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

Background: Non-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.

Methods: 12,293 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.

Results: CFDC 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.Table. Activity of cefiderocol and comparators against non-fermenting Gram-negative bacilli


Conclusion: In 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.

Presenting Author(s)

• 

  Yuuta Ukai, MSc

  Senior Researcher
  Shionogi & Co., Ltd.
  Osaka, Osaka, Japan

  Disclosure: Shionogi & Co., Ltd.: Employee

  Slides Slides and Audio

Co-Author(s)

• RN

  Rio Nakamura, BSc

  Senior Researcher
  Shionogi & Co., Ltd.
  Osaka, Osaka, Japan

  Disclosure: Shionogi & Co., Ltd.: Employee
• MO

  Merime Oota, BSc

  Senior Researcher
  Shionogi & Co., Ltd.
  Osaka, Osaka, Japan

  Disclosure: Shionogi & Co., Ltd. (Employee)
• MH

  Meredith Hackel, PhD MPH

  Laboratory Director
  IHMA, Inc.
  Schaumburg, Illinois

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• RE

  Roger Echols, MD

  Consultant
  Infectious Disease Drug Development Consulting LLC
  Easton, Connecticut

  Disclosure: Shionogi Inc. (Consultant)
• MT

  Miki Takemura, MS

  Associate Director, Laboratory for Drug Discovery and Disease Research
  Shionogi & Co., Ltd.
  Osaka, Osaka, Japan

  Disclosure: Shionogi & Co., Ltd. (Employee)
• 

  Yoshinori Yamano, PhD

  Chief Scientific Officer for Infectious Diseases
  Shionogi & Co., Ltd.
  Osaka, Osaka, Japan

  Disclosure: Shionogi & Co., Ltd. (Employee)
• DS

  Daniel F. Sahm, PhD

  VP Global Microbiology Services & Chief Scientific Officer
  IHMA, Inc.
  Schaumburg, Illinois

  Disclosure: IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)