Rapid Development of cefiderocol resistance in a carbapenem-resistant Pseudomonas aeruginosa isolate associated with mutations in the pyoverdine biosynthesis pathway

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@article{b2f8d96cdd5f4ff6a9d1a713888c4a20,
title = "Rapid Development of cefiderocol resistance in a carbapenem-resistant Pseudomonas aeruginosa isolate associated with mutations in the pyoverdine biosynthesis pathway",
abstract = "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-na{\"i}ve 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.",
author = "Luise Brakert and Laura Berneking and Anna Both and Benjamin Berinson and Jiabin Huang and Martin Aepfelbacher and Christine Wolschke and Dominic Wichmann and Holger Rohde",
note = "Copyright {\textcopyright} 2023. Published by Elsevier Ltd.",
year = "2023",
month = sep,
doi = "10.1016/j.jgar.2023.06.003",
language = "English",
volume = "34",
pages = "59--62",
journal = "J GLOB ANTIMICROB RE",
issn = "2213-7165",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

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 -