782. Activity of Gallium (III) Compounds Against Biofilms of Multidrug-Resistant Isolates of Acinetobacter baumanni
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
Posters
  • DChang Gallium IDSA 2015 Poster FINAL.pdf (243.5 kB)
  • Background: Acinetobacter baumannii is a clinically challenging pathogen due to the emergence of multidrug resistance and ability to form biofilms. Iron (III) is critical to both physiology and virulence which has promoted interests in the development and use of agents to target iron metabolism. Gallium (III) is an iron (III) mimetic with antimicrobial activity against multiple bacterial pathogens including A. baumannii. To date studies evaluating the activity of gallium against A. baumannii have focused on planktonic but not the biofilm phenotype. To address this gap, we evaluated in vitro the activity of gallium compounds, gallium nitrate (GaNO3) and gallium meso-/protoporphyrin (GaMP/GaPP), against biofilms of clinical isolates of A. baumannii.

    Methods: Bacterial isolates used in this study included a collection from the Trauma Infectious Disease Outcome Study (n=12) and a reference strain of A. baumannii (ATCC 17978). Antimicrobial activity of gallium compounds against planktonic and biofilm bacteria was evaluated by performing broth microdilution assays in iron-limited medias, RPMI 1640 and 10% MHB-II. Microdilution assays consisted of exposing bacteria or formed 24 hour biofilms overnight to increasing concentrations (0.25-512 µM) of the gallium compounds in 96-well plates or individual wells of the Calgary Device. Concentrations reducing viability of planktonic and biofilm bacteria to 50% and 90% of the untreated control were reported as the minimum inhibitory concentration or biofilm eradication concentration 50 and 90 (MIC/MBEC50 and MIC/MBEC90) respectively.

    Results: Median IC50 and IC90 for GaNO3 were 64µM/128µM in MHBII and 128µM/256µM in RPMI, whereas IC50 and IC90 for GaMP and GaPP were 1µM/2µM and 2µM/8µM respectively with no observable difference seen with different media. The MBEC50 and MBEC90 for GaNO3, GaMP, and GaPP were 256µM/512µM, 16µM/32µM, and 128µM/256µM respectively.

    Conclusion: Gallium (III) compounds have differential activity against MDR A. baumannii in planktonic and biofilm forms. The heme-conjugated gallium compounds (GaMP/GaPP) had the most potent in vitro activity.  Further investigations should explore their potential role as novel anti-biofilm agents.

    David Chang, MD1, Rebecca Garcia, BA2, Kevin S. Akers, MD, FIDSA1,2, Joseph Wenke, PhD2 and Carlos Sanchez Jr., PhD2, (1)San Antonio Military Medical Center, Fort Sam Houston, TX, (2)Extremity Trauma and Regenerative Medicine, US Army Institute of Surgical Research, Fort Sam Houston, TX

    Disclosures:

    D. Chang, None

    R. Garcia, None

    K. S. Akers, None

    J. Wenke, None

    C. Sanchez Jr., None

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