Novel Treatments for Drug-Resistant Tuberculosis

Abstract

Drug resistance has emerged as a major obstacle to global control of tuberculosis (TB). Treatment with currently available medications requires prolonged courses of numerous drugs, many of which are associated with significant adverse effects. New drugs are urgently needed to meet the challenge posed by drug-resistant TB, in order to relieve the burden that drug resistance has placed on individual patients and health systems. Fortunately, many new drugs have been developed for the treatment of drug-resistant TB in recent years. The new antimycobacterial agents are derived from various medication classes, work by means of an assortment of mechanisms of action, and are at differing phases of development. This review provides a survey of the most promising new agents, in order to promote familiarity with these emerging drugs and compounds.

Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010–2020 Review

“…Moreover, in the continuation phase of a murine TB model, Jia et al (2006) documented that PD maintained potent MIC values of 0.15–0.3 µg/mL and that these data are comparable to the activity of a combination regimen with isoniazid and rifampicin [ 104 ]. More intriguing results came from studies investigating PD as part of a novel TB regimen called PaMZ, comprising of PD, MFX, and pyrazinamide [ 105 ]. A comparative phase II trial study among patients with both MDR-TB and DS-TB, given PaMZ at 200 mg, showed superior bactericidal activity over standard therapy [ 106 ].…”

“…As with BDQ and DM, PD has been associated with QT interval prolongation [ 105 ]. A number of other adverse events have been reported in phase III trials which include peripheral neuropathy and anemia [ 112 ].…”

“…Having completed phase IIa trials and is likely to be advanced to the next phases, AZD-5847 is likely to be the third oxazolidinone repurposed as an anti-TB agent [ 138 ]. Despite showing the same mechanism of action as SZD and LZD, AZD-5847 demonstrated superior in vitro bactericidal activity against Mtb compared to that of LZD and has retained activity against MDR and XDR strains [ 105 ]. Moreover, AZD-5847 has additive activity when used in combination with other anti-TB drugs [ 139 ].…”

Pharmacotherapy Approaches in Nontuberculous Mycobacteria Infections

“…Bedaquiline is a newer diarylquinoline antimycobacterial agent that has been used for drug-resistant tuberculosis, but it also may be considered in salvage therapy for difficultto-treat NTM infections. 72 Although modest, some therapeutic benefits have been shown in patients with refractory MAC and M abscessus complex disease when bedaquiline was used. 73 Bedaquiline should be taken with food to increase bioavailability.…”

Metabolomics of colistin methanesulfonate treated Mycobacterium tuberculosis

“…Currently, the WHO approved treatment approach entails a 6 months combination treatment approach which is called the "directly observed treatment short-course" (DOTS) regimen [3]. According to the annual WHO report, a significant improvement to current treatment strategies is going to be a challenge, however the identification of new anti-TB drug candidates and or alternative treatment regimens, might be a plausible option for speeding up treatment duration and subsequently lowering the TB prevalence globally [4,5]. Although there are currently a number of new potential anti-TB drugs undergoing phase II and III preclinical trials, delamanid and bedaquiline are the only two new anti-TB drugs to have been approved over the last 50 years.…”