Annals of clinical microbiology and antimicrobials · 2024
Transmission cluster of cefiderocol-non-susceptible carbapenem-resistant Acinetobacter baumannii in cefiderocol-naïve individuals.
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Alteri Claudia, Teri Antonio, Liporace Maria Francesca, Muscatello Antonio, Terranova Leonardo, Schianca Margherita Carnevale, Salari Federica, Orena Beatrice Silvia, Silverj Flaminia Gentiloni, Bernazzani Mara, Biscarini Simona, Renisi Giulia, Cariani Lisa, Matinato Caterina, Canetta Ciro, Bandera Alessandra, Callegaro Annapaola
Аннотация
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.
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.