Nontuberculous Mycobacterial Pulmonary Disease

Stacey Martiniano, MD, and Paul C. Stillwell, MD, FAAP

Introduction/Etiology/Epidemiology

•There are more than 150 identified species of nontuberculous mycobacteria (NTM) that are ubiquitous in the environment; very few exposures result in infection or disease in the general pediatric population.

•In a healthy child, the most common disease due to NTM is lymphade-nitis, most typically caused by Mycobacterium avium complex (MAC) in the cervical lymph nodes. Pulmonary NTM infection is rare.

•The prevalence of NTM pulmonary infection is highest in the population with cystic fibrosis (CF) and is increasing. In 2015, ≤20% of patients with CF in North America had an isolated NTM species in their sputum.

•Children with HIV infection and children treated with immunomodulating biological agents may also be at risk for pulmonary and disseminated NTM infection.

•The most common NTM organisms isolated in patients in the United States are those of the MAC and Mycobacterium abscessus complex, with less frequent isolation of Mycobacterium kansasii and Mycobacterium fortuitum.

•There is considerable geographic variation in the prevalence and species of NTM across the United States, which may be related to environmental water vapor pressure.

•There may be a risk of person-to-person spread of NTM in patients with CF.

Clinical Features

•Most NTM organisms may produce chronic, indolent symptoms at presentation.

•Pulmonary symptoms include chronic cough, increased sputum production, dyspnea, and hemoptysis.

•Possible constitutional symptoms include fatigue, low-grade fever, and night sweats.

•There may be an associated decrease in pulmonary function.

Diagnostic Considerations

•Two or more positive sputum culture findings or 1 bronchoalveolar lavage or lung biopsy culture for NTM are required to establish the diagnosis of NTM pulmonary disease.

—NTM isolation requires culture on both liquid and solid media, with incubation for at least 6 weeks, to ensure adequate time for isolation of “slow-growing” species, such as MAC.

•In addition to meeting the above microbiological criteria, ≥1 of the following clinical or radiographic features must be present:

—Pulmonary symptoms, including

▪Unexplained decline in pulmonary function test results

▪Increased cough, sputum, dyspnea, or hemoptysis

—Progressive radiologic findings, such as cavitary disease, nodules, tree-in-bud opacities, and parenchymal consolidation

•There must also be appropriate exclusion of other diagnoses.

—In a patient with CF, this would include adequate treatment of underlying CF pulmonary disease and treatment of CF copathogens and comorbidities.

—If clinical symptoms and findings persist, then the diagnosis of NTM pulmonary disease can be established.

•Skin tests are not available for NTM; polymerase chain reaction testing of sputum is under development.

•Notably, infection with MAC and Mycobacterium marinum may cause a false-positive tuberculin skin test finding.

•Typically, pediatric and adult patients with CF are screened for NTM infections with sputum acid-fast bacilli stains and cultures annually if they can expectorate and more frequently if NTM infection is clinically suspected.

•Chest radiographs and computed tomographic images in patients with CF and M abscessus complex are shown in Figures 59-1 and 59-2.

Treatment

•Treatment of NTM infections is challenging because of their slow growth and intrinsic resistance to antibiotics.

•Therapeutic regimens typically consist of 3–4 drugs for treatment periods of about 1 year.

•Treatment of MAC typically consists of a prolonged course of 3 oral agents with amikacin (inhaled or intravenous [IV]) added for cavitary or severe disease.

•Treatment of M abscessus complex often includes prolonged IV antibiotics for several weeks to months during an intensive phase, followed by a chronic suppressive phase of inhaled and oral medications.

•The antibiotics can be difficult to tolerate because of side effects, and the patient must be monitored diligently, which may include regular assessment of symptoms, laboratory liver and renal function testing, electrocardiograms, audiograms, and visual acuity and color vision testing, depending on the drug regimen.

•The goal of treatment is to obtain 12 months of negative NTM culture findings.

Prognosis

•There is evidence that NTM pulmonary disease can accelerate disease progression in some patients with CF.

•Treatment can improve clinical and constitutional symptoms and either stabilize or reverse some lost pulmonary function.

•Clearance of the NTM from the sputum is possible but can be difficult, especially in M abscessus complex infection.

•Even with clearance of sputum, recurrence of the same NTM infection or infection with a second NTM species is common in CF.

When to Refer

•Refer the patient if NTM is suspected or isolated from the sputum, with or without the presence of CF.

•Refer the patient if the diagnosis is in doubt.

•Bronchoscopy with bronchoalveolar lavage is needed for specimen collection.

•Refer the patient if the response to therapy is suboptimal.

•Refer the patient if the side effects of therapy are limiting treatment.