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Background: The treatment of non-tuberculous mycobacterial (NTM) infections is challenging because of the difficulty in obtaining phenotypic (pDST) and/or molecular (mDST) drug susceptibility testing and the need of a multi-drug regimen. Objectives: The objective was to describe the in vitro susceptibility patterns of various NTM species through an analysis of susceptibility results obtained on isolates collected between 2018 and 2023. Methods: Species identification and mutations in rrs or rrl genes (mDST) were identified by a line probe assay, while the pDST was performed by broth microdilution and interpreted according to CLSI criteria. Results: We analysed 337 isolates of NTM belonging to 15 species/subspecies. The Mycobacterium avium complex (MAC) was the most common (62%); other species identified included M. gordonae (11%), M. kansasii (5%), the M. abscessus complex (8%), M. chelonae (6%), and M. fortuitum (2%). The results of pDST (claritromycin and amikacin) and mDST (rrl and rrs genes) on 66 NTM strains showed that while wild-type rrl and rrs occurred in 86.3% and 94% strains, respectively, the pDST showed 88% sensitivity for clarithromycin and 57.5% for amikacin. The main incongruity was observed for macrolides. Conclusions: Most NTM are likely to be susceptible to macrolides and aminoglycosides. The molecular identification of resistant genotypes is accurate and strongly recommended for optimal patient management. [ABSTRACT FROM AUTHOR]

Background: Identifying stage-specific antigens is essential for developing tuberculosis (TB) diagnostics and vaccines. In a low TB endemic country, we characterized, the Mycobacterium tuberculosis (Mtb)-specific immune response to a pool of Mtb-derived epitopes (ATB116), demonstrated as associated with TB disease., Methods: In this prospective observational cross-sectional study, we enrolled healthy donors (HD), subjects with TB disease, and TB infection (TBI) at baseline and therapy completion. T-cell response after whole blood stimulation with the peptide pools was characterized by ELISA, flow cytometry, and multiplex assay., Results: ATB116-specific IFN-γ response (by ELISA) significantly associates with Mtb regardless of infection/disease (p<0.0001) and decreases during TB therapy (p=0.0002). Flow cytometry confirms that ATB116-specific CD4 + T-cell response associated with Mtb regardless of infection/disease (p<0.0001) and shows a significantly higher frequency of IFN-γ/IL-2 and central memory T-cells in TBI compared to TB (p=0.016; p=0.0242, respectively). CD4 + T cell-specific response decreases after TB therapy completion. The antigen-specific CD8 + T-cell response mirrors the CD4 + response. Finally, the multiplex assay analysis showed that ATB116 induces several immune factors in both TB and TBI., Conclusion: We characterized the immune response to Mtb peptide pools that is modulated by TB therapy. These results are important for our understanding of TB immunopathogenesis and vaccine design., Data Availability Statement: The raw data generated and/or analyzed within the present study will be available in INMI institutional repository (rawdata.inmi.it), subject to registration. The data can be found by selecting the article of interest from a list of articles ordered by year of publication. No charge for granting access to data is required. In the event of a malfunction of the application, the request can be sent directly by e-mail to biblioteca@inmi.it., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of Interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)