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      Shifting paradigms of nontuberculous mycobacteria in cystic fibrosis

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          Abstract

          Important paradigms of pulmonary disease with nontuberculous mycobacteria (NTM) are currently shifting based on an increasing attention within the field of cystic fibrosis (CF). These shifts are likely to benefit the management of all patients with pulmonary NTM, regardless of underlying pathology. Currently several key areas are being revised: The first outbreak of human NTM transmission has been proven and new evidence of biofilm growth in vivo has been demonstrated. A better understanding of the clinical impact of NTM infection has led to increased diagnostic vigilance and new recommendations for lung transplantation are under way. While recent changes have reinvigorated the interest in NTM disease, the challenge remains, whether such advances can be successfully translated into improved management and care.

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          Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients.

          Thomas Bjarnsholt, Peter Østrup Jensen, Mark J. Fiandaca … (2009)
          The present study was undertaken to investigate the appearance and location of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung and in sputum. Samples include preserved tissues of CF patients who died due to chronic P. aeruginosa lung infection prior to the advent of intensive antibiotic therapy, explanted lungs from 3 intensively treated chronically P. aeruginosa infected CF patients and routine sputum from 77 chronically P. aeruginosa infected CF patients. All samples were investigated microscopically using hematoxylin-eosin (HE), Gram and alcian-blue stain, PNA FISH and immunofluorescence for alginate.Investigation of the preserved tissues revealed that prior to aggressive antibiotic therapy, P. aeruginosa infection and destruction of the CF lung correlated with the occurrence of mucoid (alginate) bacteria present in aggregating structures surrounded by pronounced polymorphonuclear-leukocyte (PMN) inflammation in the respiratory zone (9/9). Non-mucoid bacteria were not observed here, and rarely in the conductive zone (1/9). However, in the explanted lungs, the P. aeruginosa aggregates were also mucoid but in contrast to the autopsies, they were very rare in the respiratory zone but abundant in the sputum of the conductive zone (3/3), which also contained abundances of PMNs (3/3). Non-mucoid and planktonic P. aeruginosa were also observed here (3/3).In conclusion, the present intensive antibiotic therapy of chronic P. aeruginosa infections, at the Copenhagen CF Centre, seems to restrain but not eradicate the bacteria from the conductive zone, whereas the remaining healthy respiratory zone appears to be protected, for a long period, from massive biofilm infection. This strongly suggests that the conductive zone serves as a bacterial reservoir where the bacteria are organized in mucoid biofilms within the mucus, protected against antibiotics and host defenses.
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            Opportunistic pathogens enriched in showerhead biofilms.

            L. M. Feazel, L. Baumgartner, K L Peterson … (2009)
            The environments we humans encounter daily are sources of exposure to diverse microbial communities, some of potential concern to human health. In this study, we used culture-independent technology to investigate the microbial composition of biofilms inside showerheads as ecological assemblages in the human indoor environment. Showers are an important interface for human interaction with microbes through inhalation of aerosols, and showerhead waters have been implicated in disease. Although opportunistic pathogens commonly are cultured from shower facilities, there is little knowledge of either their prevalence or the nature of other microorganisms that may be delivered during shower usage. To determine the composition of showerhead biofilms and waters, we analyzed rRNA gene sequences from 45 showerhead sites around the United States. We find that variable and complex, but specific, microbial assemblages occur inside showerheads. Particularly striking was the finding that sequences representative of non-tuberculous mycobacteria (NTM) and other opportunistic human pathogens are enriched to high levels in many showerhead biofilms, >100-fold above background water contents. We conclude that showerheads may present a significant potential exposure to aerosolized microbes, including documented opportunistic pathogens. The health risk associated with showerhead microbiota needs investigation in persons with compromised immune or pulmonary systems.
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              Chronic Mycobacterium abscessus infection and lung function decline in cystic fibrosis.

              Charles Esther, Denise A Esserman, Peter Gilligan … (2010)
              Although nontuberculous mycobacteria (NTM) are recognized pathogens in cystic fibrosis (CF), associations with clinical outcomes remain unclear. Microbiological data was obtained from 1216 CF patients over 8years (481+/-55patients/year). Relationships to clinical outcomes were examined in the subset (n=271, 203+/-23 patients/year) with longitudinal data. Five hundred thirty-six of 4862 (11%) acid-fast bacilli (AFB) cultures grew NTM, with Mycobacterium abscessus (n=298, 55.6%) and Mycobacterium avium complex (n=190, 35.4%) most common. Associated bacterial cultures grew Stenotrophomonas or Aspergillus species more often when NTM were isolated (18.2% vs. 8.4% and 13.9% vs. 7.2%, respectively, p<0.01). After controlling for confounders, patients with chronic M. abscessus infection had greater rates of lung function decline than those with no NTM infection (-2.52 vs. -1.64% predicted FEV(1)/year, p<0.05). NTM infection is common in CF and associated with particular pathogens. Chronic M. abscessus infection is associated with increased lung function decline. Copyright (c) 2009 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Tavs Qvist
                Tania Pressler
                Niels Høiby
                Terese L Katzenstein
                Journal
                Journal ID (nlm-ta): Respir Res
                Journal ID (iso-abbrev): Respir. Res
                Title: Respiratory Research
                Publisher: BioMed Central
                ISSN (Print): 1465-9921
                ISSN (Electronic): 1465-993X
                Publication date (Print): 2014
                Publication date (Electronic): 11 April 2014
                Volume: 15
                Issue: 1
                Page: 41
                Affiliations
                [1 ]Department of Infectious Diseases, Cystic Fibrosis Center Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
                [2 ]Department of Clinical Microbiology, University Hospital Rigshospitalet, Copenhagen, Denmark
                Article
                Publisher ID: 1465-9921-15-41
                DOI: 10.1186/1465-9921-15-41
                PMC ID: 3986433
                PubMed ID: 24725650
                SO-VID: fb1b13ef-4144-4dfb-86e3-6e9777b4623e
                Copyright © Copyright © 2014 Qvist et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 1 November 2013
                Date accepted : 4 April 2014
                Categories
                Subject: Commentary

                ScienceOpen disciplines: Respiratory medicine
                Keywords: ntm,nontuberculous mycobacteria,cystic fibrosis,mabsc,mac,mycobacterium,abcessus,avium,massiliense,environmental mycobacteria,mott,biofilm,transmission,lung transplantation
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: ntm, nontuberculous mycobacteria, cystic fibrosis, mabsc, mac, mycobacterium, abcessus, avium, massiliense, environmental mycobacteria, mott, biofilm, transmission, lung transplantation

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