TY - JOUR
T1 - CefiderocolFinder
T2 - a tool for detecting genetic adaptations implicated in cefiderocol resistance
AU - van den Brand, Bryan
AU - Notermans, Daan W
AU - Verkaik, Nelianne J
AU - Lansu, Simon
AU - Rossen, John W A
AU - Hendrickx, Antoni P A
AU - van Arkel, A L E
AU - Leversteijn-van Hall, M A
AU - van den Bijllaardt, W
AU - van Mansfeld, R
AU - van Dijk, K
AU - Zwart, B
AU - Diederen, B M W
AU - Berkhout, H
AU - Ott, A
AU - Waar, K
AU - Ang, W
AU - da Silva, J
AU - Vlek, A L M
AU - Stohr, J J J M
AU - Bode, L G M
AU - Jansz, A
AU - Paltansing, S
AU - van Griethuysen, A J
AU - Lo Ten Foe, J R
AU - van Trijp, M J C A
AU - Wong, M
AU - Muller, A E
AU - van der Linden, M P M
AU - van Rijn, M
AU - Debast, S B
AU - Kolwijck, E
AU - Al Naiemi, N
AU - Schulin, T
AU - Dinant, S
AU - van Mens, S P
AU - Melles, D C
AU - Stuart, J W T Cohen
AU - Gruteke, P
AU - van Dam, A P
AU - Rahamat-Langendoen, J
AU - Maraha, B
AU - Sinnige, J C
AU - van der Vorm, E
AU - de Graaf, M
AU - de Jong, E
AU - Heikens, E
AU - Troelstra, A
AU - de Vries, J
AU - van Dam, D W
N1 - Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.
PY - 2026/4
Y1 - 2026/4
N2 - OBJECTIVES: Cefiderocol is a novel last-resort cephalosporin antimicrobial increasingly used for difficult-to-treat infections by multidrug-resistant microorganisms (MDRO), and is effective against carbapenem-resistant Enterobacterales and Pseudomonas species. Multiple chromosomally encoded genetic determinants have been implicated in cefiderocol resistance, including mutations, deletions and/or frameshifts. However, identification of these determinants remains labour-intensive and time-consuming. Therefore, we share CefiderocolFinder, a bioinformatics pipeline to detect 25 genetic adaptations implicated in cefiderocol resistance from short-read whole genome sequencing (WGS) data.METHODS: CefiderocolFinder was built using Python, supports WGS data of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, and contains alignment, variant calling, annotation and filtering steps. A short-read WGS dataset (n=98) and validation WGS dataset (n=21) with cefiderocol antimicrobial susceptibility testing (AST) results was used to interpret and validate CefiderocolFinder.RESULTS: Using CefiderocolFinder, with WGS data from 98 MDRO collected from Ukrainian patients in 2022, six unique genetic adaptations were detected. These adaptations were associated with higher MICs in AST with cefiderocol. Loss of function mutations were found in the siderophore receptor cirA, the general porins oprD, ompC, ompF, negative regulator of the acrAB-tolC efflux operon acrR and a conservative in-frame insertion YRIN in ftsI encoding for Penicillin-binding protein 3. The adaptations were identified in 12 of 16 E. coli (75%), 1 of 60 K. pneumoniae (1%), 6 of 17 P. aeruginosa (35%) and 0 of 5 A. baumannii (0%) isolates. CefiderocolFinder was validated using publicly available datasets.CONCLUSIONS: CefiderocolFinder provides context to corroborate phenotypical AST from WGS data, especially when the result is in an area of technical uncertainty. For E. coli, CefiderocolFinder can be a valuable tool for informing the clinician of specific genetic adaptations associated with resistance to cefiderocol, where for K. pneumoniae and P. aeruginosa the prediction of phenotypical resistance can be improved. CefiderocolFinder is available open access at http://github.com/Bryan-vd-Brand/CefiderocolFinder.
AB - OBJECTIVES: Cefiderocol is a novel last-resort cephalosporin antimicrobial increasingly used for difficult-to-treat infections by multidrug-resistant microorganisms (MDRO), and is effective against carbapenem-resistant Enterobacterales and Pseudomonas species. Multiple chromosomally encoded genetic determinants have been implicated in cefiderocol resistance, including mutations, deletions and/or frameshifts. However, identification of these determinants remains labour-intensive and time-consuming. Therefore, we share CefiderocolFinder, a bioinformatics pipeline to detect 25 genetic adaptations implicated in cefiderocol resistance from short-read whole genome sequencing (WGS) data.METHODS: CefiderocolFinder was built using Python, supports WGS data of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, and contains alignment, variant calling, annotation and filtering steps. A short-read WGS dataset (n=98) and validation WGS dataset (n=21) with cefiderocol antimicrobial susceptibility testing (AST) results was used to interpret and validate CefiderocolFinder.RESULTS: Using CefiderocolFinder, with WGS data from 98 MDRO collected from Ukrainian patients in 2022, six unique genetic adaptations were detected. These adaptations were associated with higher MICs in AST with cefiderocol. Loss of function mutations were found in the siderophore receptor cirA, the general porins oprD, ompC, ompF, negative regulator of the acrAB-tolC efflux operon acrR and a conservative in-frame insertion YRIN in ftsI encoding for Penicillin-binding protein 3. The adaptations were identified in 12 of 16 E. coli (75%), 1 of 60 K. pneumoniae (1%), 6 of 17 P. aeruginosa (35%) and 0 of 5 A. baumannii (0%) isolates. CefiderocolFinder was validated using publicly available datasets.CONCLUSIONS: CefiderocolFinder provides context to corroborate phenotypical AST from WGS data, especially when the result is in an area of technical uncertainty. For E. coli, CefiderocolFinder can be a valuable tool for informing the clinician of specific genetic adaptations associated with resistance to cefiderocol, where for K. pneumoniae and P. aeruginosa the prediction of phenotypical resistance can be improved. CefiderocolFinder is available open access at http://github.com/Bryan-vd-Brand/CefiderocolFinder.
U2 - 10.1016/j.cmi.2025.12.009
DO - 10.1016/j.cmi.2025.12.009
M3 - Article
C2 - 41429344
SN - 1198-743X
VL - 32
SP - 610
EP - 617
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
IS - 4
ER -