TY - JOUR
T1 - Cefiderocol antimicrobial susceptibility testing considerations
T2 - The achilles' heel of the trojan horse?
AU - Simner, Patricia J.
AU - Patel, Robin
N1 - Funding Information:
Patricia J. Simner served as an advisory board member as part of a microbiology panel for Shionogi Inc. Patricia J. Simner reports grants and personal fees from Accelerate Diagnostics, OpGen Inc. and BD Diagnostics, grants from bioMérieux, Inc., Affinity Biosensors, and Hardy Diagnostics, and personal fees from Roche Diagnostics, outside the submitted work. Patricia J. Simner receives travel reimbursement from ASM, CAP, and CLSI. Robin Patel reports grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics, Ltd., and Shionogi. Robin Patel reports grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics, Ltd., and Shionogi. Robin Patel is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST and Qvella; monies are paid to Mayo Clinic. In addition, Robin Patel has a patent on Bordetella pertussis/Bordetella parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. Robin Patel receives travel reimbursement from ASM and IDSA, an editor’s stipend from IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course.
Funding Information:
Patricia J. Simner served as an advisory board member as part of a microbiology panel for Shionogi Inc. Patricia J. Simner reports grants and personal fees from Accelerate Diagnostics, OpGen Inc. and BD Diagnostics, grants from bioM?rieux, Inc., Affinity Biosensors, and Hardy Diagnostics, and personal fees from Roche Diagnostics, outside the submitted work. Patricia J. Simner receives travel reimbursement from ASM, CAP, and CLSI. Robin Patel reports grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics, Ltd., and Shionogi. Robin Patel reports grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics, Ltd., and Shionogi. Robin Patel is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST and Qvella; monies are paid to Mayo Clinic. In addition, Robin Patel has a patent on Bordetella pertussis/Bordetella parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued. Robin Patel receives travel reimbursement from ASM and IDSA, an editor's stipend from IDSA, and honoraria from the NBME, Up-to-Date and the Infectious Diseases Board Review Course.
Publisher Copyright:
Copyright © 2020 American Society for Microbiology. All Rights Reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Cefiderocol (formerly S-649266) is a novel siderophore-conjugated cephalosporin with activity against a broad array of multidrug-resistant (MDR), aerobic Gram-negative bacilli. The siderophore component binds iron and uses active iron transport for drug entry into the bacterial periplasmic space. The cephalosporin moiety is the active antimicrobial component, structurally resembling a hybrid between ceftazidime and cefepime. Like other β-lactam agents, the principal bactericidal activity of cefiderocol occurs via inhibition of bacterial cell wall synthesis by binding of penicillin-binding proteins (PBPs) and inhibiting peptidoglycan synthesis, leading to cell death. Iron concentrations need to be taken into consideration when in vitro antimicrobial susceptibility to cefiderocol is determined. Broth microdilution (BMD) and disk diffusion methods have been developed to determine in vitro activity of cefiderocol. For BMD, cation-adjusted Mueller-Hinton broth (CAMHB) requires iron depletion to provide MICs predictive of in vivo activity. A method to prepare iron-depleted CAMHB (ID-CAMHB) has been described by the Clinical and Laboratory Standards Institute (CLSI). For disk diffusion, standard Mueller-Hinton agar is recommended, presumably because iron is bound in the medium. Currently, clinical FDA and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and investigational (research-use-only) CLSI breakpoints exist for interpreting cefiderocol susceptibility results for certain Gram-negative bacilli. Cefiderocol does not have clinically relevant activity against Gram-positive or anaerobic organisms. FDA or EUCAST breakpoints should be applied to interpret results for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex for patient care until the investigational status has been removed from CLSI breakpoints. Further clinical outcome data are required to assess the effectiveness of cefiderocol for treatment of other Acinetobacter species (non-baumannii complex) and Stenotrophomonas maltophilia at this time, and, as such, antimicrobial susceptibility testing of these organisms should be limited to research use in the scenario of limited treatment options.
AB - Cefiderocol (formerly S-649266) is a novel siderophore-conjugated cephalosporin with activity against a broad array of multidrug-resistant (MDR), aerobic Gram-negative bacilli. The siderophore component binds iron and uses active iron transport for drug entry into the bacterial periplasmic space. The cephalosporin moiety is the active antimicrobial component, structurally resembling a hybrid between ceftazidime and cefepime. Like other β-lactam agents, the principal bactericidal activity of cefiderocol occurs via inhibition of bacterial cell wall synthesis by binding of penicillin-binding proteins (PBPs) and inhibiting peptidoglycan synthesis, leading to cell death. Iron concentrations need to be taken into consideration when in vitro antimicrobial susceptibility to cefiderocol is determined. Broth microdilution (BMD) and disk diffusion methods have been developed to determine in vitro activity of cefiderocol. For BMD, cation-adjusted Mueller-Hinton broth (CAMHB) requires iron depletion to provide MICs predictive of in vivo activity. A method to prepare iron-depleted CAMHB (ID-CAMHB) has been described by the Clinical and Laboratory Standards Institute (CLSI). For disk diffusion, standard Mueller-Hinton agar is recommended, presumably because iron is bound in the medium. Currently, clinical FDA and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints and investigational (research-use-only) CLSI breakpoints exist for interpreting cefiderocol susceptibility results for certain Gram-negative bacilli. Cefiderocol does not have clinically relevant activity against Gram-positive or anaerobic organisms. FDA or EUCAST breakpoints should be applied to interpret results for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex for patient care until the investigational status has been removed from CLSI breakpoints. Further clinical outcome data are required to assess the effectiveness of cefiderocol for treatment of other Acinetobacter species (non-baumannii complex) and Stenotrophomonas maltophilia at this time, and, as such, antimicrobial susceptibility testing of these organisms should be limited to research use in the scenario of limited treatment options.
KW - Antimicrobial susceptibility testing
KW - Broth microdilution
KW - Cefiderocol
KW - Disk diffusion
UR - http://www.scopus.com/inward/record.url?scp=85097450851&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097450851&partnerID=8YFLogxK
U2 - 10.1128/JCM.00951-20
DO - 10.1128/JCM.00951-20
M3 - Review article
C2 - 32727829
AN - SCOPUS:85097450851
SN - 0095-1137
VL - 59
JO - Journal of clinical microbiology
JF - Journal of clinical microbiology
IS - 1
M1 - e00951-20
ER -