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Observational Study
. 2022 May 17;66(5):e0214221.
doi: 10.1128/aac.02142-21. Epub 2022 Mar 21.

Cefiderocol- Compared to Colistin-Based Regimens for the Treatment of Severe Infections Caused by Carbapenem-Resistant Acinetobacter baumannii

Marco Falcone  1 , Giusy Tiseo  1 , Alessandro Leonildi  2 , Leonardo Della Sala  1 , Alessandra Vecchione  2 , Simona Barnini  2 , Alessio Farcomeni  3 , Francesco Menichetti  1
Affiliations
Observational Study

Cefiderocol- Compared to Colistin-Based Regimens for the Treatment of Severe Infections Caused by Carbapenem-Resistant Acinetobacter baumannii

Marco Falcone et al. Antimicrob Agents Chemother. .

Abstract

Cefiderocol may represent a therapeutic option for carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but clinical data are limited. This is an observational retrospective study conducted in the University Hospital of Pisa including consecutive patients with CRAB infections (January 2020 to August 2021). Patients were divided in two study groups according to the antibiotic treatment received: cefiderocol- and colistin-containing regimens. The primary outcome was the 30-day mortality. A Cox regression analysis was performed to identify factors independently associated with 30-day mortality. A propensity score analysis using inverse probability of treatment weighting (IPTW) was also performed. A total of 124 patients were included: 47 (37.9%) received cefiderocol, while 77 (62.1%) colistin-containing regimens. Overall, 79 (63.7%) patients had a bloodstream infection (BSI), 35 (28.5%) a ventilator-associated pneumonia (VAP) and 10 (8.1%) other infections. Thirty-day mortality was higher in patients receiving colistin- compared to those who received cefiderocol-containing regimens (55.8% versus 34%, P = 0.018). This difference was confirmed in patients with BSI, but not in those with VAP. On multivariable analysis, septic shock, SOFA score, and age were independently associated with 30-day mortality, while cefiderocol therapy was protective in an IPTW analysis (Hazard ratio 0.44, 95% confidence interval 0.22-0.66, P < 0.001). Nephrotoxicity was more common in the colistin group. Microbiological failure occurred in 17.4% of patients receiving cefiderocol versus 6.8% of those receiving colistin (P = 0.079). Among 8 cases in the cefiderocol group who experienced microbiological failure, 4 (50%) developed resistance to cefiderocol. Cefiderocol represents a promising therapeutic option in patients with severe CRAB infections. Randomized clinical trial in this specific patient population should confirm our findings.

Keywords: Acinetobacter baumannii; antibiotic resistance; bloodstream infections; cefiderocol; colistin; multidrug resistance; pneumonia; sepsis; ventilator-associated pneumonia.

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Conflict of interest statement

The authors declare a conflict of interest. M.F. received grants and/or speaker honoraria from MSD, Angelini, Shionogi, Pfizer, Menarini, Gilead and Nordic Pharma. F.M. has participated in advisory boards and/or received speaker honoraria from Angelini, Correvio, Merck Sharp & Dohme (MSD), Nordic Pharma, Pfizer, Astellas, Gilead, Bristol-Myers Squibb (BMS), Janssen, ViiV, bioMérieux, Biotest, Becton Dickinson, Pfizer, and Shionogi. Declared conflicts of interest are outside the submitted work and did not affect the scientific objectivity of this study. The other authors have none to declare.

Figures

FIG 1
FIG 1
Study flow chart. CRAB, carbapenem-resistant Acinetobacter baumannii.
FIG 2
FIG 2
Fourteen- and 30-days mortality in patients with bloodstream infection (BSI) and ventilator-associated pneumonia (VAP). FDC cefiderocol.
FIG 3
FIG 3
Unadjusted (A) and IPTW-adjusted (B) Kaplan Meier survival curves of patients who received cefiderocol- and those who received colistin-containing regimens. CRAB, carbapenem-resistant Acinetobacter baumannii.
See this image and copyright information in PMC

Comment in

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