N o n t u b e rc u l o u s Mycobacterial Infections i n C y s t i c F i b ro s i s Stacey L. Martiniano, MDa, Jerry A. Nick, MDb,c, Charles L. Daley, MDb,c,* KEYWORDS Cystic fibrosis Nontuberculous mycobacteria Mycobacterium avium complex Mycobacterium abscessus complex
KEY POINTS
INTRODUCTION
EPIDEMIOLOGY
Nontuberculous mycobacteria (NTM) have emerged as important pathogens in the setting of cystic fibrosis (CF) lung disease. Although historically CF has been considered a fatal disease of childhood, improvements in therapy have resulted in the oldest and healthiest CF population in history. However, as the disease phenotype has changed in response to improved treatment, it appears that susceptibility to NTM has increased.1–3 This article reviews the epidemiology, diagnosis, treatment, and prevention of NTM lung disease in people living with CF.
The CF population has an especially high risk for NTM infection and poses unique challenges with regard to diagnosis, treatment, and prevention.4 Although the NTM isolation rate in the general population in North America ranges from approximately 6 to 22 per 100,000 and the NTM disease rate from 5 to 10 per 100,000,5 there is a 1000fold greater prevalence of NTM in respiratory cultures from patients with CF. The reported prevalence of positive NTM cultures and/or NTM disease within various CF patient cohorts or at single centers varies dramatically,6,7 but in the
Disclosures: The authors are supported by the Cystic Fibrosis Foundation Research Development Grant (NICK15R0). a Department of Pediatrics, Children’s Hospital Colorado, University of Colorado Denver School of Medicine, 13123 East 16th Avenue, Box B-395, Aurora, CO 80045, USA; b Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA; c Department of Medicine, University of Colorado Anschutz Medical Campus, 13001 E. 17th Place, Aurora, CO 80045, USA * Corresponding author. Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206. E-mail address: [email protected] Clin Chest Med 37 (2016) 83–96 http://dx.doi.org/10.1016/j.ccm.2015.11.001 0272-5231/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
chestmed.theclinics.com
Nontuberculous mycobacterial (NTM) lung infections appear to be increasing in patients with cystic fibrosis (CF). Mycobacterium avium complex and Mycobacterium abscessus complex are the most frequently encountered NTM respiratory pathogens in patients with CF in most areas. Diagnosis of NTM lung disease in patients with CF generally follows American Thoracic Society and Cystic Fibrosis Foundation guidelines, with an emphasis on evaluating and treating all known comorbidities. Therapy for NTM in patients with CF depends on the species, resistance pattern, and extent of disease. Optimal management of patients with CF and NTM lung disease requires carefully considered treatment of both conditions.
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Martiniano et al largest studies the overall prevalence is 6% to 13%.1,3,8–12 In a recent review of data from the US CF Patient Registry, the median state prevalence of NTM in patients with CF was 12%, although this ranged from 0% to 28% (Fig. 1). Significant spacial clustering of NTM was detected in Wisconsin, Arizona, Florida, and Maryland.13 The prevalence of NTM infection appears to be increasing within the CF population,1–3,9,14–17 as it is in the general population.18,19 For example, among patients with CF in Israel, NTM infection prevalence increased threefold from 5% in 2003% to 14.5% in 2011.16 The reasons for the increase in prevalence are uncertain but culture techniques, increased physician awareness, and more frequent diagnosis of “nonclassic” forms of CF in adulthood may contribute to the apparent increase in NTM prevalence observed in this population.14 Most NTM species recovered in CF samples in the United States are from either the Mycobacterium avium complex (MAC) or the Mycobacterium abscessus complex (MABSC).12 MAC has historically been the most common NTM isolated from respiratory specimens,20–23 and in the largest US survey it was present in up to 72% of patients with NTM-positive sputum cultures.9 Among patients with CF in the US Patient Registry during 2010 to 2011, 60% of positive cultures were for
MAC, although this ranged by state, from 29% in Louisiana to 100% in Nebraska and Delaware.12 The percentage of MABSC reported in patients with CF with NTM-positive sputum cultures has ranged between 16% and 68%,3,8,9,24 and it appears that the proportion of MABSC is increasing,1,2,25 with some centers reporting a greater frequency than MAC. In part, this variation may be due to geographic factors, as MABSC appears especially prevalent in Europe,3,8,24,25 and Mycobacterium simiae and MABSC are the most common species isolated in Israel.16,26 Differences in relative prevalence of MAC and MABSC may also relate to the age of the cohorts studied, as MAC is more often associated with older patients with CF, often diagnosed in adulthood, whereas MABSC is frequently seen in younger patients and those with more severe lung disease.3,27 Less frequently isolated species include Mycobacterium kansasii7,8,21,23 and Mycobacterium fortuitum.8,22,28,29
Individual Risk Factors for Nontuberculous Mycobacteria in Cystic Fibrosis Our understanding of individual risk factors for NTM in patients with CF is incomplete, as most reports have studied relatively small cohorts from
Fig. 1. State-level prevalence and significant (P
KEY POINTS
INTRODUCTION
EPIDEMIOLOGY
Nontuberculous mycobacteria (NTM) have emerged as important pathogens in the setting of cystic fibrosis (CF) lung disease. Although historically CF has been considered a fatal disease of childhood, improvements in therapy have resulted in the oldest and healthiest CF population in history. However, as the disease phenotype has changed in response to improved treatment, it appears that susceptibility to NTM has increased.1–3 This article reviews the epidemiology, diagnosis, treatment, and prevention of NTM lung disease in people living with CF.
