Clinical significance of a first positive nontuberculous mycobacteria culture in cystic fibrosis

Abstract

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 FEV1 (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 FEV1 at the time of first positive NTM culture (72% vs. 84 or 86%; P = 0.02) and FEV1 decline in the prior year (-5.8%/yr vs. -0.7%/yr [P = 0.009] or -0.4%/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.

Figure 1.

Change in percent predicted FEV₁ over time from 1 year before to 3 years after the date of the first positive culture in the three nontuberculous mycobacteria (NTM) groups. Subjects are divided into those with transient infection, those with persistent infection, and those with active disease. The vertical dashed line (at time 0) represents the time of first positive NTM culture. Subjects with active NTM disease have a lower baseline FEV₁ at time of first positive culture, an increased rate of decline in FEV₁ over the 1 year preceding the first positive culture, and an accelerated rate of decline in FEV₁ after the first positive culture when compared with the other groups. There were no differences in baseline FEV₁ or decline in FEV₁ for subjects with transient or persistent infection before or after the first positive NTM culture.

Figure 2.

Probability of detecting a second nontuberculous mycobacteria (NTM) species after culturing a first NTM by Kaplan-Meier analysis, separated by initial positive NTM culture species. Twenty-four percent of subjects with Mycobacterium avium complex (MAC) initially grew a second NTM species during 5 years of follow-up, whereas 34% of subjects with M. abscessus first grew a second NTM species at 5 years. Overall, 26% of subjects grew a second NTM species at 5 years, and 36% grew a second NTM species at 10 years.

Figure 3.

Change in FEV₁ percent predicted (mean, SD) in subjects treated for active nontuberculous mycobacteria (NTM) disease from the year before the date of the first positive culture, time of first NTM culture, time of treatment initiation, and 1 year after treatment initiation. The mean FEV₁ at the time of treatment initiation was significantly lower than the mean FEV₁ 1 year before the first positive NTM culture.