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      Incorporating direct molecular diagnostics in management algorithms for nontuberculous mycobacteria: Is it high time?

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          Highlights

          • Novel techniques are encouraged to identify nontuberculosis mycobacteria (NTM).

          • An algorithm incorporating direct molecular identification of NTM is suggested.

          • Rapid NTM identification can assist in decision-making and prompt treatment initiation.

          Abstract

          Nontuberculous mycobacteria (NTM) are a group of acid-fast mycobacteria other than Mycobacterium tuberculosis complex (MTBC) that cause pulmonary disease that is similar to the disease caused by MTBC. International guidelines for the diagnosis of pulmonary NTM disease are rigid and have remained unchanged for nearly 2 decades. In this opinion piece, we provide a new perspective on the traditional criteria by suggesting a diagnostic algorithm that incorporates direct molecular identification of NTM performed on raw sputum specimens (using Sanger or targeted deep sequencing approaches, among others) paired with traditional culture methods. Our approach ensures a more rapid diagnosis of pulmonary NTM disease, thus, facilitating timeous clinical diagnosis, and prompt treatment initiation, where indicated, and leverages recent advances in novel molecular techniques into routine NTM identification practice.

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          Most cited references40

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          Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline

          Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii , and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.
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            How to: identify non-tuberculous Mycobacterium species using MALDI-TOF mass spectrometry

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              Whole genome sequencing Mycobacterium tuberculosis directly from sputum identifies more genetic diversity than sequencing from culture

              Background Repeated culture reduces within-sample Mycobacterium tuberculosis genetic diversity due to selection of clones suited to growth in culture and/or random loss of lineages, but it is not known to what extent omitting the culture step altogether alters genetic diversity. We compared M. tuberculosis whole genome sequences generated from 33 paired clinical samples using two methods. In one method DNA was extracted directly from sputum then enriched with custom-designed SureSelect (Agilent) oligonucleotide baits and in the other it was extracted from mycobacterial growth indicator tube (MGIT) culture. Results DNA directly sequenced from sputum showed significantly more within-sample diversity than that from MGIT culture (median 5.0 vs 4.5 heterozygous alleles per sample, p = 0.04). Resistance associated variants present as HAs occurred in four patients, and in two cases may provide a genotypic explanation for phenotypic resistance. Conclusions Culture-free M. tuberculosis whole genome sequencing detects more within-sample diversity than a leading culture-based method and may allow detection of mycobacteria that are not actively replicating. Electronic supplementary material The online version of this article (10.1186/s12864-019-5782-2) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                IJID Reg
                IJID Reg
                IJID Regions
                Elsevier
                2772-7076
                13 December 2023
                March 2024
                13 December 2023
                : 10
                : 140-145
                Affiliations
                [1 ]National Health Laboratory Service, Green Point TB Laboratory, Cape Town, South Africa
                [2 ]SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South Africa
                [3 ]Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa
                [4 ]Division of Medical Microbiology, Institute of Infectious Disease and Molecular Medicine and Wellcome Centre for Infectious Disease Research, University of Cape Town, Cape Town, South Africa
                [5 ]UCT Lung Institute, Centre for Lung Infection and Immunity, Division of Pulmonology, Department of Medicine, University of Cape Town, & Groote Schuur Hospital
                Author notes
                Article
                S2772-7076(23)00130-3
                10.1016/j.ijregi.2023.12.003
                10831244
                38304760
                13df9d15-b7f4-4214-8829-0b4dd137e54a
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 14 June 2023
                : 11 December 2023
                : 11 December 2023
                Categories
                Perspective

                nontuberculous mycobacterium,mycobacteria-other-than-tuberculosis,molecular technique,guideline,pulmonary,culture

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