Therapeutic and Microbiological Approaches for Combating Non-tuberculous Mycobacterial Infections

Dear Colleagues,

The incidence of non-tuberculous mycobacterial (NTM) infections is increasing in many countries, even surpassing tuberculosis (TB). Pulmonary disease (PD) is the most important clinical presentation, especially in people suffering with chronic diseases such as bronchiectasis or chronic obstructive pulmonary disease (COPD). Although more than 160 species have been described, most NTM-PD cases are caused by the Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB). The backbone of the treatment is based on regimens including macrolides. Additionally, at least three drugs are administered for 18-24 months. The current therapeutical options are limited to 4-5 drugs, such as amikacin, rifamycins, ethambutol, tigecycline, imipenem cefoxitin and linezolid. However, some cases do not respond to treatment, and relapse occurs in more than 10% of MAC and in at least 50% of MAB infections. Drug susceptibility testing (DST) shows resistance for many drugs, such as beta-lactams, tetracyclines, aminoglycosides and others. Moreover, sometimes there is a discordance between in vitro susceptible results and the clinical response and outcome. Drug resistance can be due to intrinsic factors, such as impermeability and efflux pumps, or acquired due to target mutations or other complementary causes. Drug tolerance can result in difficulties reaching the target. For example, this can be due to the intracellular environment, vascular hypoperfusion, or the hypersecretion of mucus and production of biofilm.

It is common to adapt and study TB drugs in NTM. However, they are not always active, and the activity levels can be different given that several bactericidal drugs against TB are bacteriostatic in NTM. There is an urgent need for new compounds with anti-mycobacterial activity and for the study of new combinations, including new and existing drugs. For instance, in recent years, the combination of betalactamase inhibitors with cephalosporines or carbapenems has demonstrated synergistic activity. Other strategies, such as inhaled nitric oxid (NO) or the use of specific phages, should be potentiated. Mucus and biofilm act as barriers to access the mycobacterial cells, requiring minimum inhibitory concentrations (MICs) several folds higher. The treatment should potentiate alternative routes of administration, such as inhalation and the use of compounds that dissolve mucus and biofilm, in order to help antibiotics to reach their targets.

There is also a need to find biomarkers to distinguish who should be treated, and predict the outcome, relapse and mortality as well as, in the near future, design personalized treatments according to the individual characteristics of each patient

Prof. Dr. Julia Gonzalez-Martin
Prof. Dr. Griselda Tudó
Guest Editors

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• mycobacterial infections
• non-tuberculous mycobacteria (NTM) drug resistance
• NTM treatment
• NTM epidemiology
• NTM microbiology