Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis in Children: The Role of Bedaquiline and Delamanid.

Francesco Pecora,Giulia Dal Canto,Piero Veronese,Susanna Esposito

doi:10.3390/microorganisms9051074

Francesco Pecora, Giulia Dal Canto + Show 2 more

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https://doi.org/10.3390/microorganisms9051074

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Abstract

Multidrug-resistant (MDR) tuberculosis (TB) has been emerging at an alarming rate over the last few years. It has been estimated that about 3% of all pediatric TB is MDR, meaning about 30,000 cases each year. Although most children with MDR-TB can be successfully treated, up to five years ago effective treatment was associated with a high incidence of severe adverse effects and patients with extensively drug-resistant (XDR) TB had limited treatment options and no standard regimen. The main objective of this manuscript is to discuss our present knowledge of the management of MDR- and XDR-TB in children, focusing on the characteristics and available evidence on the use of two promising new drugs: bedaquiline and delamanid. PubMed was used to search for all of the studies published up to November 2020 using key words such as “bedaquiline” and “delamanid” and “children” and “multidrug-resistant tuberculosis” and “extensively drug-resistant tuberculosis”. The search was limited to articles published in English and providing evidence-based data. Although data on pediatric population are limited and more studies are needed to confirm the efficacy and safety of bedaquiline and delamanid, their use in children with MDR-TB/XDR-TB appears to have good tolerability and efficacy. However, more evidence on these new anti-TB drugs is needed to better guide their use in children in order to design effective shorter regimens and reduce adverse effects, drug interactions, and therapeutic failure.

Highlights

Published: 17 May 2021Tuberculosis (TB) causes even more deaths each year than any other bacterial infection [1]
Most children with MDR-TB can be successfully treated, up to five years ago effective treatment was associated with a high incidence of severe adverse effects and patients with XDR-TB had limited treatment options and no standard regimen [9,10,11,12]
For MDR-TB, longer treatment regimens are recommended, and the choice of an effective all-oral regimen is suggested in several guidelines

Summary

Introduction

Published: 17 May 2021Tuberculosis (TB) causes even more deaths each year than any other bacterial infection [1]. The burden of disease is very heterogeneous among countries, with the global average being around 130 new cases per 100,000 population per year. TB deaths among HIV-negative people, in 2018, were estimated to be 1.2 million (range 1.1–1.3 million), and 251,000 deaths (range 223,000–281,000) among. In countries with high HIV prevalence, the peak age prevalence of TB has shifted towards younger adults. These adults are often parents of young children, increasing the exposure of children to TB [3,4]. Delamanid 50 mg td + BR for 10 days (pediatric formulation) td + BR for 10 days. Delamanid from 5 mg to 10 mg td (pediatric formulation) based on weight measurements + Delamanid 50 mg td for Delamanid 25 mg (pediatric formulation) td for 182 days + BR for Delamanid from 5 mg qd to 10 mg td (pediatric formulation) based on weight measurements for Pharmacokinetic, safety, tolerability, and efficacy of delamanid

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