The CF population has an especially high risk for NTM infection and poses unique challenges with regard to diagnosis, treatment, and prevention.4 Although the NTM isolation rate in the general population in North America ranges from approximately 6 to 22 per 100,000 and the NTM disease rate from 5 to 10 per 100,000,5 there is a 1000fold greater prevalence of NTM in respiratory cultures from patients with CF. The reported prevalence of positive NTM cultures and/or NTM disease within various CF patient cohorts or at single centers varies dramatically,6,7 but in the
Disclosures: The authors are supported by the Cystic Fibrosis Foundation Research Development Grant (NICK15R0). a Department of Pediatrics, Children’s Hospital Colorado, University of Colorado Denver School of Medicine, 13123 East 16th Avenue, Box B-395, Aurora, CO 80045, USA; b Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA; c Department of Medicine, University of Colorado Anschutz Medical Campus, 13001 E. 17th Place, Aurora, CO 80045, USA * Corresponding author. Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206. E-mail address: [email protected] Clin Chest Med 37 (2016) 83–96 http://dx.doi.org/10.1016/j.ccm.2015.11.001 0272-5231/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
chestmed.theclinics.com
Nontuberculous mycobacterial (NTM) lung infections appear to be increasing in patients with cystic fibrosis (CF). Mycobacterium avium complex and Mycobacterium abscessus complex are the most frequently encountered NTM respiratory pathogens in patients with CF in most areas. Diagnosis of NTM lung disease in patients with CF generally follows American Thoracic Society and Cystic Fibrosis Foundation guidelines, with an emphasis on evaluating and treating all known comorbidities. Therapy for NTM in patients with CF depends on the species, resistance pattern, and extent of disease. Optimal management of patients with CF and NTM lung disease requires carefully considered treatment of both conditions.
84
Martiniano et al largest studies the overall prevalence is 6% to 13%.1,3,8–12 In a recent review of data from the US CF Patient Registry, the median state prevalence of NTM in patients with CF was 12%, although this ranged from 0% to 28% (Fig. 1). Significant spacial clustering of NTM was detected in Wisconsin, Arizona, Florida, and Maryland.13 The prevalence of NTM infection appears to be increasing within the CF population,1–3,9,14–17 as it is in the general population.18,19 For example, among patients with CF in Israel, NTM infection prevalence increased threefold from 5% in 2003% to 14.5% in 2011.16 The reasons for the increase in prevalence are uncertain but culture techniques, increased physician awareness, and more frequent diagnosis of “nonclassic” forms of CF in adulthood may contribute to the apparent increase in NTM prevalence observed in this population.14 Most NTM species recovered in CF samples in the United States are from either the Mycobacterium avium complex (MAC) or the Mycobacterium abscessus complex (MABSC).12 MAC has historically been the most common NTM isolated from respiratory specimens,20–23 and in the largest US survey it was present in up to 72% of patients with NTM-positive sputum cultures.9 Among patients with CF in the US Patient Registry during 2010 to 2011, 60% of positive cultures were for
MAC, although this ranged by state, from 29% in Louisiana to 100% in Nebraska and Delaware.12 The percentage of MABSC reported in patients with CF with NTM-positive sputum cultures has ranged between 16% and 68%,3,8,9,24 and it appears that the proportion of MABSC is increasing,1,2,25 with some centers reporting a greater frequency than MAC. In part, this variation may be due to geographic factors, as MABSC appears especially prevalent in Europe,3,8,24,25 and Mycobacterium simiae and MABSC are the most common species isolated in Israel.16,26 Differences in relative prevalence of MAC and MABSC may also relate to the age of the cohorts studied, as MAC is more often associated with older patients with CF, often diagnosed in adulthood, whereas MABSC is frequently seen in younger patients and those with more severe lung disease.3,27 Less frequently isolated species include Mycobacterium kansasii7,8,21,23 and Mycobacterium fortuitum.8,22,28,29
Individual Risk Factors for Nontuberculous Mycobacteria in Cystic Fibrosis Our understanding of individual risk factors for NTM in patients with CF is incomplete, as most reports have studied relatively small cohorts from
Fig. 1. State-level prevalence and significant (P
