Researchers at Johns Hopkins Children’s Center have run a preliminary study testing “four new regimens that have the potential to treat and save the lives of people with multidrug-resistant (MDR) tuberculous (TB) meningitis.” Hopkins Medicine has the release.
Study investigators state that these new regimens could be “used to treat people with MDR-TB meningitis on a case-by-case basis now.” As of now, there are no FDA-approved antibiotic treatments specifically effective for tuberculous meningitis, and previous studies showed that “the FDA-approved regimen of three antibiotics currently used for treating drug-resistant pulmonary TB…is not effective in treating TB meningitis.”
Researchers first “created a chemically identical and scan-friendly version of the antibiotic pretomanid, and conducted a whole-body study in eight people: six healthy volunteers and two patients newly diagnosed with pulmonary TB. Using PET and CT imaging, researchers measured the antibiotic’s penetration into the brain and lung tissue, and found that pretomanid penetrated the brain more than two times better than the lungs of all human subjects.”
Next, researchers tested four different antibiotics and “their penetration into the lung and brain tissues in mouse and rabbit models of TB meningitis.” All four “distributed well in the body, but with significantly different brain and lung tissue penetration.” Sanjay Jain, M.D., senior author of the new study, said that this “preferential accumulation of different antibiotics in brain or lung tissues is very important, and explains why certain antibiotics are highly effective in the lungs, but not in the brain and vice versa.”
Mathematical simulations showed that, of the four antibiotics, only “pretomanid achieved therapeutic brain tissue exposures at the standard human oral dosing.” Three pretomanid-based multidrug regimens “were highly effective in treating TB meningitis in animal models when administered at human equivalent dosing.”
