Ceftazidime/avibactam alone or in combination with an aminoglycoside for treatment of carbapenem-resistant Enterobacterales infections: A retrospective cohort study

•Retrospective study of 303 CRE-infected patients treated with ceftazidime/avibactam.•Age, empiric aminoglycoside use, and ICU stay were associated with 30-day mortality.•Patients receiving an aminoglycoside were more likely to be in the ICU.•A subanalysis in only the patients who received an aminoglycoside was performed.•In subanalysis, adding aminoglycoside trended toward protectiveness of mortality. Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear. To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam. This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed. A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013–1.093), presence in the ICU (aOR 2.704, 95% CI 1.071–6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797–11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n = 77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089–1.155). In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill. [Display omitted]