged for treatment of CRE-BSI.