You are in: eMedicine Specialties > Radiology > CHEST Lung, Nontuberculous Mycobacterial InfectionsArticle Last Updated: Apr 3, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 8
  Author: Anjali Agrawal, MBBS, Adjunct Assistant Professor of Radiology, Baylor College of Medicine; Consultant Radiologist, Teleradiology Solutions, India Anjali Agrawal is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America Coauthor(s): Anurag Agrawal, MBBS, Senior Scientist, Institute of Genomics and Integrative Biology, India Editors: Satinder P Singh, MD, Associate Professor of Radiology, Director of Cardiac CT, Director of Combined Cardiopulmonary and Abdominal Radiology, Department of Radiology, University of Alabama at Birmingham; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Eric J Stern, MD, Professor of Radiology, Adjunct Professor of Medicine, Adjunct Professor of Medical Education and Biomedical Informatics, University of Washington School of Medicine; Director of Thoracic Imaging, Harborview Medical Center; Associate Medical Staff, Seattle Cancer Care Alliance; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Clinical Assistant Professor of Radiology, University of Washington Medical School Author and Editor Disclosure Synonyms and related keywords: NTM, tuberculosis, TB, Mycobacterium avium-intracellulare complex, Mycobacterium kansasii, Mycobacterium xenopi, M avium-intracellulare complex, M kansasii, M xenopi, MAI complex, MAC, Mycobacterium tuberculosis, M tuberculosis, MTB INTRODUCTIONSection 2 of 8
  BackgroundNontuberculous mycobacteria (NTM) are environmental organisms that are normally found in soil and water. They have only recently been associated with disease. In 1968, Dr Wolinsky published the first comprehensive review, stating, "chronic pulmonary disease resembling tuberculosis [TB] represents the most important clinical problem associated with NTM."1 Since then, a variety of manifestations of NTM infection have been described, but the lungs remain the most commonly involved site. PathophysiologyThe 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.2 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 the US, whereas M kansasii is more common in the Midwest. The initial site of entry is probably the lung; granulomatous inflammation is the key pathologic feature. Disseminated disease associated with HIV may be secondary to the oral ingestion of contaminated water.3, 4 FrequencyUnited StatesNTM infection is not a reportable disease in the US, and the exact prevalence is not known.5 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. InternationalIn Canada and Europe, MAI complex is most common, followed by M xenopi. Mortality/MorbidityMortality is an uncommon outcome of NTM infection in nonimmunocompromised patients. RaceNTM infections appear to be more prevalent in whites, excluding patients with AIDS. The reason for this is not known. SexTwo 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 the absence of underlying pulmonary disease. AgeSee Sex, above. Clinical DetailsThe 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 CT Scan below), and (3) isolation of NTM from respiratory specimens on more than 1 occasion (see American Thoracic Society guidelines for details).3, 6, 7 Patients with underlying lung disease or immunosuppression are at highest risk for infection. However, immunocompetent subjects are also susceptible to the disease.8, 9, 10 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 a 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; adequate therapy usually results in a good clinical response.11 Preferred ExaminationThe 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 evidence of infiltrates (nodular or cavitary disease) are an essential adjunct for the microbiologic diagnosis.3, 6 Limitations of TechniquesNo single test, including microbiologic tests, yields results diagnostic of NTM infections. DIFFERENTIALSSection 3 of 8
Bronchiolitis Obliterans Organizing Pneumonia Lung, Postprimary Tuberculosis Lung, Primary Tuberculosis Pneumonia, Atypical Bacterial Pneumonia, Viral Sarcoidosis, Thoracic RADIOGRAPHSection 4 of 8
FindingsNTM infections are associated with a wide spectrum of radiologic findings.12, 13 In the most common group of patients—namely, elderly males with COPD—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 are commonly seen, with traction bronchiectasis evident in the most affected areas. Degree of ConfidenceIn 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 have 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/NegativesRegarding 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 findings on chest radiographs, 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. CT SCANSection 5 of 8
