Rapid Development of cefiderocol resistance in a carbapenem-resistant Pseudomonas aeruginosa isolate associated with mutations in the pyoverdine biosynthesis pathway
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Rapid Development of cefiderocol resistance in a carbapenem-resistant Pseudomonas aeruginosa isolate associated with mutations in the pyoverdine biosynthesis pathway. / Brakert, Luise; Berneking, Laura; Both, Anna; Berinson, Benjamin; Huang, Jiabin; Aepfelbacher, Martin; Wolschke, Christine; Wichmann, Dominic; Rohde, Holger.
in: J GLOB ANTIMICROB RE, Jahrgang 34, 09.2023, S. 59-62.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › Kurzpublikation › Forschung › Begutachtung
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T1 - Rapid Development of cefiderocol resistance in a carbapenem-resistant Pseudomonas aeruginosa isolate associated with mutations in the pyoverdine biosynthesis pathway
AU - Brakert, Luise
AU - Berneking, Laura
AU - Both, Anna
AU - Berinson, Benjamin
AU - Huang, Jiabin
AU - Aepfelbacher, Martin
AU - Wolschke, Christine
AU - Wichmann, Dominic
AU - Rohde, Holger
N1 - Copyright © 2023. Published by Elsevier Ltd.
PY - 2023/9
Y1 - 2023/9
N2 - Here we report the in vivo development of cefiderocol resistance within 11 days after therapy initiation in a critically ill patient with bloodstream infection, infection of peri-anal fistula, and pneumonia caused by a VIM-2 harbouring, carbapenem-resistant Pseudomonas aeruginosa. Compared to a cefiderocol-naïve P. aeruginosa blood culture isolate, agar diffusion susceptibility testing found a reduced cefiderocol inhibition zone diameter in a P. aeruginosa recovered from peri-anal abscess tissue cultures after initiation of cefiderocol therapy. Subsequent whole-genome sequencing suggested that both isolates were of clonal origin. Comparison of genomes found an accumulation of missense mutations within pvdP, pvdE, pvdJ, and pvdD (i.e. genes associated with biosynthesis of pyoverdine), the main siderophore produced by P. aeruginosa. Quantification of pyoverdine production under iron-depleted conditions showed a significantly (P = 0.0003) higher pyoverdine production by the cefiderocol-resistant isolate. While pyoverdine quantity alone appears not to be decisive for cefiderocol resistance, the reported case highlights the potentially rapid emergence of cefiderocol resistance in P. aeruginosa and points towards a potential involvement of iron up-take systems in this process.
AB - Here we report the in vivo development of cefiderocol resistance within 11 days after therapy initiation in a critically ill patient with bloodstream infection, infection of peri-anal fistula, and pneumonia caused by a VIM-2 harbouring, carbapenem-resistant Pseudomonas aeruginosa. Compared to a cefiderocol-naïve P. aeruginosa blood culture isolate, agar diffusion susceptibility testing found a reduced cefiderocol inhibition zone diameter in a P. aeruginosa recovered from peri-anal abscess tissue cultures after initiation of cefiderocol therapy. Subsequent whole-genome sequencing suggested that both isolates were of clonal origin. Comparison of genomes found an accumulation of missense mutations within pvdP, pvdE, pvdJ, and pvdD (i.e. genes associated with biosynthesis of pyoverdine), the main siderophore produced by P. aeruginosa. Quantification of pyoverdine production under iron-depleted conditions showed a significantly (P = 0.0003) higher pyoverdine production by the cefiderocol-resistant isolate. While pyoverdine quantity alone appears not to be decisive for cefiderocol resistance, the reported case highlights the potentially rapid emergence of cefiderocol resistance in P. aeruginosa and points towards a potential involvement of iron up-take systems in this process.
U2 - 10.1016/j.jgar.2023.06.003
DO - 10.1016/j.jgar.2023.06.003
M3 - Short publication
C2 - 37379881
VL - 34
SP - 59
EP - 62
JO - J GLOB ANTIMICROB RE
JF - J GLOB ANTIMICROB RE
SN - 2213-7165
ER -