165 - Cefiderocol Treatment for Serious Infections Caused by Carbapenem-resistant Bacteria: Post-hoc Analysis of Outcomes by Pathogen in the CREDIBLE-CR Study

Background: The efficacy and safety of cefiderocol (CFDC), a novel siderophore cephalosporin, for the treatment of serious infections due to carbapenem-resistant (CR) Gram-negative pathogens was assessed in the CREDIBLE-CR study. The current analysis evaluated clinical and microbiological outcomes by baseline CR pathogen.

Methods: An open-label, prospective, randomised 2:1, Phase 3 study (CREDIBLE-CR; NCT02714595) was conducted in adult patients with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, bloodstream infections or sepsis, and complicated urinary tract infections caused by CR Gram-negative pathogens. Patients received either intravenous (IV) CFDC 2g, q8h, 3-h infusion, or IV best available therapy (BAT: up to 3 drugs in combination), for 7–14 days (extendable to 21 days). Clinical and microbiological outcomes were assessed in the CR microbiological intent-to-treat (CR-MITT) population by CR pathogen, baseline MIC and by mechanism of carbapenem resistance at test of cure (TOC). Only summary statistics were collected.

Results: In the CR-MITT population (CFDC N=80; BAT N=38), Acinetobacter baumannii (46.3% and 44.7%), Klebsiella pneumoniae (33.8% and 31.5%), and Pseudomonas aeruginosa (15% and 26%) were the most frequent pathogens in CFDC and BAT arms, respectively. For all CR pathogens, clinical cure rates were achieved in 52.5% in the CFDC arm and 50.0% in the BAT arm at TOC; rates were similar between treatment arms by baseline CR pathogen (Table 1). Numerically higher clinical cure and microbiological outcomes were observed with CFDC for Enterobacterales (Table 1), especially against NDM-producing bacteria or those with porin-channel mutations (Table 1). CFDC MIC values ranged between ≤0.03 and 4 μg/mL, except for one pathogen (Table 2). Microbiological outcomes for CR A. baumannii, CR K. pneumoniae, and CR P. aeruginosa at TOC by baseline MICs of ≤4 μg/mL ranged between 0–40%, 0–100%, and 0–100%, respectively; at MIC ≤4 μg/mL, clinical and microbiological outcomes were equal (Table 2).Table 1. Clinical and microbiological outcomes by most frequent baseline CR pathogens and CR mechanisms at test of cure (all infection sites) in the carbapenem-resistant microbiological intent-to-treat* population.
Table 2. Clinical cure and microbiological eradication rates by CR pathogen in the CR-Micro-ITT population in CFDC arm


Conclusion: CFDC, via a novel mechanism of entry and its stability against β-lactamases, was effective against serious infections caused by CR pathogens with various resistance mechanisms or baseline MIC values.

Presenting Author(s)

• 

  Yuko Matsunaga, MD

  Medical Director
  Shionogi Inc.
  Florham Park, NJ

  Disclosure: Shionogi Inc. (Employee)

  Slides Slides and Audio

Co-Author(s)

• MA

  Mari Ariyasu, BPharm

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

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

  Kiichiro Toyoizumi, PhD

  Principal Biostatistician
  Shionogi Inc
  Florham Park, New Jersey

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

  Masahiro Kinoshita, MPharm

  Global MA Coordinator for ID area​
  Shionogi & Co., Ltd.
  Osaka, Osaka, Japan

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

  Roger Echols, MD

  Consultant
  Infectious Disease Drug Development Consulting LLC
  Easton, Connecticut

  Disclosure: Shionogi Inc. (Consultant)
• TN

  Tsutae Den Nagata, MD

  Senior Vice President
  Shionogi & Co., Ltd.
  Osaka, Osaka, Japan

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