FindingsTypical diagnostic features of NTM infections (particularly those due to MAI complex) in immunocompetent patients without underlying lung disease are the following: (1) multiple small parenchymal nodules in a centrilobular pattern, (2) associated multifocal bronchiectasis involving more than 1 lobe, and (3) progressive fibrosis and atelectasis of the affected areas. HRCT is useful in identifying these patterns (see Images 3-4). In a large group of patients, the findings are similar to those of TB (see Radiograph). Reticulonodular changes, along with cavitation, may be seen in an upper-lobe distribution. The additional information provided by CT is limited to better anatomic delineation of cavitation and the extent of disease. Consolidation and cavitation are frequently seen. The cavities vary in size and are radiologically indistinguishable from postprimary TB (see Image 2). Endobronchial spread is the predominant mechanism of spread and can be seen in about half the cases. It is seen best on CT images as 5- to 10-mm centrilobular peribronchiolar opacities with clustering. It is unusual to see extensive adenopathy in this patient group. Pleural effusions are infrequent but not rare (10-20%). The second group of patients consists of middle-aged or elderly women without a history of lung disease. The symptoms are typically milder than those in other patients; the radiographs show scattered reticulonodular opacities without an upper-lobe predominance. CT imaging reveals more extensive disease with scattered centrilobular nodules, a tree-in-bud pattern, and focal bronchiectasis (see Images 3-4). In some cases, atelectasis and severe bronchiectasis of the middle lobe and/or lingula may be the only manifestation (see Image 5). Usually, no cavitation, pleural effusion, or extensive adenopathy is depicted. Although MAI infections can be associated with a wide variety of radiologic patterns, findings of multifocal bronchiectasis with centrilobular nodules and patchy consolidation are highly predictive. When seen in its typical locations of lingula or middle lobe in middle-aged females, MAI complex is also referred to as Lady Windermere syndrome. The presentation of immunocompromised patients is entirely different from the patterns mentioned above. Patients with clinical infection may have no radiographic abnormalities, presumably because of inadequate inflammatory response. Alternatively, lymphadenopathy and pleural effusions may be the only abnormalities, with no evidence of parenchymal disease (see Image 6). In other patients, segmental or lobar consolidation may be seen. Miliary spread is seen occasionally. The most common pattern is scattered alveolar opacities and bilateral nodules, but this is not specific for the disease (see Images 7-8). A high index of suspicion and microbiologic investigation are required for diagnosis. Unusual radiographic presentations of NTM infections include solitary pulmonary nodules or masses (see Image 9). The diagnosis is usually incidental in otherwise asymptomatic patients being examined for a malignancy. In patients with HIV infection, a high index of suspicion must be maintained because a wide spectrum of radiologic findings can be seen. The disease can resemble disseminated primary TB or can cause localized pneumonia. Lymphadenopathy and/or pleural effusions are common. In patients with these findings, CT aids in the identification of subtle disease that is missed on the chest radiographs. Lymph nodes with hypoattenuating centers that suggest necrosis are associated with mycobacterioses (see Image 6). CT is more sensitive than other techniques in the detection of cavitation (see Image 2) and effusions. Subtle centrilobular nodules (see Image 7) may be the only sign of infection in immunocompromised patients. In summary, NTM infection of the lung is a diagnosis that requires the radiologic or pathologic demonstration of disease, followed by definitive microbiologic isolation of the organism. Degree of ConfidenceCT findings of NTM infections are often nonspecific. However, typical patterns such as multifocal bronchiectasis with patchy consolidation and centrilobular nodules have been defined; these have a high positive predictive value. In bronchiectatic patients with multiple small lung nodules whose culture results are positive for MAI complex, CT has a sensitivity of 80%, a specificity of 87%, and an accuracy of 86%. False Positives/NegativesAlthough certain patterns on HRCT scans are associated with high specificity, false-positive results can be seen with any radiographic presentation. Atypical presentations of pulmonary TB can mimic those of NTM lung disease, as can those of granulomatous fungal infections. The high sensitivity of HRCT results in a low false-negative rate in immunocompetent patients. Immunocompromised patients usually have abnormalities on CT scans; however, these findings can be atypical, and parenchymal disease can be subtle. INTERVENTIONSection 6 of 8
Most NTM infections are resistant to pyrazinamide and/or isoniazid (INH). The duration of therapy is also longer with NTM (typically, 12 mo after negative culture findings are obtained) than with tuberculosis. Newer macrolides and fluoroquinolones are more effective in these infections, and the precise drug regimen is different for different members of this group. Because human-to-human infection is rare, directly observed treatment by public health agencies is not required.14 MULTIMEDIASection 7 of 8
REFERENCESSection 8 of 8
Lung, Nontuberculous Mycobacterial Infections excerpt Article Last Updated: Apr 3, 2008 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
