Management of multidrug-resistant TB: novel treatments and their expansion to low resource settings

Abstract

Despite overall progress in global TB control, the rising burden of multidrug-resistant TB (MDR-TB) threatens to undermine efforts to end the worldwide epidemic. Of the 27 countries classified as high burden for MDR-TB, 17 are in ‘low’ or ‘low–middle’ income countries. Shorter, all oral and less toxic multidrug combinations are required to improve treatment outcomes in these settings. Suitability for safe co-administration with HIV drugs is also desirable. A range of strategies and several new drugs (including bedaquiline, delamanid and linezolid) are currently undergoing advanced clinical evaluations to define their roles in achieving these aims. However, several clinical questions and logistical challenges need to be overcome before these new MDR-TB treatments fulfil their potential.

Prevalence of drug-resistant pulmonary tuberculosis in India: systematic review and meta-analysis

“…Accelerated tuberculosis (TB) control efforts have been threatened by the emergence of Mycobacterium tuberculosis strains that are resistant to potent first-line drugs (drug resistant tuberculosis or DR-TB) [1–3]. In 2015, the World Health Organization (WHO) estimated 480,000 incident multidrug resistant TB (MDR-TB; resistance of both isoniazid and rifampicin) cases globally.…”

Avances en el tratamiento de la tuberculosis multirresistente

“…estos esquemas han sido utilizados para el rescate de pacientes con tBC-MDr en sudáfrica, asociando bedaquilina, linezolid y protiomanid durante 4 a 6 meses. también se está ensayando en la tBC sensible para reducir el tiempo de tratamiento 21 .…”

Delamanid and its Role in Drug-Resistant Tuberculosis

“…Thus, need for shorter and more effective treatment regimens is urgent. [7,8,9] After a gap of nearly 50 years, new classes of tuberculosis antibiotics are under development. [2] Delamanid, previously named OPC-67683, a Nitro-dihydroimidazo-oxazole, is undergoing commercial development.…”

“…[2] Delamanid, previously named OPC-67683, a Nitro-dihydroimidazo-oxazole, is undergoing commercial development. [2,8,9] It is a new agent which prevents mycolic acid synthesis, has shown potent in vitro and in vivo activity against both drug-susceptible and drug-resistant strains of M. tuberculosis in preclinical development. [10] A Phase IIb randomised controlled trial in adults with pulmonary MDR-TB, showed improved rates of sputum culture conversion at 2 months when an OBR was augmented with delamanid as compared to placebo .…”

“…An openlabel extension of this trial found that patients who consumed Delamanid for 2-6 months had more positive outcomes (cured or completed treatment) and lower mortality than those who took delamanid for ≤2 months. [9] It has been included in the World Health Organization (WHO) Model List of Essential Medicine by the WHO Expert Committee on Selection and Use of Essential Medicines. [7] Japanese researchers who are investigating the properties of the nitro-dihydro-imidazooxazoles, found that Delamanid had superior activity against MTB than other closely related compounds.…”