Abstract
The genus Mycobacterium comprises not only the deadliest of bacterial pathogens, Mycobacterium tuberculosis, but several other pathogenic species, including M. avium and M. abscessus. The incidence of infections caused by atypical or nontuberculous mycobacteria (NTM) has been steadily increasing, and is associated with a panoply of diseases, including pulmonary, soft-tissue, or disseminated infections. The treatment for NTM disease is particularly challenging, due to its long duration, to variability in bacterial susceptibility profiles, and to the lack of evidence-based guidelines. Treatment usually consists of a combination of at least three drugs taken from months to years, often leading to severe secondary effects and a high chance of relapse. Therefore, new treatment approaches are clearly needed. In this review, we identify the main limitations of current treatments and discuss different alternatives that have been put forward in recent years, with an emphasis on less conventional therapeutics, such as antimicrobial peptides, bacteriophages, iron chelators, or host-directed therapies. We also review new forms of the use of old drugs, including the repurposing of non-antibacterial molecules and the incorporation of antimicrobials into ionic liquids. We aim to stimulate advancements in testing these therapies in relevant models, in order to provide clinicians and patients with useful new tools with which to treat these devastating diseases.
Highlights
The genus Mycobacterium comprises the deadliest of bacterial pathogens, Mycobacterium tuberculosis, but several other pathogenic species, including M. avium and M. abscessus
Nontuberculous mycobacteria (NTM) are bacterial species that fall within the Mycobacterium genus, but which are outside the M. tuberculosis complex or the species M. leprae [1,2]
We will cover some of the most promising, new alternatives reported in the literature, which include the repurposing of conventional drugs and the use of ionic liquids, antimicrobial peptides, bacteriophages, iron chelators, and host-directed therapies (Figure 1)
Summary
Nontuberculous mycobacteria (NTM) are bacterial species that fall within the Mycobacterium genus, but which are outside the M. tuberculosis complex or the species M. leprae [1,2]. The most relevant NTM species for human disease are the members of the M. avium complex, M. kansasii and M. xenopi (all SGM), M. abscessus complex, M. chelonae, and M. fortuitum (the last three are RGM) [3,4,5] All of these are environmental organisms, present mainly in soil and water. Species of the M. avium complex (MAC) are the most common causes of NTM infections and are mainly responsible for the observed increase in disease incidence [3,5,6,10]. Their resistance to antibiotics is growing; the treatment used today is a multidrug therapy comprising at least three antibiotics, with treatments taking from six months to years. NTM, especially RGM, are known to adhere to biomaterials, creating biofilms in medical devices, such as catheters, which may cause pathologies which are difficult to diagnose and treat [12]
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