1833. Clinical Outcomes of Ceftolozane/tazobactam Treatment of Piperacillin/tazobactam and Ceftazidime Non-Susceptible Pathogens from Two Phase 3 Trials and Associated In Vitro Activity
Session: Poster Abstract Session: Treatment of HAIs/Antimicrobial Resistant Infections
Saturday, October 10, 2015
Room: Poster Hall
  • 101102180_CT_PT_L2b Final from Apothecom.pdf (278.3 kB)
  • Background: The rapid increase in the number of extended spectrum beta-lactamase (ESBL) Enterobacteriaceae (ENT) infections limits empiric therapy options. Ceftolozane/tazobactam (C/T) is a novel antibacterial with activity against Gram-negative pathogens, including most ESBL ENT and drug-resistant Pseudomonas aeruginosa. Ceftolozane is intrinsically stable to classic β-lactamases (BLs), including SHV, TEM and OXA enzymes (unlike piperacillin) and the addition of tazobactam protects ceftolozane from hydrolysis by most Class A BLs and ESBLs. C/T has no activity against KPCs or metallo-BLs. The objective of this analysis is to assess the efficacy and in vitro activity of C/T against piperacillin/tazobactam (P/T) or ceftazidime (CAZ) non-susceptible (NS) ENT.

    Methods: Clinical outcomes in C/T treated patients with P/T or CAZ NS ENT from Phase 3 cIAI and cUTI trials were determined. In vitro activities of C/T, P/T and CAZ were determined against Phase 3 trial and surveillance isolates (2012) from Europe and the US. P/T and CAZ susceptibility was determined according to CLSI breakpoints (BP), FDA BP were applied for C/T.

    Results: Of 637 C/T treated patients with carbapenem-S ENT, 4.9% were NS to both P/T and CAZ; 6.3% were P/T NS and 13% were CAZ NS.  Clinical cure rates for C/T ranged from 90 to 92% in P/T or CAZ NS ENT (vs 90% C/T cure rate for all ENT); in vitro activity was lowest against strains that were both P/T and CAZ NS (Table).

    Conclusion: Clinical response was high in C/T treated patients with cIAI or cUTI caused by P/T or CAZ NS pathogens; no correlation with MIC was observed. C/T displays in vitro activity against the majority of CAZ NS ENT and a subset of P/T NS ENT. The lack of cross resistance can be due to the fact that ceftolozane is not hydrolyzed by many common plasmidic BLs and the addition of tazobactam is protective against most Class A BLs, thus P/T or CAZ resistance cannot predict C/T susceptibility.




    C/T Susceptibilityb

    Phase 3



      571/637 (90)

    692/726 (95)

    7527/7963 (95)

    P/T NSc

    36/40 (90)

    18/43 (42)

    365/724 (50)

    CAZ NSc

    77/84 (92)

    62/92 (67)

    661/1073 (62)

    P/T + CAZ NSc

    29/31 (94)

    9/34 (26)

    133/474 (28)

    a  Excludes isolates non-susceptible to imipenem or meropenem

    b  MIC ≤2 mg/L

    c CLSI M-100(S22) BPs applied

    Myra Popejoy, PharmD1, Eliana Armstrong, PhD1, Benjamin Miller, PharmD1, Jennifer Huntington, PharmD1, Patricia Bernardo, ScD1, Judith Steenbergen, PhD1, David J. Farrell, PhD2 and Ellie Hershberger, PharmD1, (1)Merck and Co., Inc., Kenilworth, NJ, (2)JMI Laboratories, Inc., North Liberty, IA


    M. Popejoy, Merck and Co., Inc.: Grant Investigator , Salary

    E. Armstrong, Merck and Co., Inc.: Consultant , Consulting fee

    B. Miller, Merck and Co., Inc.: Employee , Salary

    J. Huntington, Merck and Co, Inc.: Employee , Salary

    P. Bernardo, Merck and Co., Inc.: Employee , Salary

    J. Steenbergen, Merck and Co., Inc.: Employee , Salary

    D. J. Farrell, Merck and Co., Inc.: Research Contractor , Research support

    E. Hershberger, Merck and Co., Inc.: Consultant , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.