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Substituting bedaquiline for second-line injectables improves MDR-TB treatment

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September 6, 2018

Findings from a recent study support substituting bedaquiline for second-line injectables in treatment for multidrug-resistant tuberculosis, with researchers reporting improved outcomes at 12 months compared with patients who remained on second-line injectables.

Multidrug-resistant tuberculosis (MDR-TB) infections are resistant to rifampicin and isoniazid and are associated with increased mortality and worse treatment outcomes, the researchers noted in Clinical Infectious Diseases. Second-line injectables (SLIs) are often used to treat MDR-TB but can cause substantial toxicity, leading to the discontinuation of treatment and lowering success rates, they said.

“There is a stepwise decline in the success of TB treatment as drug resistance patterns advance, and the presence of resistance to SLIs is a significant predictor of poor long-term survival in some studies,” they wrote. “Therefore, discontinuing SLIs from MDR-TB regimens without replacement by an effective drug may put patients at risk of worse outcomes and ongoing transmission of drug-resistant TB.”

According to the study, WHO has issued a conditional recommendation to use bedaquiline in patients with MDR-TB with limited treatment options, but the efficacy and safety of this now widely used strategy is unknown. WHO recently updated its treatment guidance for MDR-TB, which prioritizes oral drugs such as bedaquiline over injectables.

The researchers performed a retrospective cohort study to evaluate treatment outcome for patients with MDR-TB who substituted bedaquiline for SLIs. They included 162 patients with bedaquiline substitution and 168 matching controls. All patients were identified from the South African Electronic Drug-Resistant Tuberculosis Register, a web-based network used to manage and surveil MDR-TB in South Africa, the researchers said.

In the bedaquiline group, 29 patients initiated bedaquiline at approximately 29 days after the start of treatment. The other 127 patients in the group discontinued second-line injectable treatment at a median of 54 days, waited 44 days after SLI withdrawal and then began bedaquiline treatment.

Researchers reported unfavorable outcomes in 35 patients in the bedaquiline group and 51 in the control group. They noted that unfavorable outcomes remained significantly lower in the bedaquiline group after adjusting for age, CD4 count, HIV status and baseline smear positivity in a multivariate logistic regression model.

Only one patient had culture revision in the bedaquiline group compared with 12 patients in the control group. Researchers determined mortality was the same at 12 months, with 11 deaths in each group.

“Substituting bedaquiline for SLIs in the programmatic treatment of MDR-TB is not associated with increased mortality, and results in fewer unfavorable outcomes at 12 months compared with patients who remain on SLIs,” they concluded. “These findings provide additional evidence to support the routine inclusion of bedaquiline in MDR-TB regimens.” – by Caitlyn Stulpin

Disclosures: The authors report no relevant financial disclosures.

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