Program Schedule

Characteristics and Outcomes of Complicated Intra-abdominal Infections Involving Pseudomonas aeruginosa from a Phase 3 Ceftolozane/Tazobactam Study

Session: Poster Abstract Session: Antimicrobial Resistance: Novel Agents and Approaches to Gram-negative Infections
Thursday, October 9, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
  • IDWeek 2014 Miller cIAI Pseudomonas (1Oct14).pdf (716.6 kB)
  • Background: Ceftolozane/tazobactam (C/T) is a novel antimicrobial with activity against pathogens causing complicated intra-abdominal infections (cIAIs), including extended-spectrum β-lactamase (ESBL)‒producing Enterobacteriaceae and drug-resistant P. aeruginosa.  The efficacy and safety of C/T + metronidazole (MTZ) compared with meropenem (MEM) were evaluated in a randomized, double-blind phase 3 trial in hospitalized patients with cIAI.  This analysis provides information on cIAI involving P. aeruginosa, a pathogen poorly described in cIAI.

    Methods: Hospitalized patients with cIAI were randomized to 4-14 days of intravenous (IV) C/T (1.5 g) + MTZ (500 mg) every 8 hours or IV MEM (1 g every 8 hours). Baseline intra-abdominal cultures were obtained.  The primary efficacy endpoint was the clinical response at the test-of-cure (TOC) visit 26-30 days after the start of study therapy.

    Results: In the microbiological intent-to-treat (MITT) population (N=806), P. aeruginosa was isolated in 72 (8.9%) patients (38 C/T + MTZ, 34 MEM); the incidence of P. aeruginosa in North America was 18%.  P. aeruginosa was more frequently associated with polymicrobial infection (94% vs 65%).  The highest incidence of P. aeruginosa occurred in patients with infections arising from the colon (14%) or appendix (11%).  P. aeruginosa infections were less likely to be hospital-acquired (2.8% vs 7.1%) but occurred more commonly in those receiving prior antibiotic therapy (65% vs 57%).  C/T and MEM were highly active in vitro against P. aeruginosa, with a minimum inhibitory concentration against 90% of pathogens (MIC90) of 2 µg/mL and 4 µg/mL, respectively.  Clinical cure rates in the microbiologically evaluable patients with P. aeruginosa were 100% (25/25) and 96% (27/28) for C/T + MTZ and MEM, respectively.

    Conclusion: In this phase 3 study in hospitalized patients with cIAI, P. aeruginosa was isolated in 8.9% of MITT patients.  Interestingly, P. aeruginosa was most commonly isolated in community-acquired infections of the colon and appendix.  Prior use of MTZ and 3rd generation cephalosporins may have predisposed patients to infection with P. aeruginosa.  Overall, patients with P. aeruginosa responded well to therapies in this study, as demonstrated by the high clinical cure rates.

    Benjamin Miller, PharmD1, Myra Popejoy, PharmD1, Ellie Hershberger, PharmD1, Judith Steenbergen, PhD1, Bhavin Busa, MS1, Guojun Yuan, PhD1, Robert Mensah, PhD1, Ian Friedland, MD1 and John Alverdy, MD, FACS2, (1)Cubist Pharmaceuticals, Lexington, MA, (2)University of Chicago, Chicago, IL


    B. Miller, Cubist Pharmaceuticals: Employee and Shareholder, Salary

    M. Popejoy, Cubist Pharmaceuticals: Employee, Salary

    E. Hershberger, Cubist Pharmaceuticals: Employee, Salary

    J. Steenbergen, Cubist Pharmaceuticals: Employee and Shareholder, Salary

    B. Busa, Cubist Pharmaceuticals: Employee, Salary

    G. Yuan, Cubist Pharmaceuticals: Employee, Salary

    R. Mensah, Cubist Pharmaceuticals: Employee and Shareholder, Salary

    I. Friedland, Cubist Pharmaceuticals: Employee and Shareholder, Salary

    J. Alverdy, Cubist Pharmaceuticals: Consultant, Consulting fee

    Findings in the abstracts are embargoed until 12:01 a.m. EDT, Oct. 8th with the exception of research findings presented at the IDWeek press conferences.

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