Successful shortening of tuberculosis treatment using adjuvant host-directed therapy with FDA-approved phosphodiesterase inhibitors in the mouse model.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Antitubercular Agents/*therapeutic use ; Phosphodiesterase Inhibitors/*therapeutic use ; Tuberculosis/*therapy; Animals ; Cilostazol ; Disease Models, Animal ; Mice ; Piperazines/therapeutic use ; Purines/therapeutic use ; Sildenafil Citrate ; Sulfones/therapeutic use ; Tetrazoles/therapeutic use ; Time Factors ; Treatment Outcome ; United States ; United States Food and Drug Administration
    • Abstract:
      Global control of tuberculosis (TB), an infectious disease that claims nearly 2 million lives annually, is hindered by the long duration of chemotherapy required for curative treatment. Lack of adherence to this intense treatment regimen leads to poor patient outcomes, development of new or additional drug resistance, and continued spread of M.tb. within communities. Hence, shortening the duration of TB therapy could increase drug adherence and cure in TB patients. Here, we report that addition of the United Stated Food and Drug Administration-approved phosphodiesterase inhibitors (PDE-Is) cilostazol and sildenafil to the standard TB treatment regimen reduces tissue pathology, leads to faster bacterial clearance and shortens the time to lung sterilization by one month, compared to standard treatment alone, in a murine model of TB. Our data suggest that these PDE-Is could be repurposed for use as adjunctive drugs to shorten TB treatment in humans.
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    • Grant Information:
      AI30036 United States AI NIAID NIH HHS; R01 AI037856 United States AI NIAID NIH HHS; N01AI30036 United States AI NIAID NIH HHS; United States HHMI Howard Hughes Medical Institute; AI37856 United States AI NIAID NIH HHS; R01 AI036973 United States AI NIAID NIH HHS; AI36973 United States AI NIAID NIH HHS
    • Accession Number:
      0 (Antitubercular Agents)
      0 (Phosphodiesterase Inhibitors)
      0 (Piperazines)
      0 (Purines)
      0 (Sulfones)
      0 (Tetrazoles)
      BW9B0ZE037 (Sildenafil Citrate)
      N7Z035406B (Cilostazol)
    • Publication Date:
      Date Created: 20120210 Date Completed: 20120924 Latest Revision: 20211021
    • Publication Date:
      20231215
    • Accession Number:
      PMC3272040
    • Accession Number:
      10.1371/journal.pone.0030749
    • Accession Number:
      22319585