Current guidelines recommend bedaquiline (BDQ) for 6 months as part of longer 18–20-month treatment regimens for drug-resistant tuberculosis. Evidence supports the safety of using BDQ beyond 6 months. But there is limited data on whether prolonged use improves treatment success.
A recent study published in the American Journal of Respiratory and Critical Care Medicine aimed to find out.
Treating tuberculosis
Mycobacterium tuberculosis is one of the deadliest pathogens that has been infecting humans for thousands of years. When it infects someone, the infection or the disease is termed tuberculosis. It can affect various parts of the human body but lungs are its most common target.
Since tuberculosis is a bacterial infection, it is usually treated with antibiotics. However, what sets it apart is its unusually slow growth rate. Most antibiotics work when the bacteria are actively growing. Mycobacterium tuberculosis likes to stay dormant for long periods.
When the bacteria eventually start to grow, they do so in an unsymmetrical manner by being at different stages of their life cycle. Therefore, one type of antibiotic does not work against all of them. To overcome this challenge, a combination of various drugs, such as isoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin, is used [1].
Yet, the major challenge in the treatment of tuberculosis is drug resistance. Over time, bacteria become resistant to the standard antibiotics [2]. This means that it does not respond to the standard antibiotics and is deemed multidrug-resistant tuberculosis (MDR-TB).
The need for optimal BDQ duration
MDR-TB requires treatment with second-line drugs that can have more side effects. One of these second-line medications is BDQ, which was approved in 2012 [3]. However, a lot is still not clear about the clinical use of BDQ.
Understanding the optimal duration of BDQ is important. If effective, longer use could potentially replace other drugs with more concerning side effect profiles. But unnecessarily prolonging BDQ could lead to wasted resources and additional burden to the patients.
Analyzing BDQ use in over 1,400 MDR-TB patients
To investigate this question, researchers analyzed data from a large observational cohort study conducted in 17 countries between 2015-2018 [4].
The study included 1,468 patients treated for MDR-TB with customized regimens containing BDQ. The patients received BDQ for the following durations:
6 months (615 patients)
7-11 months (552 patients)
12 months or longer (301 patients)
The regimens typically contained 4-5 likely effective medications, including repurposed TB drugs like linezolid and clofazimine.
The researchers compared the probability of successful treatment between the groups using advanced statistical techniques to minimize bias.
Key findings: No clear benefit of longer treatment
The results showed:
The success rate was 85% with 6 months of BDQ. It was 77% with 7-11 months and 86% with 12+ months.
Compared to 6 months, the likelihood of success was 9% lower with 7-11 months and 1% higher with 12+ months.
Takeaway points
This large real-world study found no evidence that using BDQ for more than 6 months improved treatment outcomes. The 85% success rate with 6 months was excellent. For MDR-TB patients receiving potent 4+ drug regimens, 6 months of BDQ appears adequate.
However, the analysis did not include patients with extensive disease or less effective accompanying regimens. It is possible that these groups may benefit from longer BDQ or other drug durations. The researchers also concluded that serious biases in less sophisticated analyses wrongly suggested longer BDQ use was more effective.
Future studies are still needed to definitively determine optimal BDQ use. But these results help guide practice while additional evidence is gathered.
References
1. “Treatment of tuberculosis patients,” in Implementing the WHO Stop TB Strategy: A Handbook for National Tuberculosis Control Programmes, World Health Organization, 2008.
2. J. B. Nachega and R. E. Chaisson, “Tuberculosis Drug Resistance: A Global Threat,” Clinical Infectious Diseases, vol. 36, no. Supplement_1, pp. S24–S30, Jan. 2003, doi: 10.1086/344657.
3. R. Mahajan, “Bedaquiline: First FDA-approved tuberculosis drug in 40 years,” Int J Appl Basic Med Res, vol. 3, no. 1, pp. 1–2, 2013, doi: 10.4103/2229-516X.112228.
4. L. Trevisi et al., “Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis,” Am J Respir Crit Care Med, vol. 207, no. 11, pp. 1525–1532, Jun. 2023, doi: 10.1164/rccm.202211-2125OC.
