multidrug-resistant tuberculosis and QTc prolongation

Q: In the treatment of Multi-Drug resistant Tuberculosis (MDR-TB), which drug requires close monitoring for QTc prolongation? Select one

A) Bedaquiline 

B) Pretomanid 

C) Linezolid 

D) Moxifloxacin 

E) Levofloxacin 

Answer: A

Bedaquiline received full FDA approval in 2024 as part of combination therapy for both adult and pediatric patients (>5 years and ≥15 kg) with pulmonary TB resistant to at least rifampicin and isoniazid (INH).

Bedaquiline can cause QT prolongation, requiring close electrocardiogram (EKG) monitoring before and during the treatment, or as needed if symptoms occur, such as syncope. Patients with higher comorbidities should be watched very closely, such as patients with an underlying history of torsade de pointes, congenital long QT syndrome, hypothyroidism, bradyarrhythmia, uncompensated heart failure, electrolyte disturbances, and those on other drugs prone to cause QTc prolongations. 

Ideally, bedaquiline should be discontinued if QTc-F >500 ms. To make things more complicated, bedaquiline has a terminal serum half-life of four to five months.

#Pharmacology

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#cardiology

References:

1. Katrak S, Lowenthal P, Shen R, True L, Henry L, Barry P. Bedaquiline for multidrug-resistant tuberculosis and QTc prolongation in California. J Clin Tuberc Other Mycobact Dis. 2021 Jan 10;23:100216. doi: 10.1016/j.jctube.2021.100216. PMID: 33598568; PMCID: PMC7868725.

2. World Health Organization. Key updates to the treatment of drug-resistant tuberculosis: rapid communication, June 2024. 2024. https://www.who.int/publications/i/item/B09123 (Accessed on August 25, 2025)

3. Schnippel K, Ndjeka N, Maartens G, et al. Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study. Lancet Respir Med 2018; 6:699.

4. Perrineau S, Lachâtre M, Lê MP, et al. Long-term plasma pharmacokinetics of bedaquiline for multidrug- and extensively drug-resistant tuberculosis. Int J Tuberc Lung Dis 2019; 23:99.