In Vitro Activity of Cefiderocol, a Siderophore Cephalosporin, Against Gram-Negative Bacilli Isolated by Clinical Laboratories in North America and Europe in 2015-2016: SIDERO-WT-2015

Cefiderocol (S-649266) is a parenteral siderophore cephalosporin in phase III of clinical development. In this study, we determined the in vitro susceptibility to cefiderocol and comparators of a 2015-2016 collection of 8954 clinical isolates of Gram-negative bacilli (GNB), provided by 100 clinical laboratories in North America and Europe, using the Clinical and Laboratory Standards Institute broth microdilution method. Iron-depleted cation-adjusted Mueller-Hinton broth was used to test cefiderocol. The concentration of cefiderocol inhibiting 90% of isolates (MIC90) was 0.5 mg/L (North America; n = 2470) and 1 mg/L (Europe; n = 3,543) for Enterobacteriaceae, 0.5 mg/L (North America; n = 619) and 0.5 mg/L (Europe; n = 921) for Pseudomonas aeruginosa, 1 mg/L (North America; n = 308) and 2 mg/L (Europe; n = 664) for Acinetobacter spp., 0.5 mg/L (North America; n = 165) and 0.25 mg/L (Europe; n = 175) for Stenotrophomonas maltophilia, and 0.12 mg/L (North America; n = 40) and 0.5 mg/L (Europe; n = 49) for Burkholderia cepacia complex spp. Cefiderocol MICs were <= 4 mg/L for 99.9% (6005/6013) of Enterobacteriaceae, 99.9% (1539/1540) of P. aeruginosa, 96.4% (937/972) of Acinetobacter spp., 99.4% (338/340) of S. maltophilia, and 94.4% (84/89) of Burkholderia cepacia complex spp. isolates tested. Against meropenem-non-susceptible isolates, MICs to cefiderocol were <= 4 mg/L for 99.6% (245/246) of Enterobacteriaceae, 99.7% (394/395) of P. aeruginosa, 96.1% (540/562) of Acinetobacter spp., and 87.1% (27/31) of B. cepacia complex spp. We conclude that cefiderocol demonstrated potent in vitro activity (MIC <= 4 mg/L) against the majority (99.4%, 8903/8954) of clinical isolates of GNB in a recent (2015-2016), multi-continent collection, including carbapenem-non-susceptible isolates. (C) 2018 The Authors. Published by Elsevier B.V.