Successful shortening of tuberculosis treatment using adjuvant host-directed therapy with FDA-approved phosphodiesterase inhibitors in the mouse model.
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.
Center for Tuberculosis Research, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Mamoudou
M
Maiga
Nisheeth
N
Agarwal
Nicole C
NC
Ammerman
Radhika
R
Gupta
Haidan
H
Guo
Marama C
MC
Maiga
Shichun
S
Lun
William R
WR
Bishai
D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use*; D000077407:Cilostazol; D004195:Disease Models, Animal; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use; D013777:Tetrazoles / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000628:therapy*; D014481:United States; D014486:United States Food and Drug Administration
D000995:Antitubercular Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D013777:Tetrazoles; D000068677:Sildenafil Citrate; D000077407:Cilostazol