Children’s Center researchers say they have developed four new regimens that have the potential to treat and save the lives of people with multidrug-resistant (MDR) tuberculous (TB) meningitis, based on a preliminary study with a small number of humans, rabbits and mice.

While TB meningitis — which affects the brain and spine — is extremely rare in the United States, worldwide it is believed to be the deadliest form of TB.

In a report published in Nature Communications, senior author Sanjay Jain and team present the regimens, mainly composed of antibiotics already approved by the U.S. Food and Drug Administration for other uses, or antibiotics currently in clinical trials. Study investigators say the regimens could be readily evaluated in new clinical studies, or used to treat people with MDR-TB meningitis on a case-by-case basis now.

According to the World Health Organization, tuberculosis remains a global public health threat, with the largest number of cases occurring in the Southeast Asian region and Africa, and is a leading killer by a single infectious agent, the tubercle bacillus. Although antibiotic treatments developed for TB of the lungs are widely available, there are no FDA-approved antibiotic treatments specifically effective for tuberculous meningitis.

A previous Johns Hopkins Children’s Center study led by Jain showed that the FDA-approved regimen of three antibiotics currently used for treating drug-resistant pulmonary TB — bedaquiline, pretomanid and linezolid (BPaL) — is not effective in treating TB meningitis, because bedaquiline and linezolid can’t efficiently cross the blood-brain barrier — a network of cells that prevents the entry of germs and toxins into the brain.

The new study used positron emission tomography (PET) scan and CT scan technology to show how the different antibiotics penetrate the brain and other areas of the body, says Jain, who is also a pediatric infectious diseases specialist at the Children’s Center. All four antibiotics distributed well in the body, but with significantly different brain and lung tissue penetration, the investigators found.

“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,” says Jain.