Abstract
Multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis (MTB) remain a primary global threat to the end of tuberculosis (TB) era. Delamanid (DLM) is a nitro-dihydro-imidazooxazole derivative utilized to treat MDR-TB. DLM has distinct mechanism of action, inhibiting methoxy- and keto-mycolic acid (MA) synthesis through the F420 coenzyme mycobacteria system and generating nitrous oxide. While DLM resistance among MTB strains is uncommon, there are increasing reports in Asia and Europe, and such resistance will prolong the treatment courses of patients infected with MDR-TB. In this review, we address the antimycobacterial properties of DLM, report the global prevalence of DLM resistance, discuss the synergism of DLM with other anti-TB drugs, and evaluate the documented clinical trials to provide new insights into the clinical use of this antibiotic.
Highlights
Notwithstanding the use of potent agents in varying combination treatment regimens, Mycobacterium tuberculosis (MTB) has an independent ability to resist antitubercular drugs (Li et al, 2019)
This review aims to discuss the synergism of DLM with other antimycobacterial agents, to summarize the available evidence on DLM resistance among drug-resistant MTB isolates, and to evaluate the clinical use of this drug, in order to provide new insights into this phenomenon
Enoyl-acyl carrier protein reductase, InhA, is a specific factor for the function of INH, while DLM needs mycobacterial F420 system for its activation (Parikh et al, 2000; Deane and Porkess, 2018). This system is the analog of flavin mononucleotide complex and composed of two enzymes, deazaflavin-dependent nitroreductase (Ddn, Rv3547) and F420dependent glucose-6-phosphate dehydrogenase (G6PD; FGD1, Rv0407), as well as four coenzymes, FbiA (Rv3361), FbiB
Summary
Notwithstanding the use of potent agents in varying combination treatment regimens, Mycobacterium tuberculosis (MTB) has an independent ability to resist antitubercular drugs (Li et al, 2019). Resistance, Synergism, and Clinical Implications of Delamanid from phase IIb trial and with regard to medical need for treating MDR-TB (Blair and Scott, 2015; Khoshnood et al, 2021). The rapid acquisition of resistance by DLM highlights the demand for the proper use of such new drugs and medication, and emphasizes the significance of drug resistance surveillance. This review aims to discuss the synergism of DLM with other antimycobacterial agents, to summarize the available evidence on DLM resistance among drug-resistant MTB isolates, and to evaluate the clinical use of this drug, in order to provide new insights into this phenomenon
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