Cefiderocol (CFDC, S-649266) is a novel siderophore cephalosporin with potent activity against Gram-negative bacteria that is being developed to treat serious MDR Gram-negative infections. APEKS-cUTI was a, multicenter, double-blind, randomized trial in patients with complicated urinary tract infections (cUTI) or acute uncomplicated pyelonephritis (AUP). Patients >18 yrs with a cUTI or AUP and a positive urine culture were randomized 2:1 to intravenous CFDC (2 g) or imipenem/cilastatin (IPM/CS) (1/1 g) over 1 hour, every 8-hours for 7 to 14 days. No oral step down antibiotics were allowed. The primary endpoint was a composite of clinical and microbiological response rate at test of cure (TOC, 7 days following the end of treatment) in the Microbiological Intent to Treat (MITT) population. Clinical response at TOC in the MITT population was included in the key secondary endopoints. Of 452 randomized patients, 371 had a baseline GN uropathogen and met the Micro-ITT population definition. The composite of clinical and microbiological response rate and clinical response rates are shown in the table. CFDC was non-inferior (NI margin 15%) to IPM/CS on the primary composite endpoint response. The 95% CI excluded 0 showing superiority of CFDC vs. IPM/CS. CFDC was associated with a numerically lower incidence of AEs compared with IPM/CS. CFDC, the first siderophore antibiotic in clinical development, was superior to IPM/CS in pateints with cUTI and AUP caused by Gram-negative bacteria and was generally well tolerated. S. Portsmouth, SHIONOGI INC.: Employee, Salary; D. Van Veenhuyzen, Shionogi Inc: Employee, Salary; R. Echols, Shionogi & CO., LTD: Consultant, Consulting fee; M. Machida, Shionogi Co. Ltd.: Employee, Salary; J. C. Arjona Ferreira, SHIONOGI INC.: Employee, Salary; M. Ariyasu, SHIONOGI & CO., LTD.: Employee, Salary; T. D. Nagata, Shionogi: Employee, Salary Clinical Response Rate at TOC (Micro-ITT population)
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Portsmouth et al. (2017) studied this question.