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

Abstract

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.

Keywords::

• antituberculosis treatment
• delamanid
• multidrug resistant tuberculosis
• treatment shortening