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

Abstract

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.

Cefiderocol in Difficult-to-Treat Nf-GNB in ICU Settings

“…This study showed a higher, yet not statistically significant, mortality rate in the cefiderocol group compared to the colistin group (51% vs. 37%, p = 0.130). These results were confirmed in several study and meta-analysis, which reported better outcomes in the specific setting of Carbapenem-Resistant Acinetobacter baumannii infections with cefiderocol [ 17 – 20 ].…”

Current Therapeutic Approaches for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections

“…While the above two studies [ 33 , 34 ] are the only randomised studies until today, there have been a significant number of studies performed in recent years [ 36 , 37 , 38 , 39 , 40 , 41 , 42 ], and we present these data in Table 2 . Most of these studies were conducted in Italy and are retrospective in nature.…”

“…Most of these studies were conducted in Italy and are retrospective in nature. A total of 744 patients were included in the studies in the table [ 33 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ] that addressed the therapeutic management of VAP and bloodstream carbapenem-resistant A. baumannii (CRAB) infections. When examining the mortality of patients that received a cefiderocol-containing regimen versus a comparator regimen that did not contain cefiderocol, mortality was observed in 152 out of the 367 patients (41.4%) that received cefiderocol versus 247 out of the 430 patients (57.4%) that received a comparator antibiotic.…”

“…Nevertheless, there is already a significant number of trials (although non-randomised) presented herein that are in favour of cefiderocol. Indeed, the comparative studies by Pascale et al [ 36 ], Falcone et al [ 37 ]., Mazzitelli et al [ 38 ], Bavaro et al [ 39 ], Rando et al [ 40 ], Dalfino et al [ 41 ] and Russo et al [ 42 ] included 637 patients, and 306 of them received cefiderocol for A. baumannii infections with favourable clinical outcomes.…”

Treatment and Management of Acinetobacter Pneumonia: Lessons Learned from Recent World Event

“… 198 , 199 Cefiderocol, a novel β-lactam with activity against CRAB, has shown promise, although its role in treating pulmonary infections caused by this pathogen remains controversial due to limited evidence. 200 , 201 …”