A therapeutic regimen comprising bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) appears to work against drug-resistant tuberculosis (TB) both in paediatric and adult patients, according to two small studies conducted in Indonesia.

On par with long-term regimen

In a preliminary evaluation of BPaLM in children with drug-resistant TB, the regimen compared favourably with the long-term regimen in terms of clinical improvement (100 percent vs 83 percent; p=0.45). [APSR 2024, abstract AO12-006]

Notably, BPaLM-treated children showed a significantly greater increase in body weight from baseline (mean change 3.9 kg, p<0.05) relative to those who received the long-term regimen (mean change 1.7 kg; p>0.05).

While laboratory parameters showed similar safety profiles between the two regimens, 83 percent of children in the long-term regimen group experienced adverse events (AEs) such as numbness, ear pain, and blurred vision as opposed to none in the BPaLM regimen group (p<0.01).

The findings indicate that the BPaLM regimen has comparable initial efficacy to the standard long-term regimen in children with drug-resistant TB but with a better safety profile, noted lead investigator Dr Dyah Ayu Shinta Lesmanawati from Padjadjaran University in Bandung, Indonesia.

“BPaLM offers a viable solution for the treatment of drug-resistant TB despite limited use in developing countries. Initially, it was recommended to adults, [but] the WHO recommended its use for children over 15 years of age in 2022,” Lesmanawati said.

“This work highlights the need for further study with larger designs and sample sizes to provide the best evidence of BPaLM regimen for [this population],” she added.

The analysis included a retrospective cohort of four children who received the BPaLM regimen and eight age- and sex-matched children who underwent treatment with the long-term regimen. The mean age of the entire sample 15.2 years, with the majority being female (67 percent) and having pulmonary TB infection (89 percent).

High response rate

In a separate study, 9 months of treatment with BPaLM or 6 months with BPaL (sans moxifloxacin) induced response in more than 90 percent of adults with drug-resistant TB.

Five of six patients who received BPaLM completed treatment, including one in whom BTA conversion occurred. Meanwhile, BPaL treatment was completed in 12 of 13 patients, with BTA conversion occurring in 10. [APSR 2024, abstract AO18-001]

Overall, the most common side effects were electrolyte imbalance (38.5 percent), peripheral neuropathy (23.1 percent), and anaemia (23.1 percent). One patient in the BPaL group experienced temporary difficulty distinguishing colours, an adverse event that was linked to linezolid. One patient in the BPaLM group died due to TB complication aggravated by severe malnutrition (BMI 14.7 kg/m²). Prolonged QTc events occurred more frequently in the BPaLM than in the BPaL group.

“Streamlined and shorter-duration regimens [are needed] to increase a successful drug-resistant TB treatment,” said first study author Dr Fabiola Anastasia Kartini Fau from the University of Indonesia, Jakarta, Indonesia.

The findings indicate that “malnutrition and linezolid usage should be carefully managed [during] BPaL/BPaLM treatment,” Fau added.

A total of 19 adults with drug-resistant TB were included in the study. The median age was 55 years in the BPaLM group and 44 years in the BPaL group. Most patients had type 2 diabetes (38.5 percent) and prior TB (30.7 percent).