Second-Line Drugs Can Successfully Treat Children with Multidrug-Resistant TB

Approximately 32,000 children are affected by multidrug-resistant tuberculosis (MDR-TB) each year. The resistance typically is against tuberculosis treatment drugs isoniazid and rifampicin. When these drugs cannot be used, a longer duration of therapy and more toxic drugs are required to treat these infections.

In a new study published in PLOS Medicine, a team of investigators performed a systematic literature review and meta-analysis of individual patient data detailing outcomes in children treated for MDR-TB. The investigators found that 78% of the children included in the studies had successful treatment outcomes when treated with second-line MDR-TB drugs.

This research was used to inform the World Health Organization’s revised treatment guidelines for children with resistant TB infections.

"To date, little has been known about the optimal treatment for these children,” said Anneke Hesseling, MD, PhD, distinguished professor of pediatrics and child health, Desmond Tutu TB Center, Stellenbosch University, and an author on the study, said in a recent statement, “This review, therefore, gives vitally important information as to potential outcomes and some very good news for the TB field."

The team collected published reports from online databases and reviewed unpublished content which included conference abstracts and research referred to the team by TB experts in the field. Investigators declared a cohort eligible for inclusion if it included at least 3 children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB and had reported treatment options. Ultimately, investigators identified 33 studies to include in their review; twenty-eight of the studies had patient data available.

A total of 975 children from 18 countries were analyzed in the data pool. Of all participants, 731 (75%) had bacteriologically confirmed MDR-TB and 244 (25%) had clinically diagnosed TB. The median age of the children was 7.1 years.

Overall, 764 of 975 (78%) were reported to have had successful treatment outcomes with second-line medications: 548 of 731(75%) of confirmed and 216 of 244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%—19%, p < 0.001).

Additionally, of 910 children (93%) with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, patients with confirmed MDR-TB were likely to be older, to be infected with HIV, to be malnourished and to have severe TB on chest radiograph (p <0.001 for all), according to the study authors.

Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV and had not received antiretroviral treatment during treatment for MDR-TB. In comparison, treatment was successful in 82% of children infected with HIV who received antiretroviral treatment during MDR-TB therapy (absolute difference 26%, 95% CI 5%—48%, p = 0.006).

The investigators also reported that the use of second-line injectable agents and high-dose isoniazid (15— 20 mg/kg/day) were associated with treatment success in children with confirmed MDR-TB (adjusted odds ratio [aOR] 2.9, 95% CI 1.0–8.3, p = 0.041 and aOR 5.9, 95% CI 1.7–20.5, p = 0.007, respectively).

Some limitations of this study include that it is difficult to estimate the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician’s perception of illness, with resulting potential for bias.

These findings suggest that children respond well to MDR-TB treatment. Furthermore, the low success rate in children infected with HIV who did not receive antiretroviral therapy during their MDR-TB treatment reveals the need for antiretroviral therapy in children with MDR-TB.

Future research on the effects of individual drugs for the treatment of MDR-TB should be conducted, according to the investigators.