Nontuberculous Mycobacteria in Cystic Fibrosis

Abstract

Nontuberculous mycobacteria (NTM) can cause chronic pulmonary infection in susceptible hosts. Individuals with cystic fibrosis (CF), a multisystem disease predominated by progressive structural lung disease, are particularly vulnerable. Only recently have NTM been recognized for their potential to cause lung deterioration in CF patients. The reported prevalence varies widely from 4 to 40%, significantly more common than in the general population, but this varies because of multiple factors including inconsistent screening practices. complex and complex are the two most common species recovered. Defining NTM pulmonary disease in a CF patient can present challenges as it can be difficult to distinguish from the other potentially pathogenic organisms in the lung microbiome. In general, treatment regimens do not differ from the non-CF population but the clinician should be aware of potential interactions with other CF therapies. Recent population-level genomics has raised serious concern for indirect person-to-person transmission of several dominating NTM clones worldwide, raising awareness for increase prevention strategies when CF patients potentially congregate, such as clinic visits. Lung transplantation is controversial in those with NTM present in sputum culture but the available evidence suggests that this is not an absolute contraindication.

Druggable redox pathways against Mycobacterium abscessus in cystic fibrosis patient-derived airway organoids

“…Here, we have reproduced Mabs infection hallmarks in AOs in healthy and CF contexts. Specifically, we show that both S-and R-Mabs replicate as extracellular bacteria in AOs, which was further enhanced in CF context, thus recapitulating the susceptibility of CF patients to NTM infection [54,55] and consistent with Mabs localization in the airway of CF patients [56]. We showed that Mabs S is surrounded by an extracellular substance resembling a biofilm.…”

Performance of lipid fingerprint-based MALDI-ToF for the diagnosis of mycobacterial infections

“…Currently, most clinical laboratories have systems which operate in positive ion mode only. Where this is the case, a combination of inexpensive rapid antigen testing (MBT64) combined with lipidomic MALDI-ToF analysis would provide definitive TB identification (TB or not TB, and likely NTM species) rapidly and cheaply in all clinical laboratories and provide species-level identification for NTMs which can have immediate management implications in certain populations (cystic fibrosis, non-cystic fibrosis bronchiectasis, cardiothoracic surgery, immunosuppressed individuals) [ [42] , [43] , [44] , [45] , [46] ].…”

Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus

“…Mycobacterial infections impose a substantial global health burden, and drug resistance in Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) is widespread1 , 2. Cystic Fibrosis (CF) patients frequently have NTM infections, including Mycobacterium abscessus 3 , 4, which are antibiotic resistant and difficult to manage clinically3 , 5. CF is the third most common indication for lung transplantation, but persistent infection – particularly when NTM are present prior to surgery – can result in substantial post-transplant morbidity and mortality4 , 6 , 7.…”

“…Cystic Fibrosis (CF) patients frequently have NTM infections, including Mycobacterium abscessus 3 , 4, which are antibiotic resistant and difficult to manage clinically3 , 5. CF is the third most common indication for lung transplantation, but persistent infection – particularly when NTM are present prior to surgery – can result in substantial post-transplant morbidity and mortality4 , 6 , 7. Therapeutic bacteriophages are a plausible alternative treatment to antibiotics8, but have not been used for mycobacterial infections in humans9 – 11; personalized intravenous phage treatments for other bacterial infections have been described (Supplemental Information)12 , 13.…”