Mycobacterial lung disease in cystic fibrosis: a prospective study

Fauroux, Brigitte; Delaisi, Bertrand; Clément, Annick; Saizou, Carole; Moissenet, Didier; Truffot-Pernot, C.; Tournier, G; Thien, H. Vu

doi:10.1097/00006454-199704000-00004

Cited by 121 publications

(74 citation statements)

References 15 publications

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“…There is general consensus that, in CF and non-CF populations, M. abscessus is a more virulent bacteria than MAC (13,17,28,29,36), that it may be associated with a greater rate of FEV 1 decline (7,30), and that it is more difficult to treat (17,26,37). However, our results demonstrate that both MAC and M. abscessus can be cleared spontaneously in a subset of patients with CF or can result in an apparently indolent infection.…”

Section: Original Researchmentioning

confidence: 55%

“…Although much has been learned concerning the epidemiology of NTM in CF, previous studies examining the prevalence of NTM and potential risk factors for acquisition were not designed to guide clinical decision-making. Several additional reports have prospectively or retrospectively analyzed the impact of NTM on progression of CF lung disease (7,8,13,16,(26)(27)(28). However, even in multicenter trials, cases are relatively rare, and distinguishing between patients with a single positive culture, patients with apparent indolent infection, and patients with NTM disease is difficult from reviewing databases in the absence of a detailed history and extended clinical follow-up (28); thus, data from these different populations may be combined (8,16,27).…”

Section: Discussionmentioning

confidence: 99%

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Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

et al. 2014

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Rationale: Little is known about outcomes of infection with nontuberculous mycobacteria (NTM) in cystic fibrosis (CF) or about the significance of a positive NTM culture. Determining which patients are at risk for active NTM disease is clinically valuable.Objectives: To examine the clinical course of subjects with CF with an initial positive NTM culture and identify characteristics associated with active NTM disease.Methods: We performed a retrospective study of pediatric and adult subjects with CF with at least one positive NTM culture at the Colorado CF Center from 2000 to 2010.Measurements and Main Results: Mycobacterium avium complex was the first identified NTM in the majority of subjects (73%). The frequency of growing a second NTM species was 26% at 5 years. Clinical characteristics and distribution of NTM species between pediatric and adult subjects were similar except for differences in baseline FEV 1 (89% vs. 71%; P , 0.001) and coinfection with Pseudomonas aeruginosa (33% vs. 55%; P = 0.04). Over 60% of subjects had transient or persistent infection but not active NTM disease. Subjects who developed active NTM disease were distinguished from those with transient or persistent infection, respectively, by FEV 1 at the time of first positive NTM culture (72% vs. 84 or 86%; P = 0.02) and FEV 1 decline in the prior year (25.8%/yr vs. 20.7%/yr [P = 0.009] or 20.4%/yr [P = 0.001]). Conclusions:The majority of patients with CF with a first positive NTM culture do not progress to active disease. Lower lung function and accelerated lung function decline appear to be indicators of the significance of an initial positive NTM culture.

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Section: Original Researchmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

et al. 2014

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“…It is also a pulmonary pathogen in patients with cystic fibrosis (Cullen et al, 2000;Fauroux et al, 1997;Olivier et al, 2003;Sermet-Gaudelus et al, 2003). In some instances, isolation of M. abscessus from the sputum is not associated with progressive lung infection and may be the result of transient airway colonization (Griffith et al, 2007;Jönsson et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Deletion of the mmpL4b gene in the Mycobacterium abscessus glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response

et al. 2011

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Mycobacterium abscessus is considered to be the most virulent of the rapidly growing mycobacteria. Generation of bacterial gene knockout mutants has been a useful tool for studying factors that contribute to virulence of pathogenic bacteria. Until recently, the optimal genetic approach to generation of M. abscessus gene knockout mutants was not clear. Based on the recent identification of genetic recombineering as the preferred approach, a M. abscessus mutant was generated in which the gene mmpL4b, critical to glycopeptidolipid synthesis, was deleted. Compared to the previously well-characterized parental strain 390S, the mmpL4B deletion mutant had lost sliding motility and the ability to form biofilm, but acquired the ability to replicate in human macrophages and stimulate macrophage Toll-like receptor 2. This study demonstrates that deletion of a gene associated with expression of a cell-wall lipid can result in acquisition of an immunostimulatory, invasive bacterial phenotype and has important implications for the study of M. abscessus pathogenesis at the cellular level.

