While researchers found that a type of blood pressure medication may be effective at overcoming some drug-resistant tuberculosis (TB), they also discovered that the Mycobacterium TB bacterium, which causes the disease, might be resistant to treatment in more people than previously thought.
In the first study, published in The Journal of Infectious Diseases, researchers used an experimental apparatus to simulate the way TB bacteria grow in the human lung. When they exposed the bacteria to ethambutol and isoniazid—two drugs commonly used to treat the disease—the bacterial cells activated a cellular mechanism that pumps each drug out of the cells. The pumping action enables the rapid emergence of high-level resistance to the drugs whether administered together or individually.
Resistance was drastically reduced, however, when the researchers gave the blood-pressure drug reserpine—which is known to block this pumping action—to the TB cells before administering ethambutol and isoniazid.
In the second study, published in Antimicrobial Agents and Chemotherapy, the researchers found that more people might harbor drug-resistant TB than currently believed, because tests that detect the TB bacteria’s resistance do not account for variations in height, weight, and other factors among TB patients. The guidelines for testing whether a person is infected with a drug-resistant TB strain were developed over 40 years ago.
The study again simulated TB in the human lung and virtually simulated eight clinical trials involving 10,000 patients. The computer simulation factored in pharmacokinetics—how a body handles a drug based on heterogeneous factors—to determine how likely a dose of a given drug is to kill TB.
The researchers found that the concentrations typically used in practice are too low, leading people to think they have treatable TB, when in fact their disease might be resistant to common drugs.
“There is likely more multidrug-resistant TB than previously thought—possibly up to four times as much,” Tawanda Gumbo, MD, associate professor of internal medicine at UT Southwestern Medical Center and senior author of the studies. “That means some people may be getting underdosed with medicine weaker than the disease, and they die.”