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Delamanid, a new 6-nitro-2,3-dihydroimidazo[2,1-b]oxazole for the management of tuberculosis resistant to at least isoniazid and rifampicin

2013; Taylor & Francis; Volume: 2; Issue: 1 Linguagem: Inglês

10.1517/21678707.2014.863729

2167-8707

Andreas H. Diacon, Florian von Groote-Bidlingmaier, Peter R. Donald,

Mycobacterium research and diagnosis

Introduction: Novel therapeutic agents are urgently needed to combat drug-resistant tuberculosis. Delamanid is a new 6-nitro-2,3-dihydroimidazo[2,1-b]oxazole developed from a new chemical group to which no resistance exists. Preclinical experience found delamanid efficacious with a good safety profile except for QT prolongation; in vitro no interaction, inhibitory nor stimulatory with human and animal liver microsomes or a range of CYP enzymes have been demonstrated; interactions with antiretroviral agents are unlikely but this must still be demonstrated in clinical trials. A dose-ranging early bactericidal activity study provided proof of concept, and a controlled trial over the first 8 weeks of multidrug-resistant tuberculosis treatment found accelerated sputum culture negativity. Delamanid is in ongoing clinical trials in children, adults and HIV-infected adults receiving antiretroviral treatment. Areas covered: Using keywords, such as imidazooxazole, nitroimidazoles, OPC-67683, delamanid and antituberculosis drugs, the literature concerning the development and assessment, both in vitro and in vivo, of a new antituberculosis drug, delamanid was reviewed. Expert opinion: In view of efficacy, absence of major toxicity thus far and probable lack of interaction with antiretroviral agents, delamanid is a potential addition to the therapeutic armamentarium for tuberculosis.