Novel drugs against tuberculosis: a clinician's perspective

Abstract

The United Nations Millennium Development Goal of reversing the global spread of tuberculosis by 2015 has been offset by the rampant re-emergence of drug-resistant tuberculosis, in particular fluoroquinolone-resistant multidrug-resistant and extensively drug-resistant tuberculosis. After decades of quiescence in the development of antituberculosis medications, bedaquiline and delamanid have been conditionally approved for the treatment of drug-resistant tuberculosis, while several other novel compounds (AZD5847, PA-824, SQ109 and sutezolid) have been evaluated in phase II clinical trials. Before novel drugs can find their place in the battle against drug-resistant tuberculosis, linezolid has been compassionately used with success in the treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis. This review largely discusses six novel drugs that have been evaluated in phase II and III clinical trials, with focus on the clinical evidence for efficacy and safety, potential drug interactions, and prospect for using multiple novel drugs in new regimens. @ERSpublications A review of the efficacy, safety, and potential of new drugs to improve TB therapy from the perspective of clinicians

Mefloquine as a potential drug against multidrug-resistant tuberculosis

“…Whether such a treatment regimen is effective and able to reduce toxicity so that it would enable to tolerate mefloquine for 6 months and more has to be investigated in prospective studies including clinical effectiveness and pharmacokinetics. In general, we believe that treatment periods limited to 6 months for a single drug even within a long-term combined treatment of MDR-TB should be handled with caution, because no long-term data on the development of secondary resistance exist for the two drugs proposed for 6 months treatment period (delamanid, bedaquiline) [11].…”

Disulfiram and Copper Ions Kill Mycobacterium tuberculosis in a Synergistic Manner

“…Major obstacles to global control efforts include (i) the complete lack of convenient and easy-to-comply-with short-term or single-drug treatment options, (ii) the ability of Mycobacterium tuberculosis to persist in the human host, asymptomatically and undetectably, during and after treatment with a 10% lifetime chance to reactivate eventually (2), (iii) adverse drug interactions in the cotreatment of HIV and M. tuberculosis infections (3,4), (iv) a short supply of first-line drugs (5), and (v) the rise of multidrug-resistant (MDR), extensively drug-resistant (XDR), and even totally drug-resistant (TDR) M. tuberculosis strains (6). Only two new antitubercular drugs, bedaquiline (Sirturo, TMC207) and delamanid (Deltyba, OPC-67683), were approved in recent years for use against MDR-and XDR-TB in the United States and Europe, respectively, with phase III clinical trials still ongoing to elucidate potentially serious side effects that may limit the utility of these drugs (7)(8)(9). Additional antituberculosis drugs are still desperately needed.…”

Effects of Lipid-Lowering Drugs on Vancomycin Susceptibility of Mycobacteria

“…There is growing concern to discover new drugs to fight MDR-and XDR-TB. As such, bedaquiline and delamanid have been recently approved for treating MDR-TB, and other drugs are currently in clinical trials (3,4).…”