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

• Published in: International journal of antimicrobial agents 2019-04, Vol.53 (4), p.456-466
• Main Authors: Karlowsky, James A., Hackel, Meredith A., Tsuji, Masakatsu, Yamano, Yoshinori, Echols, Roger, Sahm, Daniel F.
• Format: Article
• Language: English
• Subjects: Acinetobacter - drug effects; Anti-Bacterial Agents - pharmacology; Burkholderia cepacia - drug effects; Cefiderocol; Cephalosporins - pharmacology; Drug Resistance, Multiple, Bacterial; Europe; global; Gram-negative bacilli; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - isolation & purification; Gram-Negative Bacterial Infections - drug therapy; Gram-Negative Bacterial Infections - microbiology; Humans; in vitro; Microbial Sensitivity Tests; North America; Pseudomonas aeruginosa - drug effects; siderophore; Siderophores - pharmacology; Stenotrophomonas maltophilia - drug effects; surveillance
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2018.11.007

•Cefiderocol is an investigational parenteral siderophore cephalosporin•Cefiderocol MICs were ≤4 µg/mL for 99.4% of 8954 isolates of Gram-negative bacilli•99.6% of meropenem-non-susceptible Enterobacteriaceae had cefiderocol MICs ≤4 µg/mL•99.7% of meropenem-non-susceptible P. aeruginosa had cefiderocol MICs ≤4 µg/mL•96.1% of meropenem-non-susceptible Acinetobacter spp. had cefiderocol MICs ≤4 µg/mL 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.