220. Extended-Spectrum Beta-Lactamase Infections and Clinical Response in Tigecycline Clinical Trials
Session: Poster Abstract Session: Antimicrobial Resistance: Clinical Studies
Friday, October 21, 2011
Room: Poster Hall B1
Handouts
  • TY10199 ESBLs - IDSA11 Final.pdf (101.4 kB)
  • Background: Tigecycline (TGC) is an expanded broad-spectrum antibiotic with in-vitro activity against gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL) organisms. It is approved in the US for the treatment of complicated skin and skin structure infection (cSSSI), complicated intra-abdominal infection (cIAI) and community-acquired pneumonia (CAP). In addition to the approved indications, TGC has been studied in clinical trials in patients with hospital-acquired pneumonia (HAP) and diabetic foot infection (DFI).The purpose of this current analysis was to compare the efficacy of TGC versus comparators (COM) in treating infections caused by ESBL-producing organisms in clinically evaluable (CE) subjects from multinational phase III-IV clinical trials.

    Methods: Hospitalized subjects enrolled in phase III-IV trials of TGC and infected with ESBL-producing organisms at baseline were identified. Clinical and microbiological characteristics of infections were summarized and clinical response by indication was analyzed.

    Results: 219 (TGC 123; COM 96) subjects with baseline ESBL infections were identified in the TGC trials, of which 162 (TGC 89; COM 73) were clinically evaluable. 92.2% of ESBL infections occurred outside of North America with India contributing 32.9%. The infections were most commonly identified in cIAI (35.6%) and in HAP (32.9%) clinical trials. More TGC subjects were prior antibiotic failures (45.5% vs. 25.0%) and had concomitant baseline bacteremia (16.3% vs. 8.3%). Clinical efficacy by indication is shown in the table below. No decrease in the rate of cure was found in organisms with increasing TGC minimum inhibitory concentrations (MICs).

     

    Infection Type

    TGC

    n/N (%)

    COM

    n/N (%)

    CAP

    1/1 (100.0)

    1/1 (100.0)

    cIAI

    22/28 (78.6)

    26/31 (83.9)

    cSSSI

    8/10 (80.0)

    5/7 (71.4)

    DFI

    4/11 (36.4)

    9/14 (64.3)

    HAP

    13/20 (65.0)

    19/20 (95.0)

    Resistant Pathogen

    13/19 (68.4)

    N/A

    Conclusion: Tigecycline demonstrated similar efficacy in two approved indications (cIAI and cSSSI) but had lower efficacy in trials that did not meet their primary endpoints (HAP, DFI).


    Subject Category: C. Clinical studies of bacterial infections and antibacterials including sexually transmitted diseases and mycobacterial infections (surveys, epidemiology, and clinical trials)

    Paul McGovern, Jean Li Yan, Alvaro Quintana and Tim Babinchak, Pfizer Inc., Collegeville, PA

    Disclosures:

    P. McGovern, Pfizer Inc.: Employee, Salary

    J. L. Yan, Pfizer Inc.: Employee, Salary

    A. Quintana, Pfizer Inc.: Employee, Salary

    T. Babinchak, Pfizer Inc.: Employee, Salary

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.