Of tuberculosis and non-tuberculous mycobacterial infections – a comparative analysis of epidemiology, diagnosis and treatment

Abstract

Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), recent epidemiological studies have shown the emergence of non-tuberculous mycobacteria (NTM) species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus, have been implicated in pulmonary disease. While TB is transmitted through inhalation of aerosol droplets containing Mtb, generated by patients with symptomatic disease, NTM disease is mostly disseminated through aerosols originated from the environment. However, following inhalation, both Mtb and NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mtb and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. The diagnostic modalities for TB, including molecular diagnosis and drug-susceptibility testing (DST), are more advanced and possess a higher rate of sensitivity and specificity, compared to the tools available for NTM infections. In general, drugsensitive TB is effectively treated with a standard multi-drug regimen containing well-defined first-and second-line antibiotics. However, the treatment of drug-resistant TB requires the additional, newer class of antibiotics in combination with or without the first and second-line drugs. In contrast, the NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs. Thus, the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides. Although well-established international guidelines are available, treatment of NTM disease is mostly empirical and not entirely

Opportunist Coinfections by Nontuberculous Mycobacteria and Fungi in Immunocompromised Patients

“…Sputum-conversion, from a positive to negative finding of bacteria, is often difficult to achieve in NTM cases, especially for infection with macrolide-resistant NTM spp. [161]. Despite the existence of specific guidelines, based on the nature of infecting mycobacteria and requiring spp.…”

“…Despite the existence of specific guidelines, based on the nature of infecting mycobacteria and requiring spp. identification, treatment of NTM disease is mostly empirical and not entirely successful [161]. The treatment of NTM diseases usually involves the use of macrolides and injectable aminoglycosides.…”

“…Drug susceptibility tests (DSTs) for NTM are challenging and controversial because of inconsistency between in vitro results and clinical outcomes [161]. Macrolides are an exception exhibiting a good correlation between in vitro susceptibility results and clinical response.…”

“…The treatment of M. abscessus lung disease faces significant challenges due to intrinsic antibiotic resistance [164], oral macrolides combined with two parenteral drugs being the medication of choice [161]. M. massiliense, one of the three subspecies of MABC, harbors a partial erm41 gene deletion preventing inducible macrolide resistance and leading to higher rates of successful treatment with macrolide-based antibiotic regimens compared to infections by M. abscessus (functional erm41 gene) [166,167].…”

“…Antimicrobial peptides exhibit a broad-spectrum of antimicrobial activity against bacteria, viruses, parasites and fungi, and could be alternatives for the treatment of mycobacterial infections [192]. Other alternatives include a phage therapy with the use of bacteriophages [193] and host-directed therapies (HDT), which might improve the clinical outcome of NTM therapy and/or reduce the duration of treatment [161]. Natural approaches are also gaining consideration in overcoming antimicrobial resistance in NTMs, especially compounds from plants and venoms [194].…”