1869. 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)
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
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.

Table: Clinical Response Rate at TOC (Micro-ITT population)

CFDC

IPM/CS

adjusted difference

(95% CI)

Composite of clinical and microbiological response rate

72.6%
(183/252)

54.6%
(65/119)

28.92%
(8.23, 28.92)

Clinical response rate per patient

89.7 % (226/252 )

87.4 % (104/119 )

2.39%
(-4.66, 9.44)

Clinical response rate per uropathogen

Monomicrobial

Escherichia coli

131/146 (89.7%)

68/77 (88.3%)

Klebsiella pneumoniae

41/46 (89.1%)

21/25 (84.0%)

Proteus mirabilis

13/13 (100.0 %)

1/1 (100.0%)

Pseudomonas aeruginosa

11/15 (73.3 %)

3/4 (75.0 %)

Polymicrobial

10/11 (90.9 %)

3/4 (75.0 %)


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.

Simon Portsmouth, MD1, David Van Veenhuyzen, MBChB, MPharmMed2, Roger Echols, MD, FIDSA3, Mitsuaki Machida, MS4, Juan Camilo Arjona Ferreira, MD2, Mari Ariyasu, BA4 and Tsutae Den Nagata, MD, PhD, FFPM4, (1)Shionogi Inc., Florham Park, NJ, (2)SHIONOGI INC., Florham Park, NJ, (3)ID3C, Easton, CT, (4)SHIONOGI & CO., LTD., Osaka, Japan

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

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.