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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Adjuvant host-directed therapy with types 3 and 5 but not type 4 phosphodiesterase inhibitors shortens the duration of tuberculosis treatment
Journal of Infectious Diseases, Volume 208, No. 3, Year 2013
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Description
Background. Shortening tuberculosis treatment could significantly improve patient adherence and decrease the development of drug resistance. Phosphodiesterase inhibitors (PDE-Is) have been shown to be beneficial in animal models of tuberculosis. We assessed the impact of PDE-Is on the duration of treatment in tuberculous mice.Methods. We analyzed the time to death in Mycobacterium tuberculosis-infected mice receiving type 4 PDE-Is (rolipram and cilomilast) and the impact on bacterial burden, time to clearance, and relapse when types 3 and 5 PDE-Is (cilostazol and sildenafil, respectively) and rolipram were added to the standard treatment. We investigated pharmacokinetic interactions between PDE-Is (cilostazol and sildenafil) and rifampin.Results. The type 4 PDE-Is rolipram and cilomilast accelerated the time to death in tuberculous mice. The addition of rolipram to standard tuberculosis treatment increased bacterial burden and did not decrease the time to bacterial clearance in the lung, while the addition of the cilostazol and sildenafil reduced the time to clearance by 1 month. Cilostazol and sildenafil did not have negative pharmacokinetic interactions with rifampin.Conclusions. Type 4 PDE-Is may increase the severity of tuberculosis and should be carefully investigated for use in patients with latent or active tuberculosis. Cilostazol and sildenafil may benefit tuberculosis patients by shortening the duration of therapy. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3699007/bin/supp_208_3_512__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3699007/bin/supp_jit187_jit187supp.doc
Authors & Co-Authors
Maiga, Mamoudou
United States, Baltimore
Johns Hopkins School of Medicine
Mali, Bamako
Université Des Sciences
Ammerman, Nicole C.
United States, Baltimore
Johns Hopkins School of Medicine
South Africa, Durban
Africa Health Research Institute
Maiga, Mariama C.
United States, Baltimore
Johns Hopkins School of Medicine
Tounkara, Anatole
Mali, Bamako
Université Des Sciences
Siddiqui, Sophia
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Polis, Michael A.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Murphy, Robert L.
United States, Evanston
Northwestern University
Bishai, William R.
United States, Baltimore
Johns Hopkins School of Medicine
United States, Chevy Chase
Howard Hughes Medical Institute
South Africa, Durban
Africa Health Research Institute
Statistics
Citations: 46
Authors: 8
Affiliations: 6
Identifiers
Doi:
10.1093/infdis/jit187
ISSN:
00221899
Research Areas
Health System And Policy