Study warns of emerging and spreading resistance to new drug-resistant tuberculosis treatments

New research shows that resistance to shorter, less toxic drug regimens for multidrug-resistant tuberculosis (MDR-TB) is emerging and spreading among patients.

in letter last week, New England Medical Journal, Scientists from the Swiss Institute of Tropical Public Health (TPH) and the Georgia National Center for Tuberculosis and Lung Diseases, Mycobacterium tuberculosis Genome analysis from 27 countries identifies more than 500 strains of MDR-TB with additional resistance to at least one compound in the BPaL/M (bedaquiline, pretomanid, linezolid with or without moxifloxacin) regimen .

More than a quarter of those strains appear to have been transmitted between patients.

Approved by the World Health Organization (WHO) in 2022, BPaL/M is a 6-month all-oral drug regimen that lasts more than 15 months and replaces previous MDRs that included injectable drugs with severe symptoms. -Significantly shorter than the TB regimen. and painful side effects. BPaL/M also has a much higher cure rate of more than 90%, compared to less than 50% with previous regimens, according to randomized trial data.

The letter authors note that while much of the global burden of multidrug-resistant tuberculosis is due to patient-to-patient spread, the acquisition of further resistance to BPaL/M compounds will reduce their competitiveness and make them less transmissible. He said he thought it was a possibility. They conducted a study to investigate that theory.

“This new treatment is a game-changer for patients suffering from multidrug-resistant tuberculosis, but we knew it would be difficult to outwit it. Mycobacterium tuberculosisthe bacterium that causes tuberculosis,” Dr. Sébastien Gagneau, head of the Department of Medical Parasitology and Infection Biology at TPH Switzerland and lead study author, said in the paper. press release. “Therefore, it was critical to study how Mycobacterium tuberculosis responds to the global rollout of this new treatment.”

Genomic analysis reveals resistance mutations

The researchers first analyzed the genomes of 6,926 people. Mycobacterium tuberculosis Isolates collected over 13 years in Georgia, a country with a high burden of MDR-TB. From these isolates, 60 tuberculosis strains harbored mutations conferring resistance to at least one of the following: isoniazid and rifampicin (first- and second-line drugs for the treatment of drug-susceptible tuberculosis), fluoroquinolones, and BPaL/M drugs. The strain was identified.

Further analysis of these strains, which were defined as “highly drug resistant,” showed that 16 out of 58 (28%) were classified into four genomic clusters, with all strains having identical mutational profiles. It was found to indicate patient-to-patient transmission.

To see if transmission of these highly drug-resistant TB strains was occurring elsewhere, the researchers then analyzed 81,576 genomes from 26 countries. They identified 454 highly drug-resistant strains, with 117 of 420 (28%) associated with direct infection.

“The good news is that the total number of these cases is still small,” said study co-author Dr. Garo Goyg, a postdoctoral researcher at TPH in Switzerland. “However, even though it has only been two years since the WHO approved a new treatment, more than a quarter of these highly drug-resistant cases are due to patient-to-patient transmission. The fact that there is is a matter of concern.”

The research team also found that nine strains carried resistance mutations to all BPaL/M drugs. The strains were found in four countries: Belarus, Georgia, India and South Africa, and were classified as “fully drug-resistant”.

…more than a quarter of these highly drug-resistant cases are due to patient-to-patient transmission, even though it has been only two years since the WHO approved a new treatment. The fact that there is is a cause for concern.

The WHO estimates that 400,000 people will develop MDR-TB worldwide in 2023. investigation A percentage of National Tuberculosis Program staff predicts that BPAL/M regimens will reach 78% of MDR-TB patients by 2026. Shortened regimens are expected to improve intake and adherence.

But the study authors caution that their findings suggest that without improvements in diagnostic capabilities, infection control, and surveillance, the therapy's longevity may be at risk.