TY - JOUR
T1 - Extreme resistance to the novel siderophore-cephalosporin cefiderocol in an extensively drug-resistant Klebsiella pneumoniae strain causing fatal pneumonia with sepsis
T2 - genomic analysis and synergistic combinations for resistance reversal
AU - Daoud, Land
AU - Allam, Mushal
AU - Collyns, Timothy
AU - Ghazawi, Akela
AU - Saleem, Aqeel
AU - Al-Marzooq, Farah
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
KW - Antibiotic resistance
KW - Cefiderocol
KW - Klebsiella pneumoniae
KW - ST14
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U2 - 10.1007/s10096-023-04671-0
DO - 10.1007/s10096-023-04671-0
M3 - Article
C2 - 37828413
AN - SCOPUS:85174014387
SN - 0934-9723
VL - 42
SP - 1395
EP - 1400
JO - European Journal of Clinical Microbiology and Infectious Diseases
JF - European Journal of Clinical Microbiology and Infectious Diseases
IS - 11
ER -
