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. 2024 Nov 29;23(1):104.
doi: 10.1186/s12941-024-00763-7.

Transmission cluster of cefiderocol-non-susceptible carbapenem-resistant Acinetobacter baumannii in cefiderocol-naïve individuals

Claudia Alteri #  1   2 , Antonio Teri #  3 , Maria Francesca Liporace  3 , Antonio Muscatello  4 , Leonardo Terranova  5 , Margherita Carnevale Schianca  5 , Federica Salari  6 , Beatrice Silvia Orena  3 , Flaminia Gentiloni Silverj  7 , Mara Bernazzani  7 , Simona Biscarini  4 , Giulia Renisi  4 , Lisa Cariani  3 , Caterina Matinato  3 , Ciro Canetta  8 , Alessandra Bandera  4   9 , Annapaola Callegaro  3
Affiliations

Transmission cluster of cefiderocol-non-susceptible carbapenem-resistant Acinetobacter baumannii in cefiderocol-naïve individuals

Claudia Alteri et al. Ann Clin Microbiol Antimicrob. .

Abstract

Background: During prolonged FDC therapy, the emergence of FDC non-susceptibility in CRAB has been reported. Here, we report a transmission cluster of FDC-non-susceptible CRAB in four patients, all naïve to FDC treatment, characterized by a premature stop codon and amino acid deletion in the PirA protein.

Methods: CRAB strains obtained from patients admitted in a single medicine ward of the IRCCS Fondazione Ospedale Maggiore Policlinico between March and July 2024 were analyzed by WGS and antimicrobial susceptibility testing. Phylogenetic analysis was used to assess their genetic relatedness.

Results: Between March and July 2024, an outbreak of 33 CRAB was observed among hospitalized patients in a single ward at IRCCS. Genomic analysis, available in 29 cases, revealed that 24 isolates belonged to ST208/1806, 4 to ST369, and one to ST195/1816 (according to the Oxford scheme). FDC susceptibility was affected only in the four ST369 isolates (Kirby-Bauer disk diffusion diameter: 13 mm; UMIC® method MIC: 4 mg/L), all characterized by a premature stop codon followed by a 52 amino acid deletion located between the amino acids 377 and 428 of the siderophore-drug receptor PirA. No other relevant mutations were detected in the iron-uptake genes. Core-genome ML tree including ST369 reference strains revealed that the four ST369 isolates were highly related and formed a distinct cluster (SNP distance: 3 [IQR: 1-6]). Of note, the four isolates were collected from four FDC-naïve individuals, two experiencing a CRAB-mediated infection.

Conclusions: Our findings alert about the circulation of clones carrying modified siderophore-drug receptors without evidence of previous FDC treatment and support the importance of testing FDC susceptibility appropriately before its administration.

Keywords: Antimicrobial resistance; CRAB; Cefiderocol; ESKAPEs; Healthcare-associated infections; Surveillance.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethical approval and patients’ written informed consent were not required since it is a retrospective study of bacterial isolates using aggregate clinical data. Consent for publication: All authors approved the manuscript. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Amino acid alignment of the wild-type PirA and the mutated PirA, detected in the transmission chain of the four ST369 CRABs. An asterisk shows the premature stop codon. The deletion at amino acids 376–428 is shown by dashes
Fig. 2
Fig. 2
Estimated maximum likelihood phylogenetic analysis of the four Cefiderocol (FDC) non-susceptible carbapenem-resistant Acinetobacter baumannii isolates. The maximum likelihood was inferred from a core genome alignment of 3,344,425 bp. The phylogeny was estimated with IqTree using the best-fit model of nucleotide substitution HKY + F with 1,000 replicates and fast bootstrapping. The numbers on leaves represent the sample IDs, and bootstrap values are shown on branches. Information regarding the samples was reported: date of isolation, the sequence type (ST), capsular locus (K locus) and lipooligosaccharide outer core (OC locus), the presence (solid squares) or absence of antimicrobial resistance genes, the presence of deletion in pirA gene, the Cefiderocol-non-susceptibility, tested by disk diffusion (according to the last EUCAST guidelines, https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_14.0_Breakpoint_Tables.pdf) and the minimal inhibitory concentration (MIC) value by the UMIC (Bruker) commercial test
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