• Krystyna M Kazmierczak, Masakatsu Tsuji, Mark G Wise, Meredith Hackel, Yoshinori Yamano, Roger Echols, and Daniel F Sahm.
• International Health Management Associates, Inc., Schaumburg, IL, US. Electronic address: kkazmierczak@ihmainc.com.
• Int. J. Antimicrob. Agents. 2019 Feb 1; 53 (2): 177-184.

AbstractCefiderocol is a siderophore cephalosporin in development for treatment of infections caused by Gram-negative bacilli, including carbapenem-resistant and multidrug-resistant isolates. β-Lactamase carriage and in vitro activity of cefiderocol were determined against 1272 meropenem-non-susceptible isolates of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii collected as part of the SIDERO-WT-2014 surveillance study. Minimum inhibitory concentration (MIC) values for cefiderocol were ≤4 µg/mL against 97.7% of tested isolates, including 100% of IMP-positive (range, 1-2 µg/mL), OXA-58-positive (MIC90, 1 µg/mL), KPC-positive (MIC90, 2 µg/mL), VIM-positive (MIC90, 2 µg/mL), and OXA-48-like-positive (MIC90, 4 µg/mL) isolates; 99.3% of carbapenemase-negative isolates (MIC90, 1 µg/mL); 97.2% of OXA-23-positive isolates (MIC90, 1 µg/mL); 95.2% of OXA-24-positive isolates (MIC90, 1 µg/mL); 91.7% of GES-positive isolates (MIC90, 4 µg/mL); and 64.3% of NDM-positive isolates (MIC90, 8 µg/mL). A total of 29 isolates (2.3%; 15 OXA-23-producers, 6 OXA-24-producers, 5 NDM-producers, and 3 carbapenemase-negative isolates) exhibited cefiderocol MIC ≥8 µg/mL, confirming there was no clear correlation between carriage of β-lactamases included in the molecular testing algorithm and elevated cefiderocol MICs. Similarly, no correlation was observed between cefiderocol MICs and truncation or loss of porin proteins in meropenem-non-susceptible isolates of E. coli and K. pneumoniae. Cefiderocol MICs were also ≤4 µg/mL against 99.3% of 136 colistin-resistant Enterobacteriaceae collected as part of the SIDERO-WT-2014 study, including isolates carrying mcr-1 (MIC90, 2 µg/mL). Cefiderocol demonstrated potent in vitro activity against a collection of carbapenemase-producing and carbapenemase-negative meropenem-non-susceptible Gram-negative bacilli for which few treatment options are available, including the majority of metallo-β-lactamase producing isolates identified.Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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