In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem-non-susceptible Gram-negative bacilli, including serine carbapenemase- and metallo-β-lactamase-producing isolates (SIDERO-WT-2014 Study)

Cefiderocol is a siderophore cephalosporin in development for treatment of infections caused by Gram-negative bacilli, including carbapenem-resistant and multidrug-resistant isolates. beta-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 mu g/mL against 97.7% of tested isolates, including 100% of IMP-positive (range, 1-2 mu g/mL), OXA-58-positive (MIC90, 1 mu g/mL), KPC-positive (MIC90, 2 mu g/mL), VIM-positive (MIC90, 2 mu g/mL), and OXA-48-like-positive (MIC90, 4 mu g/mL) isolates; 99.3% of carbapenemase-negative isolates (MIC90, 1 mu g/mL); 97.2% of OXA-23-positive isolates (MIC90, 1 mu g/mL); 95.2% of OXA-24-positive isolates (MIC90, 1 mu g/mL); 91.7% of GES-positive isolates (MIC90, 4 mu g/mL); and 64.3% of NDM-positive isolates (MIC90, 8 mu g/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 mu g/mL, confirming there was no clear correlation between carriage of beta-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 mu g/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 mu g/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-beta-lactamase producing isolates identified. (c) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)