New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid

Abstract

The current treatment for drug-resistant tuberculosis (TB) is long, complex, and associated with severe and life-threatening side effects and poor outcomes. For the first time in nearly 50 years, there have been two new drugs registered for use in multidrug-resistant TB (MDR-TB). Bedaquiline, a diarylquinoline, and delamanid, a nitromidoxazole, have received conditional stringent regulatory approval and have World Health Organization interim policy guidance for their use. As countries improve and scale up their diagnostic services, increasing number of patients with MDR-TB and extensively drug-resistant TB are identified. These two new drugs offer a real opportunity to improve the outcomes of these patients. This article reviews the evidence for these two new drugs and discusses the clinical questions raised as they are used outside clinical trial settings. It also reviews the importance of the accompanying drugs used with these new drugs. It is important that barriers hindering the use of these two new drugs are addressed and that the existing clinical experience in using these drugs is shared, such that their routine-use programmatic conditions is scaled up, ensuring maximum benefit for patients and countries battling the MDR-TB crisis.

Preliminary Evaluation of Artemisinin–Cholesterol Conjugates as Potential Drugs for the Treatment of Intractable Forms of Malaria and Tuberculosis

“…[10] The spread of theses trains hamper progress made thus far to combatT B. Although newer drugs such as bedaquiline and delamanid have received conditional approval for use in the treatment of MDR-TB, [11] toxicity concerns are as yet unresolved and combination therapies are not yet available. [11,12] Overall,n ew TB drugs are urgently needed in order to eradicate these strains.…”

Proposal for a standardised treatment regimen to manage pre- and extensively drug-resistant tuberculosis cases

“…2) Bedaquiline. This is also a potentially core drug with bactericidal and sterilising characteristics [18,19,[26][27][28][29][30]. Some countries may value the use of delamanid instead of bedaquiline, as it also has the features of a core drug [19,28,31,32].…”

Delamanid and its Role in Drug-Resistant Tuberculosis

“…[7] It is hoped that these new drugs will improve the treatment of drug-resistant forms of TB, in terms of both better outcomes and quality of life for patients. [11] Mechanism of action Delamanid is a Dihydro-nitroimidazooxazole derivative. It is a pro-drug which gets activated by the enzyme deazaflavin dependent nitroreductase (Rv3547).…”