PMID- 32938734 OWN - NLM STAT- MEDLINE DCOM- 20210623 LR - 20231213 IS - 1098-660X (Electronic) IS - 0095-1137 (Print) IS - 0095-1137 (Linking) VI - 59 IP - 1 DP - 2020 Dec 17 TI - Cefiderocol Antimicrobial Susceptibility Testing against Multidrug-Resistant Gram-Negative Bacilli: a Comparison of Disk Diffusion to Broth Microdilution. LID - 10.1128/JCM.01649-20 [doi] LID - e01649-20 AB - Antimicrobial susceptibility testing (AST) of cefiderocol poses challenges because of its unique mechanism of action (i.e., requiring an iron-depleted state) and due to differences in interpretative criteria established by the Clinical and Laboratory Standards Institute (CLSI), U.S. Food and Drug Administration (FDA), and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Our objective was to compare cefiderocol disk diffusion methods (DD) to broth microdilution (BMD) for AST of Gram-negative bacilli (GNB). Cefiderocol AST was performed on consecutive carbapenem-resistant Enterobacterales (CRE; 58 isolates) and non-glucose-fermenting GNB (50 isolates) by BMD (lyophilized panels; Sensititre; Thermo Fisher) and DD (30 mug; research-use-only [RUO] MASTDISCS and FDA-cleared HardyDisks). Results were interpreted using FDA (prior to 28 September 2020 update), EUCAST, and investigational CLSI breakpoints (BPs). Categorical agreement (CA), minor errors (mE), major errors (ME), and very major errors (VME) were calculated for DD methods. The susceptibilities of all isolates by BMD were 72% (FDA), 75% (EUCAST) and 90% (CLSI). For DD methods, EUCAST BPs demonstrated lower susceptibility at 65% and 66%, compared to 74% and 72% (FDA) and 87% and 89% (CLSI) by HardyDisks and MASTDISCS, respectively. CA ranged from 75% to 90%, with 8 to 25% mE, 0 to 19% ME, and 0 to 20% VME and varied based on disk, GNB, and BPs evaluated. Both DD methods performed poorly for Acinetobacter baumannii complex. There is considerable variability when cefiderocol ASTs are interpreted using CLSI, FDA, and EUCAST breakpoints. DD offers a convenient alternative approach to BMD methods for cefiderocol AST, with the exception of A. baumannii complex isolates. CI - Copyright (c) 2020 American Society for Microbiology. FAU - Morris, C Paul AU - Morris CP AD - Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. AD - National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. FAU - Bergman, Yehudit AU - Bergman Y AD - Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Tekle, Tsigedera AU - Tekle T AD - Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Fissel, John A AU - Fissel JA AD - Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Tamma, Pranita D AU - Tamma PD AD - Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Simner, Patricia J AU - Simner PJ AUID- ORCID: 0000-0001-6134-151X AD - Division of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA psimner1@jhmi.edu. LA - eng PT - Journal Article DEP - 20201217 PL - United States TA - J Clin Microbiol JT - Journal of clinical microbiology JID - 7505564 RN - 0 (Anti-Bacterial Agents) RN - 0 (Cephalosporins) SB - IM CIN - https://doi.org/10.1128/JCM.00966-20 CIN - https://doi.org/10.1128/JCM.00951-20 MH - *Anti-Bacterial Agents/pharmacology MH - *Cephalosporins MH - Gram-Negative Bacteria MH - Humans MH - Microbial Sensitivity Tests MH - Cefiderocol PMC - PMC7771458 OTO - NOTNLM OT - antimicrobial susceptibility testing OT - broth microdilution OT - cefiderocol OT - disk diffusion EDAT- 2020/09/18 06:00 MHDA- 2021/06/24 06:00 PMCR- 2021/06/17 CRDT- 2020/09/17 05:38 PHST- 2020/06/26 00:00 [received] PHST- 2020/09/07 00:00 [accepted] PHST- 2020/09/18 06:00 [pubmed] PHST- 2021/06/24 06:00 [medline] PHST- 2020/09/17 05:38 [entrez] PHST- 2021/06/17 00:00 [pmc-release] AID - JCM.01649-20 [pii] AID - 01649-20 [pii] AID - 10.1128/JCM.01649-20 [doi] PST - epublish SO - J Clin Microbiol. 2020 Dec 17;59(1):e01649-20. doi: 10.1128/JCM.01649-20. Print 2020 Dec 17.