692. In Vitro Antibacterial Activity of Cefiderocol Against a Multi-national Collection of Carbapenem-Nonsusceptible Gram-Negative Bacteria From Respiratory Infections: SIDERO-WT-2014–2017

Abstract

BackgroundCefiderocol (CFDC) is a new siderophore cephalosporin with potent in vitro activity against a broad range of Gram-negative (GN) pathogens, including carbapenem-nonsusceptible (Carb-NS) strains. We evaluated the in vitro activity of CFDC and comparator agents against recent clinical Carb-NS GN respiratory isolates collected from North America and Europe as part of the multi-national SIDERO-WT surveillance program.MethodsA total of 2831 Carb-NS GN respiratory isolates collected from 2014 to 2017 were tested centrally (IHMA, Inc., Schaumburg, IL). Minimum inhibitory concentrations (MIC) were determined for CFDC, cefepime (FEP), ceftazidime–avibactam (CZA), ceftolozane-tazobactam (C/T), ciprofloxacin (CIP), colistin (CST), and meropenem (MEM) by broth microdilution and interpreted according to the 2018 CLSI guidelines. CFDC MICs were tested in iron-depleted cation-adjusted Mueller–Hinton broth, and interpreted according to the 2018 CLSI provisional breakpoints. Carb-NS strains were defined as MEM MIC of ≥2 µg/mL for Enterobacteriaceae (ENB) and of ≥4 µg/mL for nonfermenters (NF).ResultsCFDC exhibited predictable in vitro activity against 2807 clinically relevant Carb-NS GN isolates (214 ENB, 1086 A. baumannii complex, 693 P. aeruginosa, 794 S. maltophilia, and 20 Burkholderia cepacia) isolated from respiratory infections. CFDC was the most active agent against Carb-NS ENB with 97.7% susceptibility followed by 78.0% CZA, 59.4% CST, and 16.4% CIP. Against Carb-NS A. baumannii complex, CFDC demonstrated 94% susceptibility vs. 83.7% for CST. CFDC was the most active agent against Carb-NS P. aeruginosa with 99.9% susceptibility followed by 97.8% CST, 77.6% C/T, and 77.5% CZA. 99.7% of S. maltophilia and 100% of B. cepacia isolates had CFDC MICs of ≤4 µg/mL. The MIC90s of tested compounds for clinically relevant pathogens are shown in the table.ConclusionIn a multinational collection of Carb-NS GN respiratory isolates, CFDC demonstrated potent in vitro activity with MIC90 of ≤4 µg/mL for all clinically relevant ENB and NF. These findings suggest that CFDC can be a potential option for the treatment of respiratory infections caused by Carb-NS ENB, A. baumannii complex, P. aeruginosa, S. maltophilia, and B. cepacia. Disclosures All authors: No reported disclosures.