Mutations in genes related to iron transfer systemsP. aeruginosa
A. baumaniiIn vitro-induced mutants or isogenic strainspiuA [50,51], piuD [51], pirA [50,51]piuA or piuD with deletion of pirA—the increase was 32-fold and 64-fold, respectively [50,51].Clinical isolatespiuDC [52], piuA [53,54,55,56], pirR [53], pirA [54,57]Deletion of piuDC and the ampC regulator ampD led to co-resistance to cefiderocol and ceftazidime/avibactam in P. aeruginosa [52].
Substitution of L147F in ampC gene together with mutations in piuA and pirR genes led to acquired resistance to cefiderocol and ceftolozane/tazobactam in P. aeruginosa [53].
piuA deficiency together with reduced expression of pirA in cefiderocol-resistant A. baumannii clinical isolate [54].EnterobacteralesIn vitro-induced mutants or isogenic strainscirA [58,59], fiu [50],
tonB, exbB, exbD, fecA, fbpA, efeo [60,61,62]Loss of fiu resulted in two-fold increase of cefiderocol MIC, increasing up to 16-fold when combined with deletion of cirA [50].Clinical isolatesCirA [63,64,65,66,67]Most cefiderocol-resistant K. pneumoniae or E. coli clinical isolates presenting mutations in cirA were also producers of NDM metallo β-lactamase [63,64,65,66,67].S. maltophiliaIn vitro-induced mutants or isogenic strainstonB, exbD, smlat1148, cirA [68,69]Expression of metallo-β-lactamasesEnterobacterales
P. aeruginosaIn vitro-induced mutants or isogenic strainsbla_NDM-type [70,71,72,73], bla_SPM−1 [72]≥8-fold increase of cefiderocol MIC was observed when both serine- and metallo-type β-lactamase inhibitors were added in E. coli isogenic strains [70].EnterobacteralesClinical isolatesbla_NDM-type [63,64,65,66,67,70,74,75]The combined effect of NDM expression and cirA deficiency in K. pneumoniae and E. coli was associated with cefiderocol resistance [63,64,65,66,67,74].Expression of KPC variantsEnterobacteralesIn vitro-induced mutants or isogenic strainsbla_KPC−31, bla_KPC−33,
bla_KPC−25, bla_KPC−29, bla_KPC−39, bla_KPC−44, bla_KPC−41, bla_KPC−50 [76,77]K. pneumoniaeClinical isolatesbla_KPC−31, bla_KPC−33,
bla_KPC−41, bla_KPC−50,
bla_KPC−121, bla_KPC−109, bla_KPC−203, bla_KPC−216 [77,78,79,80,81,82]Expression of OXA-like β-lactamasesA. baumannii,
E. coli,
P. aeruginosaIn vitro-induced mutants or isogenic strainsbla_OXA−427 [71,72,83]EnterobacteralesClinical isolatesbla_OXA−427 [83]Expression of ampC variantsE. coliIn vitro-induced mutants or isogenic strainsA292_L293del bla_ampC [84]

bla_PDC−30 [85]

E. cloacae complex, E. coli, P. aeruginosaClinical isolatesA292_L293del bla_ampC [84], bla_CMY−185 [86]
bla_CMY−186 [87], L147F bla_PDC−191 [53]
E247K bla_PDC-like [88]
bla_PDC−30 [85]SNPs identified in genes belonging to TonB-dependent receptors (TBDRs) and in the chromosomal ampC β-lactamase gene were associated with in vivo emergence of cefiderocol resistance in P. aeruginosa [53].
Mutations in ampD G116D and in efflux pump system (MexR A66V, MexR L57D) were associated with increases in cefiderocol MICs in P. aeruginosa [88].Expression of other β-lactamasesE. coli,
P. aeruginosa,
A. baumannii,In vitro-induced mutants or isogenic strainsbla_PER-like [70,71,72]K. pneumoniaeClinical isolatesbla_PER−1 [70], bla_PER-like [89], amplification of bla_SHV−12 [90]Mutations in penicillin-binding proteinsA. baumanni,
E. coliClinical isolatesPBP−3 gene (ftsI)
[17,54,55,62,63,85]PBP-3 mutant (insYRIN) alone was not sufficient to cause cefiderocol resistance in E. coli, but its combination with NDM expression and/or cirA deletion was required [66].
Combination of NDM-5 expression with mutated ftsI and cirA genes was observed in cefiderocol resistance E. coli isolates [63].Porin lossK. pneumoniae,
E. cloacae,
P. aeruginosaClinical isolatesompK35, ompK36, ompK37 [91,92], ompC and ompF [91], oprD [17]Efflux pump overexpressionP. aeruginosa,
S. maltophilia,
K. pneumoniae, A. xylosoxidansClinical isolatesmexAB–oprM [93], smeDEF [70], sugE, chrA [92] axyABM [94]