Cefiderocol-containing regimens for the treatment of carbapenem-resistant A. baumannii ventilator-associated pneumonia: a propensity-weighted cohort study

Background: Cefiderocol is a novel β-lactam with activity against carbapenem-resistant Acinetobacter baumannii (CRAB), but its role in CRAB pulmonary infections is controversial due to limited evidence. Objectives: To assess the association between cefiderocol-containing regimens treatment and 28-day mortality in carbapenem-resistant A. baumannii ventilator-associated pneumonia (VAP). Methods: An observational cohort study including critically ill COVID-19 patients with CRAB-VAP admitted to two ICUs of a large academic hospital in Rome between September 2020 and December 2022. The primary outcome was 28-day all-cause mortality. A propensity score was created to balance the cefiderocol- and non-cefiderocol-containing groups. A propensity-weighted multiple logistic regression model was calculated to evaluate risk factors for 28-day mortality. Survival curves were calculated using the Kaplan-Meier method. Results: 121 patients were enrolled, 55 were treated with cefiderocol- and 66 with non-cefiderocol-containing regimens. The 28-day all-cause mortality was 56% (68/121). A statistically significant difference in 28-day mortality was found between cefiderocol- and non-cefiderocol- containing regimens groups (44% versus 67%, P=0.011). In the propensity-adjusted multiple logistic regression, cefiderocol (OR 0.35 95% CI 0.14, 0.83) was a predictor of 28-day survival, Charlson comorbidity index (OR 1.36 95% CI 1.16, 1.78), SOFA score (OR 1.24 95% CI 1.09, 1.57) and septic shock (OR 3.71 95% CI 1.44, 12.73) were all associated with increased 28-day mortality. Conclusion: Cefiderocol-containing regimens were associated with reduced 28-day mortality in CRAB-VAP. The sample size and the observational design limit the study's conclusions. Future RCTs are needed to establish cefiderocol's definite role in these infections.