Background: Nontuberculous mycobacteria (NTM) are environmental organisms that are normally found in soil and water. They have only recently been associated with disease. In 1979, Dr Wolinsky published the first comprehensive review stating, "chronic pulmonary disease resembling tuberculosis [TB] represents the most important clinical problem associated with NTM." Since then, a variety of manifestations of NTM infection have been described, but the lungs remain the most commonly involved site.

Pathophysiology: The best-studied NTM are Mycobacterium avium-intracellulare complex (MAI complex) and Mycobacterium kansasii. Nontuberculosis mycobacteria are pathogenic mycobacteria, other than Mycobacterium leprae, that are not part of the tuberculosis complex. There are many other potentially pathogenic NTM organisms.

Chronic pulmonary disease remains the most common localized manifestation of infection. MAI complex is the most common pathogen in the US, followed by M kansasii, whereas MAI complex and then Mycobacterium xenopi are most common in Canada and in parts of Europe.

Aerosolized water is currently believed to be the most likely source of infection. Human-to-human or animal-to-human transmission is rare. Human disease is correlated with the geographic concentration of NTM. That is, MAI complex is commonly seen in southeast parts of US, whereas M kansasii is more common in the Midwest. The initial site of entry is probably the lung, and granulomatous inflammation is the key pathologic feature. Disseminated disease associated with HIV may be secondary to the oral ingestion of contaminated water.

Frequency:

• In the US: NTM infection is not a reportable disease in the US, and the exact prevalence is not known. Currently, more isolates are of MAI complex than of Mycobacterium tuberculosis (MTB). MAI complex is the most common pathogen in the US, followed by M kansasii, but the frequency is certainly dependent on the particular patient population.

• Internationally: In Canada and Europe, MAI complex is most common, followed by M xenopi.

Mortality/Morbidity: Mortality is an uncommon outcome of NTM infection in non-immunocompromised patients.

Race: NTM infections appear to be more prevalent in whites, excluding patients with AIDS. The reason for this observation is not known.

Sex: Two typical patterns of NTM infections of the lung have been noted. Elderly males with chronic obstructive pulmonary disease (COPD) are more commonly affected with the more prevalent pattern that mimics TB, whereas middle-aged to elderly women characteristically have focal bronchiectasis and scarring in absence of underlying pulmonary disease.

Age: See Sex above.

Clinical Details: The diagnosis of NTM infection can be made in the presence of the following: (1) clinical signs and symptoms compatible with mycobacteriosis, (2) compatible chest radiographic or high-resolution computed tomographic (HRCT) findings (see Cat Scan below), and (3) isolation of NTM from respiratory specimens on more than 1 occasion (see American Thoracic Society guidelines for details).

Patients with underlying lung disease or immunosuppression are at highest risk for infection. However, immunocompetent subjects are also susceptible to the disease. Clinically, the major symptoms are similar to those associated with TB, namely, cough, hemoptysis, fever, night sweats, and/or weight loss. The clinical presentation is generally independent of the species, but M kansasii is thought to behave more like TB than the others. Most infections are related to MAI complex, except in certain areas where M kansasii is predominant.

The reliable diagnosis or exclusion of the disease is difficult in many cases despite use of the guidelines mentioned above.

In immunocompromised patients who have clinically high likelihood of NTM disease, infection may be presumed with any isolation of NTM in respiratory specimens. In contrast, more stringent proof, such as pathologic specimens demonstrating granulomas and/or acid-fast bacilli, may be appropriate in unusual clinical settings.

As always, other diseases should be excluded before the diagnosis is made, and the absence of a response to therapy should prompt reassessment. The isolation of NTM from tissues where contamination is unlikely is usually considered proof of disease. Treatment should be tailored to the particular strain isolated, and adequate therapy usually results in a good clinical response.

Preferred Examination: The increasing efficiency of microbiologic laboratories in isolating small quantities of organisms has made the distinction between colonization and infection more difficult. Therefore, diagnostic guidelines from the American Thoracic Society suggest that the presence of symptoms and radiographic infiltrates (nodular or cavitary disease) are an essential adjunct for the microbiologic diagnosis.

Limitations of Techniques: No single test, including microbiologic tests, offers results diagnostic of NTM infections.

DIFFERENTIALS

Bronchiolitis Obliterans Organizing Pneumonia
Lung, Postprimary Tuberculosis
Lung, Primary Tuberculosis
Pneumonia, Atypical Bacterial
Pneumonia, Viral
Sarcoidosis, Thoracic

X-RAY

Findings: NTM infections are associated with a wide spectrum of radiologic findings.

In the most common group of patients, namely, elderly males with chronic obstructive airway disease, the typical findings include linear and nodular opacities involving the apical and posterior segments of the upper lobes and the superior segments of the lower lobes (see Image 1). Involvement of multiple segments is common. Unlike those of TB, NTM lesions are indolent and progress slowly. Marked fibrosis and atelectasis of affected zones is commonly seen, with traction bronchiectasis in the most affected areas.

Degree of Confidence: In NTM infections, chest radiographic findings are usually not specific, and they can also be seen in TB, granulomatous fungal infections, sarcoidosis, and bronchiolitis obliterans and organizing pneumonia (BOOP). In appropriate clinical contexts (as described above), typical findings are associated with a high predictive value. For example, patients with MAI infection may be distinguished from those with MTB by the presence of widespread bronchiectasis, particularly if it involves the right middle lobe and the lingula. Cavitation is usually associated with positive sputum results.

False Positives/Negatives: Regarding false-positive results, normal anatomic variants are usually not confused with NTM infection. On the other hand, granulomatous processes such as TB, fungal infections, and sarcoidosis can all resemble NTM infections. Often, the colonization of a scarred or bronchiectatic lung cannot be distinguished from active infection causing scarring and/or bronchiectasis.

Regarding false-negative results, immunosuppressed patients commonly have normal chest radiographic findings, or detectable parenchymal disease is absent. Findings of focal bronchiectasis associated with early NTM infections are also easily missed. Only 70% of patients with established bronchiectasis, as depicted on CT scans, have a detectable abnormality on chest radiographs.