164. in Vitro Antibacterial Activity of Cefiderocol Against Non-fermenter Clinical Strains Collected in North America and Europe from Multinational Surveillance Studies SIDERO-WT-2014–2018

Abstract

BackgroundNon-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas aeruginosa, Acinetobacter baumannii-complex (ABC), Stenotrophomonas maltophilia, and Burkholderia cepacia-complex (BCC), are recognized as difficult-to-treat organisms due to acquired and intrinsic antimicrobial resistance. This study evaluated the in vitro activity of cefiderocol (CFDC), a novel parenteral siderophore cephalosporin, and comparator agents against NFGNB clinical isolates collected in 2014–2018 as part of the multinational SIDERO-WT surveillance program.Methods12,293 non-fermenter clinical isolates, including 5310 from North America and 6983 from Europe, were tested for antimicrobial susceptibility. Minimum inhibitory concentrations (MICs) were determined for CFDC, cefepime (FEP), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), meropenem-vaborbactam (MVB), meropenem (MEM), ciprofloxacin (CIP), colistin (CST), and trimethoprim-sulfamethoxazole (SXT) by broth microdilution according to Clinical Laboratory and Standards Institute (CLSI) guidelines. MICs for aztreonam-avibactam (ATM/AVI; ATM in the presence of 4 μg/mL AVI), MVB, and SXT were determined only for SIDERO-WT 2018 strains. As per CLSI guidelines, CFDC was tested in iron-depleted media, and carbapenem-non-susceptible (CarbNS) isolates were defined as non-susceptible to MEM.ResultsCFDC demonstrated in vitro activity with MIC90s of 0.25–2 µg/mL against clinical isolates of P. aeruginosa, ABC, S. maltophilia, and BCC, including CarbNS subsets. MIC90s of CFDC against CarbNS P. aeruginosa (N=1416), CarbNS ABC (N=2274), S. maltophilia (N=1565), and CarbNS BCC (N=80) were 1, 2, 0.5, and 2 μg/mL, respectively, which were the lowest among the tested compounds (Table). The MIC90 differences between all isolates and CarbNS subsets were ≤2-fold for P. aeruginosa and ABC, showing that CFDC is active against CarbNS subsets as well as carbapenem-susceptible isolates. However, an 8-fold MIC90 difference between all isolates and CarbNS subsets was observed for BCC.ConclusionIn 4 years of consecutive multinational surveillance studies, CFDC was the most active agent among antimicrobials tested against a wide range of NFGNB, including CarbNS strains. DisclosuresYuuta Ukai, MSc, Shionogi & Co., Ltd. (Employee) Rio Nakamura, BSc, Shionogi & Co., Ltd. (Employee) Merime Oota, BSc, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)