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“…Recently, there has been increasing concern about the potential pulmonary pathogenicity of NTM in CF [2]. At least 12 single-site studies described a total population of ,1,300 CF patients, with an NTM prevalence varying 2-28% [3][4][5][6][7][8][9].A USA multicentre study of 986 CF patients aged .10 yrs showed a 13% NTM prevalence [10], and 16% of these had Mycobacterium abscessus (previously M. chelonae, subspecies abscessus). Although the clinical course appeared relatively benign [11], an editorial comment [12] emphasised that all NTM isolates were considered together as potential pathogens, and the majority were M. avium complex.…”

mentioning

confidence: 99%

Nontuberculous mycobacteria in cystic fibrosis associated with allergic bronchopulmonary aspergillosis and steroid therapy

Mussaffi¹

2005

Eur Respir J

111

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Nontuberculous mycobacterial (NTM) infection, particularly due to Mycobacterium abscessus, is an emerging disease that can be relentlessly progressive, particularly in cystic fibrosis (CF) patients. The risk factors that were associated with this increasingly symptomatic infection in a group of CF patients were investigated.A total of 139 CF patients aged 2-52 yrs were reviewed. Sputum was cultured for NTM annually or whenever clinical deterioration was unexplained.In total, 12 patients (8.6%) had positive cultures and six (4.3%) met the criteria for NTM pulmonary disease (five with M. abscessus). Five had allergic bronchopulmonary aspergillosis (ABPA) compared with one out of 133 patients without NTM disease. Five had received systemic steroids (four as a treatment for ABPA) compared with only one out of 133 without NTM lung disease. All six NTM patients deteriorated markedly following mycobacterial infection, and forced expiratory volume in one second dropped 18-46%. Despite prolonged triple antibiotic therapy, M. abscessus was not eradicated, and four out of six did not return to baseline clinically.In conclusion, severe nontuberculous mycobacterial lung disease, particularly with Mycobacterium abscessus, is becoming a perplexing challenge in cystic fibrosis patients. Allergic bronchopulmonary aspergillosis and systemic steroids appear to be risk factors, although small patient numbers limit this to a descriptive observation. When pulmonary condition deteriorates, increased surveillance for mycobacteria would enable prompt diagnosis and treatment.KEYWORDS: Allergic bronchopulmonary aspergillosis, cystic fibrosis, Mycobacterium abscessus, nontuberculous mycobacteria, pulmonary infection, steroid therapy L ife expectancy and quality of life have been improving steadily in cystic fibrosis (CF), as treatment regimens become more aggressive. Concomitantly, reports describe the rising incidence of unusual pulmonary pathogens in CF, including Stenotrophomonas maltophilia, Alkaligenes xyloxidans, Nocardia and nontuberculous mycobacteria (NTM) [1]. Recently, there has been increasing concern about the potential pulmonary pathogenicity of NTM in CF [2]. At least 12 single-site studies described a total population of ,1,300 CF patients, with an NTM prevalence varying 2-28% [3][4][5][6][7][8][9].A USA multicentre study of 986 CF patients aged .10 yrs showed a 13% NTM prevalence [10], and 16% of these had Mycobacterium abscessus (previously M. chelonae, subspecies abscessus). Although the clinical course appeared relatively benign [11], an editorial comment [12] emphasised that all NTM isolates were considered together as potential pathogens, and the majority were M. avium complex. Focusing on more virulent pathogens, such as M. abscessus, might accentuate important differences in prognosis, but small numbers probably precluded this. In contrast, a French study [7] described M. abscessus as the most prevalent NTM by far, particularly in younger CF patients.Recently, the current authors have encountered CF patien...

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Mycobacterial lung disease in cystic fibrosis: a prospective study

Abstract: We recommend performing AFB smears and cultures in CF children with severe lung disease and/or during a lung exacerbation. In these patients persistence of M. chelonae or M. abscessus in sputum should lead to consideration of treatment with clarithromycin.

Cited by 121 publications

References 15 publications

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

Clinical Significance of a First Positive Nontuberculous Mycobacteria Culture in Cystic Fibrosis

Deletion of the mmpL4b gene in the Mycobacterium abscessus glycopeptidolipid biosynthetic pathway results in loss of surface colonization capability, but enhanced ability to replicate in human macrophages and stimulate their innate immune response

Nontuberculous mycobacteria in cystic fibrosis associated with allergic bronchopulmonary aspergillosis and steroid therapy

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