University researchers have found a way to decrease resistance to tuberculosis antibiotics.

Tuberculosis is a contagious disease that, according to the World Health Organization, causes about 1.5 million deaths per year worldwide. A common problem in treating tuberculosis occurs when patients develop resistance to antibiotics. Currently, the most common way to treat tuberculosis is by prescribing weekly or biweekly antibiotics. The team of researchers found that the most effective way to prevent resistant strains of the illness from developing in patients may be having patients take antibiotics every day.

Elsje Pienaar, a postdoctoral scholar in chemical engineering and the lead author of the study, was assisted by two University faculty members, as well as faculty members from Rutgers University and the University of Pittsburgh.

In an e-mail to The Michigan Daily, Pieenaar said tuberculosis, also known as TB, typically occurs when someone inhales bacteria from an infected person nearby. The infected bacteria then settles in the lungs, where the immune system cannot eliminate them. Though one-third of the world is infected with the TB bacterium, only between 5 and 10 percent of those cases become active. The other 90 to 95 percent progress to an infection where the patient is not sick or contagious, but they still harbor the bacteria.

Microbiology and Immunology Prof. Denise Kirschner, a co-author of the study, said populations with poor nutrition and health tend to be more susceptible to tuberculosis. Overall, health conditions, diet, access to clean water and other infections, such as HIV, also affect an individual’s susceptibility.

In 2001, Kirschner collaborated on a paper establishing a computer model that can be used to study TB. She said she has been working with that model for the past 14 years.  

In an e-mail to the Daily, Chemical Engineering Prof. Jennifer Linderman, another collaborator on the study, said the computer model allows researchers to test how well an antibiotic removes bacteria from a lung granuloma — a bacteria-containing structure that develops in the lungs following infection with tuberculosis. Because bacteria containing tuberculosis can hide in the granuloma, it’s crucial for researchers to understand how effectively antibiotics can remove bacteria from it.

The computer model allowed the researchers to alter variables to better understand the best concentration and frequency of antibiotics. Linderman said the model can provide insight into the effects of different concentrations of antibiotics in the blood, how much of the antibiotic actually gets into the granuloma and how much of the bacteria dies due to the antibiotics.

Considering two common antibiotics, Linderman said the team found many doses were too small to kill enough bacteria in granulomas.

“We tested two very common antibiotics given for TB, isoniazid and rifampin, alone and in combination,” Linderman wrote. “For some previously recommended drug regimens, we found suboptimal concentrations of antibiotics in granulomas and thus poorer killing of the bacteria.”

Kirschner said you need very high levels of antibiotics to get inside the granuloma and sustain treatment.

“Not only do you have to get the drug in the body, you have to get them inside these granulomas, and the granulomas are really dense,” Kirschner said. “And they are also heterogeneous, meaning that they are not perfectly uniform. To get the drugs everywhere, you need to have a very high level of drug.”

Linderman said the team found daily dosing improves bacterial killing and reduces the likelihood that any bacteria will stay in the granuloma at the end of the treatment period.

Though these results are promising, Kirschner said there is no study that has done every clinical trial possible comparing each different type of dose.

“Our study is not a whole-host study,” Kirschner said. “This is the first step in a large study of trying to understand how to dose in TB in a very systematic way.”

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