Outcomes, safety of weight-based bedaquiline in children with multidrug-resistant TB

Weight-based dosing of bedaquiline for multidrug/rifampicin-resistant (MDR/RR) tuberculosis (TB) infection was safe and effective among children with and without HIV coinfection, according to findings published in Clinical Infectious Diseases.

Between 2015 and 2020, researchers in South Africa evaluated the pharmacokinetics and safety of weight-based bedaquiline among children (N=15) aged between 6 and 17 years with MDR/RR-TB infection. After treatment initiation, each patient underwent pharmacokinetic sampling between weeks 2 and 16. The pharmacokinetic target exposure was a weekly area under the curve (AUC) concentration of 187 μg/mL/h by week 24, which was the mean exposure observed among adult patients. Safety was evaluated once or twice monthly.

Among patients included in the analysis, the median age was 13.6 (IQR, 11.5-13.9) years, 46.7% were boys, and 66.7% were multiracial. In addition, the median weight-for-age Z-score was -1.48 (IQR, -2.36 to -0.68), 86.7% had bacteriologically confirmed TB infection, 60.0% had rifampicin and isoniazid resistant infections, 80.0% had pulmonary TB infection, and 20.0% had HIV coinfection.

The median treatment duration was 11.5 months, and all outcomes were successful. In addition, no significant effects were observed for age, race/ethnicity, HIV status, or method of medication administration (crushed, whole, or dispersed in water).

Bedaquiline and N-monodesmethyl metabolite concentrations were decreased compared with adult concentrations simulated in a previously published model. At week 24 of bedaquiline treatment, the median AUC was 127 (IQR, 75.2-173.2) μg/mL/h among all patients, 161.6 (IQR, 91.4-165.1) μg/mL/h/ among those weighing up to 30 kg, and 112.5 (IQR, 71.2-173.9) μg/mL/h among weighing more than 30 kg. In addition, the target exposure was achieved in only 3 patients, 2 of whom weighed more than 30 kg.

A total of 27 adverse events were reported, of which vomiting (n=5), increased alanine transaminase (n=5), and acneiform rash (n=3) were the most common. With the exception of grade 3 arthritis and arthralgia events in 1 patient, all other events were of mild or moderate severity.

This study was limited by its small sample size, sampling method, and the inability to characterize the pharmacokinetic profile of bedaquiline among children without the adult model.

According to the researchers, “further evaluation of… [pediatric] formulations of bedaquiline in…children [younger than] 6 years of age and [in] those with HIV [coinfection] should be prioritized to ensure access to effective, safe, and tolerable treatment regimens for children with MDR/RR-TB.”