“Until now, when treating patients, we’ve relied on a needle biopsy,” says Tucker. “We’ve assumed that what’s happening at the tip of the needle at one time point in a sample is what’s happening throughout the affected organ.” The new results in the rabbit model, she says, suggest that it’s not that simple, at least in the animals. The penetration of rifampin varied among TBM lesions even within a single animal, and changed over the course of the long treatment timeline.
The researchers also gave the tagged version of the drug to 10 adult human TB patients already receiving rifampin therapy. The patients were scanned at the Johns Hopkins PET Center in Baltimore, and these studies were performed under Food and Drug Administration guidelines for new PET tracers. One of the patients, a 24-year-old female, had TBM. Similar to the results in rabbits, a PET scan showed that penetration of the drug into the patient’s brain lesions was limited to less than 5 percent.
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The findings, the researchers say, help advance understanding of why current drug treatments for TBM may not be as effective. And they say the PET approach offers a potential way to optimize the treatment of TBM, to ensure that enough drug is reaching the infected lesions.
“If further research in animals and humans confirms that rifampin and other anti-TB drugs penetrate differently into their brains,” says Ordonez, “we foresee that imaging can help us figure out the concentration of drug needed and tailor the dose for individual patients.”
The team also expects that the rabbit model of TBM can be used to answer key questions about the disease and its treatment, including what baseline levels of antibiotics are required to penetrate brain lesions more fully.
“We used to think we could just give a drug and patients should get better,” says Jain. “Now, we have tools to measure the nuances that make a difference. PET could be used to study other antibiotics and also allow precision medicine approaches in resource-rich settings, such as the U.S. for other serious infections including MRSA (methicillin-resistant Staphylococcus aureus).”
Other authors on the paper include Brittaney Ritchie, Mariah Klunk, Richa Sharma, Yong Chang, Julian Sanchez-Bautista, Sarah Frey, Martin Lodge, Steven Rowe, Daniel Holt, William Mathews, Robert Dannals, Carlos Pardo-Villamizar and Sujatha Kannan of Johns Hopkins, Beatriz Guglieri-Lopez, Joga Gobburu and Vijay Ivaturi of the University of Maryland, and Charles Peloquin of the University of Florida.
