TY - JOUR
T1 - Comparison of agar dilution to broth microdilution for testing in vitro activity of cefiderocol against gram-negative bacilli
AU - Albano, Mariana
AU - Karau, Melissa J.
AU - Schuetz, Audrey N.
AU - Patel, Robin
N1 - Publisher Copyright:
Copyright © 2020 Albano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
PY - 2021/1
Y1 - 2021/1
N2 - Cefiderocol (CFDC) is a siderophore cephalosporin with activity against Gram-negative bacterial species that are resistant to carbapenems and other drugs. The MICs of CFDC were determined for 610 Gram-negative bacilli, including 302 multinational Enterobacterales isolates with characterized mechanisms of beta-lactam resistance, 180 clinical isolates from the Mayo Clinic and Mayo Clinic Laboratories not characterized for specific resistance mechanisms, and 128 isolates with CFDC MICs of ≥8 μg/ml obtained from International Health Management Associates, Inc. (IHMA, Schaumburg, IL). Broth microdilution using standard cation-adjusted Mueller-Hinton broth (BMD) and iron-depleted cation-adjusted Mueller-Hinton broth (ID-BMD), and agar dilution (AD) using standard Mueller-Hinton agar were performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. MICs were interpreted according to the investigational CLSI, FDA, and EUCAST breakpoints, and results were compared. MICs inhibiting 50 and 90% of organisms (MIC50 and MIC90, respectively), essential agreement (EA), categorical agreement (CA), and error of different types were determined. Results showed considerable discordance between AD and ID-BMD. CFDC showed low EA and CA rates and high error rates for AD in comparison to ID-BMD. Overall, this study does not support use of standard AD for determining CFDC MICs.
AB - Cefiderocol (CFDC) is a siderophore cephalosporin with activity against Gram-negative bacterial species that are resistant to carbapenems and other drugs. The MICs of CFDC were determined for 610 Gram-negative bacilli, including 302 multinational Enterobacterales isolates with characterized mechanisms of beta-lactam resistance, 180 clinical isolates from the Mayo Clinic and Mayo Clinic Laboratories not characterized for specific resistance mechanisms, and 128 isolates with CFDC MICs of ≥8 μg/ml obtained from International Health Management Associates, Inc. (IHMA, Schaumburg, IL). Broth microdilution using standard cation-adjusted Mueller-Hinton broth (BMD) and iron-depleted cation-adjusted Mueller-Hinton broth (ID-BMD), and agar dilution (AD) using standard Mueller-Hinton agar were performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. MICs were interpreted according to the investigational CLSI, FDA, and EUCAST breakpoints, and results were compared. MICs inhibiting 50 and 90% of organisms (MIC50 and MIC90, respectively), essential agreement (EA), categorical agreement (CA), and error of different types were determined. Results showed considerable discordance between AD and ID-BMD. CFDC showed low EA and CA rates and high error rates for AD in comparison to ID-BMD. Overall, this study does not support use of standard AD for determining CFDC MICs.
KW - Agar dilution
KW - Broth microdilution
KW - Cefiderocol
KW - Enterobacterales
KW - Gram-negative bacilli
KW - Gram-negative bacteria
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U2 - 10.1128/JCM.00966-20
DO - 10.1128/JCM.00966-20
M3 - Article
C2 - 32967901
AN - SCOPUS:85098523684
SN - 0095-1137
VL - 59
JO - Journal of clinical microbiology
JF - Journal of clinical microbiology
IS - 1
M1 - e00966-20
ER -