The PET scan data revealed that the amount of 11C-rifampin uptake was lowest in the walls of the TB-caused lung lesions and cavities, less than half what was seen in uninfected lung tissues.

“This is eye-opening since the lesions and cavities are the sites known to have the largest populations of bacteria in TB patients,” Ordonez says. “Therefore, rifampin is not getting where we need it most.”


The researchers used the findings on drug concentrations at the infection sites to predict how increasing the rifampin dose might shorten the treatment time for TB patients. This work — done in collaboration with teams at the University of Maryland School of Pharmacy, led by Vijay Ivaturi, Ph.D., and the Texas Tech University Health Sciences Center, led by Tawanda Gumbo, M.D. — suggests that increasing the dose of rifampin to higher, yet safely tolerated levels could reduce the treatment course in most TB patients from six months to four months.

“This would have a dramatic impact on the worldwide fight against TB,” Jain says.

The researchers say that further human trials are needed to validate the promising results of this study, and perhaps, broaden the use of the PET-CT technique beyond anti-TB drugs. For example, similar studies are being conducted with patients who have infections due to methicillin-resistant Staphylococcus aureus, or MRSA, which often is treated with a long-term course of rifampin.

“We hope that the tool will one day enable clinicians to determine the most effective doses of specific drugs in specific patients, so as to further optimize the treatment of infectious diseases,” Jain says.

Along with Jain and Ordonez, the other members of the research team from the Johns Hopkins University School of Medicine are Camilo Ruiz-Bedoya, M.D.; Allen Chen, Ph.D.; Elizabeth Tucker, M.D.; Michael Urbanowski, Ph.D.; Lisa Pieterse; Martin Lodge, Ph.D.; Maunank Shah, M.D., Ph.D.; Daniel Holt; William Mathews, Ph.D.; Robert Dannals, Ph.D.; and Steven Rowe, M.D., Ph.D.

Team members from other organizations are Hechuan Wang, Ph.D. (now at AstraZeneca), Jogarao Gobburu, Ph.D., M.B.A., and Vijay Ivaturi, Ph.D., of the University of Maryland School of Pharmacy (Baltimore, Maryland); Gesham Magombedze, Ph.D., Shashikant Srivastava, Ph.D., and Tawanda Gumbo, M.D., of the Texas Tech University Health Sciences Center (Dallas, Texas); E. Fabian Cardozo, of the Fred Hutchinson Cancer Research Center (Seattle, Washington); and Charles Peloquin, Pharm.D., of the University of Florida School of Pharmacy (Gainesville, Florida).

Funding for the study was provided by grants from the National Heart, Lung and Blood Institute (R01-HL131829), the National Institute of Allergy and Infectious Diseases (R56-AI145435) and the National Institutes of Health Director’s Transformative Research Award (R01-EB020539).

No conflicts of interest related to the study were reported.

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