2044. Efficacy of Ceftazidime-Avibactam against Multi-Drug Resistant Enterobacteriaceae and Pseudomonas aeruginosa from the Phase 3 Clinical Trial Program
Session: Poster Abstract Session: Antimicrobial Resistant Infections: Treatment
Saturday, October 29, 2016
Room: Poster Hall
  • Phase lll MDR ID Week 2016 poster PRINT_6 Oct 2016_without crops.pdf (322.9 kB)
  • Background: Ceftazidime-avibactam (CAZ-AVI) is CAZ combined with the novel non-β-lactam β-lactamase (BL) inhibitor AVI, which inhibits extended-spectrum BLs (ESBLs), KPCs, AmpCs and some OXA enzymes. CAZ-AVI has completed Phase 3 clinical trials for treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). An assessment of patient outcome by multi-drug resistance (MDR) of key pathogens was performed.

    Methods: MDR was defined as resistance to at least 3 categories of antimicrobials. Susceptibility testing results were interpreted according to CLSI breakpoints. The favorable per-pathogen microbiological response rates for CAZ-AVI and comparators (primarily carbapenem-based therapy) were pooled across five Phase 3 clinical trials (cIAI, cUTI, and a CAZ-resistant pathogen [RP] study of patients with cIAI or cUTI) in the microbiologically modified intent-to-treat (mMITT) analysis set at the test of cure (TOC) visit for MDR Enterobacteriaceae and Pseudomonas aeruginosa.

    Results: 43.4% (876/2019) of all mMITT qualifying baseline Enterobacteriaceae and Pseudomonas aeruginosa species were MDR pathogens; 434 MDR pathogens in the CAZ-AVI arm (107 from the cIAI studies, 171 from cUTI and 156 [11 cIAI and 145 cUTI] from RP) and 442 MDR pathogens on comparator arms (125 from cIAI, 167 from cUTI, and 150 [11 cIAI and 139 cUTI] from RP). The results for the favorable per-pathogen microbiological response of MDR pathogens at TOC are shown in the table.

    MDR Pathogen

    Favorable per-pathogen response rate (%)



    Enterobacteriaceae (all)

    309/403 (76.7)

    292/423 (69.0)

     Escherichia coli

    200/256 (78.1)

    180/253 (71.1)

     Klebsiella pneumoniae

    74/94 (78.7)

    74/119 (62.2)

     Enterobacter cloacae

    12/20 (60.0)

    18/22 (81.8)

     Other Enterobacteriaceae

    23/33 (69.7)

    20/29 (69.0)

    Pseudomonas aeruginosa

    22/31 (71.0)

    15/19 (78.9)

    Conclusion: CAZ-AVI was effective in the treatment of patients with cIAI and cUTI caused by MDR pathogens.

    Gregory G. Stone, PhD1, Leanne Gasink, MD2, Paul Newell, MD3, Helen Broadhurst, MSc3, Angela Wardman, BPharm3 and Katrina Yates, PhD4, (1)AstraZeneca, Waltham, MA, (2)Formerly of AstraZeneca, Wilmington, DE, (3)AstraZeneca, Macclesfield, United Kingdom, (4)Formerly contractor to AstraZeneca, Macclesfield, United Kingdom


    G. G. Stone, AstraZeneca: Employee and Shareholder , Salary

    L. Gasink, Former AstraZeneca, Current Nabriva Therapeutics: Employee , Salary

    P. Newell, AstraZeneca: Employee and Shareholder , Salary

    H. Broadhurst, AstraZeneca: Employee and Shareholder , Salary

    A. Wardman, AstraZeneca: Employee and Shareholder , Salary

    K. Yates, AstraZeneca (former): Independent Contractor , Consulting fee

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.