Background: Bloodstream infections (BSI) caused by carbapenemase-producing Enterobacterales (CPE) represent a significant threat to patients with acute leukemia due to their high mortality. Ceftazidime–avibactam (CAZ-AVI) has emerged as a therapeutic alternative against these infections; however, its efficacy in immunocompromised patients remains unclear. Objective: To determine the impact of ceftazidime–avibactam on mortality due to BSI caused by CPE in patients with acute leukemia. Design: A retrospective cohort study was conducted at the Hospital Nacional Edgardo Rebagliati Martins in Lima, Peru. Methods: We included patients diagnosed with acute leukemia who developed BSI due to CPE during their hospital stays. Mortality was assessed for up to 30 days after BSI onset. Results: We evaluated 41 patients with a median age of 51 years; 56.1% had acute myeloid leukemia and 43.9% had acute lymphoblastic leukemia. Mortality at 30 days occurred in 60.9% of patients. The most frequent type of chemotherapy administered was induction (51.2%). Empiric antibiotic therapy with meropenem was administered to 97.6% of the patients, and ceftazidime–avibactam was prescribed as a targeted therapy to 48.8%. In the multivariate Cox regression model, the prescription of ceftazidime–avibactam reduced the risk of death (adjusted hazard ratio, 0.29; 95% CI: 0.09–0.92; p = 0.012) compared with those who received other antibiotic therapies, such as colistin. Conclusion: In patients with acute leukemia who developed bloodstream infections due to CPE during hospitalization, the prescription of ceftazidime–avibactam reduced 30-day mortality risk.