New treatment regimens for highly drug-resistant tuberculosis

A new study conducted by TB Alliance has shown that the BPaL regimen for the treatment of highly drug-resistant tuberculosis remained effective when the dosage of linezolid was reduced. Researchers also noted a decrease in side effects associated with the reduced linezolid dose.

The results of the study were presented at the 11th IAS 2021 Scientific Conference.

The BPaL regimen, which combines the antibiotics bedaquiline, pretomanid and linezolid, received its first regulatory approval in August 2019 for use against highly drug-resistant TB strains. Historically treatment has lasted 18 months, and in some cases even longer, with a success rate of around 43%.

"The study proves that the BPaL scheme can be optimized and made even easier to use. Until recently, patients with high drug-resistant tuberculosis had to suffer a combination of as many as eight antibiotics for 18 months or longer," Dr. Mel Spigelman said.

Research and results

The study took place in Georgia, Moldova, Russia and South Africa. 181 patients with highly drug-resistance TB forms took part in the BPaL regimen tests. Among the participants were 36 people (20%) living with HIV.

Participants were divided into four groups depending on the form of TB and treatment protocols. Patients were treated with bedaquiline, pretomanid and linezolid at different doses with different durations for upto six months.

According to the data:

• Group 1 - 1200mg over 6 months (the highest dose of linezolid) were cured in 93% of cases.
• Group 2 - 1200mg over 2 months were cured in 89% of cases.
• Group 3 - 600mg over 6 months were cured in 91% of cases.
• Group 4 -  600mg over 2 months were cured in 84% of cases.

The dosages of bedaquiline and pretomanid were the same in all four groups. Side effects reported by at least 10% of participants included peripheral neuropathy for 38% of those who received 1200mg of linezolid over 6 months; 24% of those who received 1200mg of linezolid over 2 months; 24% of those who received 600mg of linezolid over 6 months; 13% of those who received 600mg of linezolid over 2 months.

Researchers have also found that during treatment, patients had reduced haemoglobin levels associated with the effects of linezolid (22% from the first group; 17% from the second group; 2% from the third; 7% from the fourth group).

TB Alliance plans to provide ZeNix data to a peer-reviewed publication.

"The results of this study are very encouraging. With the dose reduction and/or duration of linezolid, we can still offer patients a high chance of recovery in just six months," said Francesca Conradi, MD, chief researcher at ZeNix.