Clinical Response of Cefiderocol Compared with Imipenem/Cilastatin in the Treatment of Adults with Complicated Urinary Tract Infections with or without Pyelonephritis or Acute Uncomplicated Pyelonephritis: Results from a Multicenter, Double-blind, Randomized Study (APEKS-cUTI). (4th October 2017)

• Record Type: Journal Article
• Authors: Portsmouth, Simon; Van Veenhuyzen, David; Echols, Roger; Machida, Mitsuaki; Ferreira, Juan Camilo Arjona; Ariyasu, Mari; Nagata, Tsutae Den
• Is Part Of: Open forum infectious diseases. Volume 4(2017)Supplement 1
• Page Start: S537
• Page End: S538
• Publication Date: 2017-10-04
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofx163.1399
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: 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. Methods: 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. Results: 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. Conclusion: 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. Disclosures: 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