Washington: Prescribing antibiotic doses once or twice a week for tuberculosis (TB) treatment are more likely to lead to drug resistant strains than daily antibiotic regimens, a computer model of the disease has shown. The finding, from a University of Michigan study, could help inform the treatment of the roughly 10 million people worldwide who fall ill with tuberculosis each year, researchers said.
Active tuberculosis is notoriously difficult to treat, and the spread of antibiotic-resistant TB is increasing. Current drug regimens start with four different antibiotics for the first two months, dropping to two antibiotics for four more months of treatment.
“Experimentalists can’t test thousands and thousands of antibiotic regimens, but we can,” said Jennifer Linderman, U-M professor of chemical engineering and biomedical engineering. Experiments with animals are expensive and time-consuming, and present ethical dilemmas, so the team is developing a reliable computer model of tuberculosis that can test many drug combinations and treatment regimens quickly.
Their study demonstrates how treatments with the standard antibiotics isoniazid and rifampin fare when taken according to different regimens approved by the US Centre for Disease Control. These include larger doses a few times per week and smaller daily doses.
The computer simulations showed that daily treatment with both antibiotics is the best way to go, but even then, the drugs have a hard time killing off all of the TB bacteria. Part of the problem is that bacteria can hide out in tumour-like lesions called granulomas.
“The drugs actually have to penetrate into the core of this granuloma,” said Denise Kirschner, U-M professor of microbiology and immunology. Kirschner said the bacteria can protect themselves further by going into a passive state, in which they stop trying to reproduce.
“If it’s just sitting there, the drug is not going to have as strong an effect on it, which is why you have to treat for six months. You need to catch those bacteria in the few moments when they divide,” she said. Looking for a way to kill these holdouts, the team found that upping the doses to nine per week, perhaps with patients taking morning and evening doses twice per week, they were able to cut the time until the bacteria were wiped out by about 10 days, on average.
They also explored what drug properties to target to make isoniazid and rifampin more effective. For instance, they found that if the cells in the body absorbed about 20 per cent less isoniazid, allowing the drug more time to kill TB bacteria, it could drop the treatment failure rate from 1 per cent to nearly 0 per cent. This change could represent a hundred thousand more successful treatments per year, researchers said.
