OXA-carbapenemases and mutations within PBPs in ST2 carbapenem-resistant A. baumannii: Evaluating the efficacy of cefiderocol and ampicillin-sulbactam combination therapy

Objectives: Carbapenem-resistant Acinetobacter baumannii (A. baumannii; CRAB) isolates represent a serious public health concern. Recently, a novel molecule, the cefiderocol (FDC), has emerged as a promising therapeutic option for CRAB infections. In the present study, we analysed the genomes of five A. baumannii ST2 isolates from four hospitalized patients. All patients were treated with FDC and an ampicillin/sulbactam (AMP/SUL) combination. Methods: Whole-genome sequencing of the five CRAB isolates was performed using an Illumina MiSeq instrument. A detailed bioinformatic analysis was carried out to acquire information about genotyping, antimicrobial resistance genes (ARGs), virulence associated genes (VAGs), single nucleotide polymorphisms (SNPs), and the phylogenetic tree of the five CRAB isolates. Results: Among the five CRAB isolates, only three (Ab.2, Ab.3, and Ab.4) exhibited resistance to FDC. The genomes of all isolates were highly similar, and multilocus sequence typing (MLST) analysis indicated they all belong to sequence type 2 (ST2), corresponding to international clone 2. Phylogenetic analysis suggests that isolates Ab.2, Ab.3, and Ab.4 may share a common ancestor or be linked by a possible transmission event. In contrast, isolates Ab.1 and Ab.5 were more divergent from the other three. Nevertheless, all five isolates harboured the same ARGs and VAGs. The OXA-23, OXA-66, and ADC-25 β-lactamases were detected in all strains. The FDC-non-susceptible isolates showed a K235N/H370Y double mutation within PBP3, along with a G370C substitution in PBP1a. Conclusions: The four clinical cases described in this study represent an important example of the efficacy and good practice of FDC plus AMP/SUL combination in the treatment of critical patients suffering from CRAB infections. © 2025 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.