The challenge of nontuberculous mycobacteria in patients with cystic fibrosis.

The case report by Hayes in the June 2005 issue of the Journal 1 illustrates a difficult area in the care of patients with cystic fibrosis (CF). It highlights several important points for the CF practitioner that relate to CF as a risk factor for pulmonary nontuberculous mycobacteria (NTM) infection and the very difficult diagnostic and management problems NTM pose in these patients. A recent multicenter study demonstrated that CF is a significant risk factor for the presence of NTM, finding a prevalence of 13% with Mycobacterium avium and Mycobacterium abscessus accounting for the majority of isolates. While structural lung disease is a general risk factor for NTM, this study showed that patients with milder lung disease, as assessed by FEV1, were the most likely to have NTM in their sputa. Other variables associated with NTM-positive sputa in this study were older age, low body-mass index, and the presence of Staphylococcus aureus in the sputum. The mechanisms by which CF patients acquire and retain NTM are still undefined. Potential explanations include changes in the ionic milieu of the lower airways favoring the growth of NTM, alterations to the mucociliary escalator resulting in the retention of organisms over time, and as yet undetermined genetic or immunologic factors. The effect of NTM on the clinical course of CF is poorly understood. As in the accompanying case report, NTM has been anecdotally associated with catastrophic declines in lung function. In contrast however, a case of tissue-invasive M abscessus that did not progress to clinical disease for over a decade has also been reported. A recent cohort study attempted to evaluate the impact of NTM in patients with CF. Between control and NTM-positive subjects, over a fifteen month period, there were no differences in chest radiographic findings, and no statistically significant differences in lung function decline, although a trend was noted in subjects meeting the American Thoracic Society (ATS) microbiologic criteria for NTM disease. In light of these results, and considering that the symptoms of NTM disease can closely mimic those of a CF exacerbation, the ATS diagnostic criteria based on symptoms, chest x-rays, and microbiologic findings are inadequate for the CF population. Alternative approaches for evaluating NTM in the sputa of CF patients exist but still require validation. The treatment of pulmonary NTM in CF patients follows the published guidelines for treatment in non-CF patients. Drug levels should be considered after starting treatment due to alterations in drug absorption and metabolism that can occur in CF. Pretreatment exposure to multiple antimicrobials, the susceptibilities of other respiratory pathogens to some antimycobacterial agents, and the high potential for drugdrug interactions and medication side effects in patients already exposed to polypharmacy can further complicate management. Some NTM infections, particularly those with M abscessus, may not respond well to medical therapy despite compliance with an appropriate regimen and adequate drug levels. In these cases, surgical resection may be appropriate but should be considered with caution in patients with CF and only at experienced centers. Lung transplantation has been successfully performed on NTM-positive CF patients, but this remains controversial due to the potential risk of posttransplant immune suppression leading to disseminated disease and even death. The emergence of NTM as respiratory pathogens in CF presents many challenges in both diagnosis and management. With the improving survival in CF, these challenges will become increasingly common, and it will be important to better define which patients will most benefit from NTM therapy.