Mutidrug-resistant tuberculosis, defined as TB is more likely to be caused by speedy drug metabolism in certain patients rather than by inconsistent doses, according to researchers. The finding may lead to better treatments for one of the world’s most infectious diseases.
Researchers from the University of Texas Southwestern Medical Center conducted an experiment using a sophisticated research model and found that their results seemed to challenge the current approach endorsed by the World Health Organization.
With a system of high tech test tubes researchers called “glass mouse” they were able to mimic standard therapy being given daily for 28 to 56 days, with dosing adherence that varied between 0 to 100 percent.
Researchers found that non-adherence – which includes physicians giving inappropriate treatment or patients missing doses of failing to complete their treatment - did not lead to multidrug resistance or the development of any drug resistance in repeated experiments, even when treatment failed.
“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,” Tawanda Gumbo, associate professor of internal medicine and lead author of the study said.
Gumbo and his team used computer simulations based on 10,000 TB patients in Cape Town, South Africa and found that one percent of all TB patients with perfect treatment adherence developed drug resistance because their bodies cleared the drugs from their bodies more quickly.
The body identifies the drugs as foreign chemicals and tries to cleanse itself of it. A population of individuals with a genetic trait of high drug metabolism had been found in an area of South Africa that has a high rate of multidrug- resistant TB.
Patients with high drug metabolism and receiving standard doses of drugs end up with concentrations in their bodies that are too low to kill the TB bacillus and drug resistance develops, Gumbo explained.
Tuberculosis is a common illness, and accounts for 3 percent of deaths in many countries, researchers said.
“Although effective therapy exists, there are still cases of treatment failure and drug resistance remains a threat,” Gumbo said.
Currently, the standard method of treatment is called the directly observed therapy-short-course strategy (DOTS), which is a treatment consisting of a cocktail of drugs and is taken under the supervision of health care workers who sometimes must travel to isolated villages.
“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,” said Gumbo.
Researchers concluded that based on the results of this study - that non-adherence alone is insufficient for the development of multidrug- resistant TB - it could be more cost-effective to measure patients’ drug concentrations during treatment and mediate with increases in dosage depending on how quickly their bodies clear the drugs from their systems.