1836. A 2012-2014 Global Antimicrobial Surveillance of Iclaprim Against Clinical Strains Causing Hospital-Associated Bacterial Pneumonia (HABP) and Skin and Skin Structure Infections (SSSI)
Session: Poster Abstract Session: Antibacterial Susceptibility Surveillance
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Poster 1836-final.pdf (443.8 kB)
  • Background: ICL, a new generation diaminopyrimidine compound, is a dihydrofolate reductase inhibitor antibiotic in Phase 3 clinical development. An in vitro retrospective surveillance study on the antimicrobial spectrum and activity of iclaprim was performed against clinical isolates causing HABP and SSSI. Methods: 1636 clinical Gram-positive isolates causing HABP (601) and SSSI (577) were collected from the US, Europe, Latin America, and Asia Pacific during 2012-2014. Reference broth microdilution tests were conducted according to the Clinical and Laboratory Standards Institute (CLSI M07-A10, 2015) methods. Quality control (QC) ranges and interpretive criteria for comparator compounds were as published in (CLSI M100-S25, 2015). QC ranges for iclaprim were those approved by CLSI and published in M100-S25. Results: The MIC distributions of iclaprim, trimethoprim, trimethoprim-sulfamethoxazole and comparator antimicrobials for all S. aureus, including methicillin-resistant (MRSA) and -susceptible (MSSA) strains, beta-hemolytic streptococci, and S. pneumoniae are shown in the Table.
    Antimicrobials (MIC50/90; mg/L)
    Pathogen n ICL VAN LIN DAP TMP TMP/SMX
    S.aureus 1,178 0.06/0.12 1/1 1/1 0.25/0.5 1/2 0.06/0.12
    MRSA 582 0.06/0.12 1/1 1/1 0.25/0.5 1/8 0.06/0.25
    MSSA 596 0.06/0.12 1/1 1/1 0.25/0.5 1/2 0.06/0.06
    Beta-hemolytic streptococci 199 0.06/0.25 0.25/0.5 1/1 0.12/0.25 1/2 0.12/0.25
    S. pneumoniae 259 0.06/0.2 0.25/0.5 1/1 0.12/0.25 2/64 0.25/8
    Total 1636

    Globally, ICL MIC50/90s for S. aureus including MRSA were l6-fold lower than those for TMP and similar to TMP/SMX. ICL MIC 50/90s for beta-hemolytic streptococci were 8-fold lower than for TMP and 2-fold lower than for TMP/SMX. ICL 50/90 were 32-fold lower than TMP and 4-fold lower than TMP/SMX for S. pneumoniae. ICL MIC 50/90 were 0.06/0.12, 0.06/0.25, and 0.06/2 for US S. aureus, beta-hemolytic Streptococcus, and S. pneumoniae, respectively; corresponding values for European isolates were 0.6/0.12, 0.12/0.25, and 0.6/4, respectively.

    Conclusion: ICL was potently active against all S. aureus, beta-hemolytic streptococcus, and S. pneumoniae clinical SSSI and HABP isolates globally from 2012-2014. ICL could be an important new therapeutic option for the treatment of SSSI and HABP, especially cases caused by multidrug resistant Gram-positive bacteria. Pivotal clinical trials are warranted to evaluate ICL for the indications of SSSI and HABP.

    David Huang, MD, PhD1, Thomas M. File Jr., MD, MSc, MACP, FIDSA, FCCP2, Mark Wilcox, MD3, Matthew Dryden, MD4, G Corey, MD5 and Rajesh Shukla, PhD1, (1)Motif BioSciences, New York, NY, (2)Division of Infectious Diseases, Summa Health System, Akron, OH, (3)University of Leeds, Leeds, United Kingdom, (4)Royal Hampshire County Hospital, Winchester, United Kingdom, (5)Duke Univ. Med. Ctr., Durham, NC

    Disclosures:

    D. Huang, Motif BioSciences: Employee , Salary

    T. M. File Jr., Motif BioSciences: Scientific Advisor , Consulting fee

    M. Wilcox, MERCK: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    PFIZER: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    SUMMIT: Grant Investigator and Scientific Advisor , Consulting fee and Research support
    SERES: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    DA VOLTERRA: Grant Investigator and Scientific Advisor , Consulting fee and Research support
    BIOMERIEUX: Investigator and Scientific Advisor , Consulting fee and Research support
    ALERE: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    ACTELION: Grant Investigator and Scientific Advisor , Consulting fee and Research support

    M. Dryden, Motif BioSciences: Scientific Advisor , Consulting fee

    G. Corey, None

    R. Shukla, Motif BioSciences: Employee , Salary

    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.