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

Background: 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. Objectives: 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. Methods: 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. Results: 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). Conclusion: 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.