Multicenter Study of Prevalence of Nontuberculous Mycobacteria in Patients with Cystic Fibrosis in France

Abstract

We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The "new" species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%).Nontuberculous mycobacteria (NTM) have emerged as "new" pathogens in cystic fibrosis (CF) patients over the last 2 decades (10). CF centers worldwide have reported isolation of NTM from the respiratory tracts of CF patients, with prevalence values ranging from 5% to 20% (5,6,8,9,13,14,16,19,22,25). Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) species are the most frequently isolated NTM and together account for Ͼ95% of NTM lung diseases affecting CF patients. The MAC, a member of the subgroup comprising slowly growing mycobacteria, ranks first in North America (22), whereas the MABSC, a member of the subgroup comprising rapidly growing mycobacteria, seems to predominate in Western Europe (15,23,25) and is also more prevalent than the MAC in Israel (19).Previous studies have reported isolation of NTM from 6.6 to 9.8% of French CF cohorts (9,23,25). These studies also reported a much higher isolation rate for MABSC than for MAC or other NTM species (23,25). However, these studies were done exclusively in pediatric CF centers in Paris. This may have distorted the results since MABSC species are more prevalent than MAC species in children (23). Moreover, the epidemiology of NTM in Paris does not necessarily reflect the situation in other regions of France. For example, studies involving non-CF patients have reported higher rates of NTM disease in urban areas (20). Moreover, previous French studies were performed before M. abscessus (now M. abscessus sensu lato, or the MABSC) was shown to include at least three distinct species, M. abscessus (sensu stricto) (hereafter referred to as M. abscessus), Mycobacterium massiliense, and Mycobacterium bolletii (1,3). The prevalences of these three species in CF patients in France were therefore unknown.We thus conducted a large, prospective, nationwide study addressing NTM prevalence in CF patients in France. This study shows relatively low prevalence figures for French CF centers. It also provides evidence that MABSC species are currently the most prevalent NTM in the French CF populat...

Mycobacterium abscessus cording prevents phagocytosis and promotes abscess formation

“…Although M. abscessus infections are more common in patients with underlying pulmonary pathology, ∼30% of cases occur in apparently healthy subjects (52). In recent years the frequency and severity of pulmonary infections caused by the M. abscessus complex in CF patients has been well established (3,5,53), but very little is known about the mechanisms that give the M. abscessus R variant an advantage in resisting the hostile CF lung environment, where inflammation and oxygen radicals are capable of inhibiting colonization by most other bacteria. Accumulation of the particular bronchial mucus associated with the CF transmembrane conductance regulator (CFTR) defect allows bacteria such as Pseudomonas aeruginosa or M. abscessus to colonize CF lungs.…”

“…The kanamycin cassette of pMV306 (58) was replaced with the zeocin cassette, which was amplified from pCR-BluntII-TOPO (Invitrogen) using the primers Zeo-up (5′-AAA GCT AGC TTA CAA TTT CCT GAT G-3′; NheI underlined) and Zeo-lo (5′-AAC TAG TCA GTC CTG CTC CTC G-3′; SpeI underlined) and ligated into the NheI/SpeI-restricted pMV306 product to generated (1), M. abscessus are rapidly engulfed by macrophages attracted by chemotaxis to the injection site (2 and 3). Infected macrophages migrate from the vasculature to the nervous tissues, become heavily infected (4), and eventually die (5). Apoptosis leads to the release of S variants (blue pathway) that subsequently are phagocytosed by newly recruited macrophages to form cellular aggregates (6).…”

“…M. abscessus lung disease is highly prevalent in patients with cystic fibrosis (CF) and is becoming a major issue for most CF centers worldwide (3)(4)(5)(6). Although M. abscessus is an RGM, it can persist and cause lung disease with caseous lesions (7).…”

Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update

“…Although MAC is more prevalent in North America, M. abscessus is more common in Europe and Israel. [102][103][104] In France, MAC was detected in older patients with less severe disease. 104 Thus, it appears that MAC and M. abscessus may target different subpopulations of people with CF.…”

Inhaled therapies, azithromycin andMycobacterium abscessusin cystic fibrosis patients

“…N ontuberculous mycobacteria (NTM) are increasingly recognised as common respiratory pathogens in cystic fibrosis (CF) patients, with an overall NTM prevalence ranging between 6.6% and 13% in large prospective studies [1,2]. The NTM most frequently isolated from CF patients are Mycobacterium abscessus complex (MABSC) (also called Mycobacterium abscessus sensu lato, comprising the closely related species Mycobacterium asbcessus sensu stricto, Mycobacterium massiliense and Mycobacterium bolletii) and Mycobacterium avium complex.…”