New and Repurposed Drugs for Pediatric Multidrug-Resistant Tuberculosis. Practice-based Recommendations

Abstract

It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.

An overview of new antitubercular drugs, drug candidates, and their targets

“…After administration, linezolid maintains appreciable level in blood serum, which means less frequent dosage requirement in larger intervals of time. Another key characteristic of linezolid is its excellent penetration into the cerebrospinal fluid (CSF) which makes it appropriate for the treatment of MDR‐TB meningitis . The presence of food does not have much effect on the absorption of linezolid, so this antibiotic could be taken both with or without meals.…”

“…Another key characteristic of linezolid is its excellent penetration into the cerebrospinal fluid (CSF) which makes it appropriate for the treatment of MDR-TB meningitis. 97 The presence of food does not have much effect on the absorption of linezolid, so this antibiotic could be taken both with or without meals. Metabolism of linezolid occurs through nonenzymatic oxidation and the metabolites do not show any antibacterial activity.…”

Multidrug-resistant tuberculosis and beyond: an updated analysis of the current evidence on bedaquiline

“…isolation of Mycobacterium tuberculosis with execution of DST. Thus, empirical administration of second-and third-line anti-TB drugs mainly relies on medical history related to previous contacts [54][55][56][57].…”

“…Given these arguments, only specialised centres should eventually manage these difficult-to-treat cases, according to the criteria proposed [20], possibly under the guidance of a panel of experts such as the TB Consilium [62,67]. In paediatric settings, no published evidence is still available, although clinically-based recommendations have been recently published [57] and a recent study by Medecines Sans Frontieres (MSF) reports on the actual needs to increase the availability of such new drugs [68]. Interestingly, a preliminary report from MSF projects recently presented in Liverpool on 24 cases [69] seems to be encouraging.…”

Current therapies for the treatment of multidrug-resistant tuberculosis in children in India

“…Caution should be applied while combining delamanid with other drugs that have the potential of prolonging QT. There is no noted interaction of delamanid with the antiretroviral agents [74]. Hypoalbunemia may increase the potential of delamanid to prolong QT; albumin levels should also be monitored while prescribing delamanid [75].…”