Multidrug-resistant tuberculosis and culture conversion with bedaquiline

Area of Science:

• Infectious Diseases
• Pharmacology
• Clinical Trials

Background:

• Bedaquiline, a diarylquinoline, targets mycobacterial ATP synthase.
• It has shown promise in accelerating sputum-culture conversion for multidrug-resistant tuberculosis (MDR-TB).

Purpose of the Study:

• To evaluate the efficacy and safety of bedaquiline in patients with newly diagnosed, smear-positive, multidrug-resistant tuberculosis.
• To assess the time to sputum-culture conversion and overall cure rates.

Main Methods:

• A phase 2b randomized trial involving 160 MDR-TB patients.
• Patients received either bedaquiline or placebo combined with a standard background regimen.
• Primary endpoint was time to sputum-culture conversion; follow-up was 120 weeks.

Main Results:

• Bedaquiline reduced median time to culture conversion from 125 to 83 days.
• Culture conversion rates at 24 weeks (79% vs. 58%) and 120 weeks (62% vs. 44%) were significantly higher with bedaquiline.
• 120-week cure rates were 58% for bedaquiline versus 32% for placebo (P=0.003).
• Adverse events were similar, but 10 deaths occurred in the bedaquiline group vs. 2 in placebo.

Conclusions:

• Adding bedaquiline to a background regimen for 24 weeks accelerates culture conversion and increases overall conversion rates.
• Higher cure rates were observed with bedaquiline, but a higher incidence of death was noted.
• Further investigation into the safety profile, particularly concerning mortality, is warranted.