Multidrug resistant tuberculosis (TB) is more likely caused in patients by speedy drug metabolism rather than inconsistent doses, as is widely believed, scientists have revealed.
The finding may lead to better ways to treat one of the world's major infectious diseases.
The team from the UT Southwestern Medical Center included Drs. Shashikant Srivastava, Tawanda Gumbo and Jotam G. Pasipanodya.
In this study, UT Southwestern researchers created a sophisticated system of high-tech test tubes, which they called a "glass mouse," that mimicked standard therapy being given daily for 28 to 56 days, with dosing adherence varying between 0 percent and 100 percent.
The threshold for defined non-adherence (failure to take a required dose of medication) was reached at 60 percent of the time or more.
"The first main finding in our laboratory model was that in fact non-adherence did not lead to multidrug resistance or emergence of any drug resistance in repeated studies, even when therapy failed. In fact, even when we started with a bacterial population that had been spiked with drug-resistant bacteria, non-adherence still did not lead to drug resistance," said Dr. Tawanda Gumbo, associate professor of internal medicine and senior author of the study.
In fact, using computer simulations based on 10,000 TB patients in Cape Town, South Africa, the researchers discovered that approximately 1 percent of all TB patients with perfect adherence still developed drug resistance because they cleared the drugs from their bodies more quickly.
The body sees drugs as foreign chemicals and tries to rid itself of them, Dr. Gumbo said. A population of individuals with a genetic trait that speeds the process has been found in one area of South Africa that has a high rate of multidrug-resistant TB.
In that population, patients who receive standard doses of drugs end up with concentrations in their bodies that are too low to kill the TB bacillus and drug resistance develops, he said.
"These data, based on our preclinical model, show that non-adherence alone is insufficient for the emergence of multidrug-resistant TB," Dr. Gumbo said.
"It might be more cost-effective to measure patients' drug concentrations during treatment and intervene with dosage increases in those who quickly clear the drugs from their systems," he added.
The finding has been published in The Journal of Infectious Diseases.