Multidrug-resistant tuberculosis could be caused by faster drug metabolism

A new study demonstrated that multidrug-resistant tuberculosis is more likely caused by a faster drug metabolism in patients rather than the administration of inconsistent dosages of antibiotics.

The study, performed by Southwestern Medical Center and published in The Journal of Infectious Diseases, was performed using a sophisticated research model known as a "glass mouse," according to

If the results are confirmed by further research, experts believe new ways to treat MDR-TB can be developed.

“Tuberculosis is a common ailment, accounting for up to three percent of all deaths in many countries," Dr. Tawanda Gumbo, a senior author of the study, said, reports. "Although effective therapy exists, there are still cases of treatment failure and drug resistance remains a threat."

The study could challenge the World Health Organization's current approach to dealing with MDR-TB. The WHO uses a directly observed therapy-short-course strategy that requires the administration of a cocktail of drugs under the supervision of healthcare workers who must often travel to isolated villages to treat the infected. It is a difficult and time-consuming process that takes months to complete for each patient.

“Every TB patient is supposed to be watched as they swallow their pills in order to increase adherence and decrease emergence of drug resistance. This is the most expensive part of the program, but has been felt to be cost-effective since it improves compliance,” Dr. Gumbo said, according to

The Southwestern Medical Center team performed the study using a complex system of high-tech test tubes they dubbed a "glass mouse." The system mimicked the standard therapy given daily to patients for 28 to 56 days, with dosage adherence varying between zero to 100 percent. Non-adherence was noted to be a failure to take the dose 60 percent of the time or more.

According to Dr. Gumbo, the body sees the drugs as foreign chemicals and tries to rid itself of them as quickly as it can.

“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," Gumbo said, reports. "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."

Computer simulations based on 10,000 TB patients in South Africa showed that one percent of all TB patients with perfect adherence to the treatment schedule still developed drug resistance because their bodies' metabolism cleared the drugs more quickly.

In a population of individuals found in South Africa with a genetic trait that helps speed the process further, there is also a high rate of MDR-TB. In that population, patients who receive standard doses of TB drugs generally end up with concentrations that are too low to kill the TB bacteria and drug resistance results.