Clinical outcomes and treatment effectiveness in patients with carbapenem-resistant Enterobacterales infections: a multicenter retrospective cohort study.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) infections carry high mortality and limited treatment options. We evaluated outcomes among adults with CRE infections at Ministry of National Guard-Health Affairs facilities in Saudi Arabia, comparing monotherapy with combination therapy. METHODS: This multicenter retrospective cohort study included adults (≥18 years) with CRE infections during 2020-2024 at King Abdulaziz Medical City (Jeddah and Riyadh). CRE was defined phenotypically per CLSI criteria (first isolate per patient). Bivariate analyses, multivariate logistic regression, and Kaplan-Meier survival analysis compared monotherapy and combination therapy. RESULTS: Among 224 patients (median age 70 years; 62.5% male), overall mortality was 43.3%, and Klebsiella pneumoniae accounted for 96.0% of isolates. Combination therapy was associated with higher mortality than monotherapy (44.5% vs. 26.7%; P = .047) and remained independently associated with mortality after adjustment for age, gender, and comorbidities (adjusted OR = 2.28, 95% CI: 1.08-4.83; P = .032). A significant treatment-mortality difference was seen in patients without solid tumors (P = .031) but not in those with solid tumors (P = 1.000). Respiratory and blood infections carried the highest mortality (58.3% and 55.3%). CONCLUSIONS: CRE infections carry a high mortality burden among adults in Saudi Arabia. The higher mortality with combination therapy may, in part, reflect confounding by indication, with broader-spectrum regimens prescribed for sicker patients whose severity was not captured. Prospective studies with disease-severity scoring and individualized treatment are needed, particularly for immunocompromised patients.