Extreme resistance to the novel siderophore-cephalosporin cefiderocol in an extensively drug-resistant Klebsiella pneumoniae strain causing fatal pneumonia with sepsis: genomic analysis and synergistic combinations for resistance reversal

Cefiderocol (CFDC) is the first-in-class siderophore-cephalosporin. Klebsiella pneumoniae strain that is extremely resistant to CFDC (MIC: 256 µg/ml) was isolated for the first time in the United Arab Emirates from a patient with pneumonia and sepsis. It belonged to sequence-type 14 (ST14), with a n...

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Veröffentlicht in:European journal of clinical microbiology & infectious diseases 2023-11, Vol.42 (11), p.1395-1400
Hauptverfasser: Daoud, Land, Allam, Mushal, Collyns, Timothy, Ghazawi, Akela, Saleem, Aqeel, Al-Marzooq, Farah
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Sprache:eng
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Zusammenfassung:Cefiderocol (CFDC) is the first-in-class siderophore-cephalosporin. Klebsiella pneumoniae strain that is extremely resistant to CFDC (MIC: 256 µg/ml) was isolated for the first time in the United Arab Emirates from a patient with pneumonia and sepsis. It belonged to sequence-type 14 (ST14), with a novel core genome ST. Resistance was driven by the co-expression of β-lactamases ( bla NDM-1 , bla OXA-232 and bla CTX-M-15 ) and a mutation in catecholate-siderophore receptor, utilized by CFDC to enter the bacterial cell. Synergistic combinations (β-lactamase inhibitors, aztreonam plus CFDC) re-sensitized the bacteria to CFDC. Although CFDC resistance is multifactorial, the combination with β-lactamase inhibitors represents a promising approach in resistance reversal for fighting superbugs.
ISSN:0934-9723
1435-4373
DOI:10.1007/s10096-023-04671-0