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High rate of culture conversion observed with bedaqualine for TB
Compassionate use of bedaquiline, combined with other drugs, resulted in culture conversion in almost all patients with multidrug-resistant tuberculosis after 6 months of treatment, according to researchers from France.
“Following the recent ‘fast-track’ approval of bedaquiline by the FDA, it is crucial to increase the amount of clinical evidence on this compound,” researchers for the MDR-TB Management Group of the French National Reference Center for Mycobacteria and the Physicians of the French MDR-TB Cohort, wrote in Clinical Infectious Diseases. “Our results show that bedaquiline-containing regimens used in accordance with provisional guidelines led to a high rate (97%) of culture conversion after 6 months for these difficult-to-treat patients. This is higher than in the randomized trials performed so far.”
The researchers performed a retrospective cohort study that included 35 patients with MDR-TB who received at least 1 month of bedaquiline (Sirturo, Janssen Therapeutics) for compassionate use between from January 2010 to July 2013. Nineteen of the patients had extensively drug-resistant TB. Twenty-six of the patients received bedaquiline as part of their initial MDR-TB treatment; the other nine patients had received a median of 85 days of treatment before bedaquiline initiation. All patients received a median of four additional antibiotics.
Among 29 patients who had culture-positive pulmonary TB at bedaquiline initiation, 28 achieved culture conversion after 6 months of treatment. Sputum-smear conversion occurred in 20 of the 29 patients initially smear-positive. The median time to culture conversion was 85 days, and the median time to sputum-smear conversion was 103 days.
In a multivariable analysis, the researchers found that the presence of lung cavities (HR=0.04; 95% CI, 0.01-0.2) and a hepatitis C virus infection (HR=0.21; 95% CI, 0.08-0.54) were associated with slower time to culture conversion. Treatment with any fluoroquinolone for 30 days or more, however, was associated with a faster time to culture conversion (HR=3.28; 95% CI, 1.3-8.27).
Seven patients experienced QT interval increase of at least 60 ms from baseline, which led to two patients discontinuing treatment. Two patients also experienced severe liver enzyme elevation. One patient died, but the death was unrelated to TB or anti-TB treatment.
“Of interest, bedaquiline was combined with linezolid in 94% of our patients,” the researchers wrote. “The relevant role of linezolid in the treatment of MDR-TB and particularly of fluoroquinolone-resistant strains has been recently highlighted and could partially explain our satisfactory results.”
Disclosure: Three researchers report receiving fees, payment or research grants from Janssen Pharmaceuticals or AstraZeneca.