Pulmonary Nontuberculous Mycobacterial Infection Research Articles

Nontuberculous Mycobacterial Sensitization in the United States

The prevalence of pulmonary nontuberculous mycobacterial (NTM) infections in the United States appears to be rising, but it is unclear if this is due to enhanced detection or actual increases in the burden of infection. Temporal changes in the epidemiology of Mycobacterium intracellulare sensitization may help explain recently observed trends in pulmonary NTM infections. Describe the epidemiology of M. intracellulare sensitization in the United States in 1971-1972 and 1999-2000. We studied nationally representative cohorts of the United States' noninstitutionalized civilian population participating in the 1971-1972 and 1999-2000 National Health and Nutrition Examination Surveys (NHANES). Participants were skin tested with M. intracellulare antigen and sensitization prevalence was compared across NHANES surveys and between participant subgroups. Logistic regression was used to identify associations between participant characteristics, environmental factors, and NTM sensitization. The 1971-1972 and 1999-2000 NHANES cohorts included 1,490 and 7,384 individuals, respectively. Between 1971-1972 and 1999-2000, the prevalence of M. intracellulare sensitization increased from 11.2% (95% confidence interval, 9.2-13.5%) to 16.6% (95% confidence interval, 13.2-20.6%). On multivariate analysis of the 1999-2000 cohort, age, sex, race, birthplace, education, and occupation were strongly associated with M. intracellulare sensitization. In 1999-2000, an estimated one in six persons in the United States demonstrated M. intracellulare sensitization, up from one in nine persons in 1971-1972. The observed rising prevalence of sensitization is consistent with observed increases in the rates of pulmonary NTM infections in the United States.

Aerosolized amikacin for treatment of pulmonary Mycobacterium aviuminfections: an observational case series

BackgroundCurrent systemic therapy for nontuberculous mycobacterial pulmonary infection is limited by poor clinical response rates, drug toxicities and side effects. The addition of aerosolized amikacin to standard oral therapy for nontuberculous mycobacterial pulmonary infection may improve treatment efficacy without producing systemic toxicity. This study was undertaken to assess the safety, tolerability and preliminary clinical benefits of the addition of aerosolized amikacin to a standard macrolide-based oral treatment regimen.Case PresentationsSix HIV-negative patients with Mycobacterium avium intracellulare pulmonary infections who had failed standard therapy were administered aerosolized amikacin at 15 mg/kg daily in addition to standard multi-drug macrolide-based oral therapy. Patients were monitored clinically and serial sputum cultures were obtained to assess response to therapy. Symptomatic improvement with radiographic stabilization and eradication of mycobacterium from sputum were considered markers of success.Of the six patients treated with daily aerosolized amikacin, five responded to therapy. All of the responders achieved symptomatic improvement and four were sputum culture negative after 6 months of therapy. Two patients became re-infected with Mycobacterium avium intracellulare after 7 and 21 months of treatment. One of the responders who was initially diagnosed with Mycobacterium avium intracellulare became sputum culture positive for Mycobacterium chelonae resistant to amikacin after being on intermittent therapy for 4 years. One patient had progressive respiratory failure and died despite additional therapy. There was no evidence of nephrotoxicity or ototoxicity associated with therapy.ConclusionAerosolized delivery of amikacin is a promising adjunct to standard therapy for pulmonary nontuberculous mycobacterial infections. Larger prospective trials are needed to define its optimal role in therapy of this disease.

Evaluation and management of patients with pulmonary nontuberculous mycobacterial infections

Nontuberculous mycobacteria (NTM) are emerging pathogens increasingly associated with chronic pulmonary disease. NTM are environmental saprophytes found in soil, dust and water and, unlike Mycobacterium tuberculosis, NTM are not transmitted from person to person. Pulmonary disease caused by NTM is a particular problem in older people without underlying immune compromise. The diagnosis of NTM pulmonary disease usually requires either multiple respiratory cultures that grow NTM or heavy growth of NTM from a single bronchoscopy or lung-biopsy specimen. High resolution computed tomography is the most useful radiographic study for diagnosis and to determine the extent of disease. Treatment includes multiple medications with activity against the particular NTM species, as single-drug therapy is likely to select for resistant organisms. Data demonstrating the effectiveness of specific drug regimens for NTM pulmonary disease are limited. Clarithromycin and azithromycin form the backbone of most treatment regimens because these drugs are active against many NTM species. Drug tolerability and cost are the major barriers to successful treatment of NTM pulmonary disease. Adjunctive therapies, including mucus clearance techniques and appetite stimulants, are unproven but may be of value in management of NTM pulmonary disease. Multicenter, randomized trials of macrolide-based therapies are sorely needed to determine the safest and most effective treatments for NTM pulmonary disease.

Prospective Analysis of Cystic Fibrosis Transmembrane Regulator Mutations in Adults With Bronchiectasis or Pulmonary Nontuberculous Mycobacterial Infection

Bronchiectasis and pulmonary infection with nontuberculous mycobacteria (NTM) may be associated with disease-causing mutations in the cystic fibrosis transmembrane regulator (CFTR). Fifty adult patients at Stanford University Medical Center with a diagnosis of bronchiectasis and/or pulmonary NTM infection were prospectively characterized by sweat chloride measurement, comprehensive mutational analysis of CFTR, and sputum culture results. A de novo diagnosis of cystic fibrosis (CF) was established in 10 patients (20%). Patients with CF were more likely than those without CF to have mucus plugging seen on chest high-resolution CT, and women with a CF diagnosis were thinner, with a significantly lower mean body mass index than the non-CF subjects. Thirty CFTR mutations were identified in 24 patients (50% prevalence). Sweat chloride concentration was elevated > 60 mEq/dL (diagnostic of CF) in seven patients (14%), and from 40 to 60 mEq/dL in eight patients (16%). The frequency of CFTR mutations was elevated above that expected in the general population: heterozygous DeltaF508 (12% vs 3%), R75Q (14% vs 1%), and intron 8 5T (17% vs 5 to 10%). Other known CFTR mutations identified were V456A, G542X, R668C, I1027T, D1152, R1162L, W1282X, and L183I. Three novel CFTR mutations were identified: A394V, F650L, and C1344S. Mutations in CFTR that alter RNA splicing and/or functional chloride conductance are common in this population, and are likely to contribute to the susceptibility and pathogenesis of adult bronchiectasis and pulmonary NTM infection. Careful clinical evaluation for disease cause should be undertaken in this clinical context.

Septic Arthritis Caused by Mycobacterium kansasii in a Prosthetic Knee Joint

Mycobacterium kansasii is a relatively common cause of nontuberculous mycobacterial pulmonary infection. Septic arthritis caused by Mycobacterium kansasii, on the other hand, is rare. Reported here for the first time is the case of an 82-year-old patient with an infection of a prosthetic knee joint with Mycobacterium kansasii.

Mycobacterium abscessus Pulmonary Infection Presenting as a Solitary Pulmonary Nodule

Nontuberculous mycobacterial pulmonary infection is a rare cause of a solitary pulmonary nodule. All previously reported cases were caused by Mycobacterium avium complex, and a solitary pulmonary nodule caused by other NTM species has been very rarely reported. We describe the first case of Mycobacterium abscessus infection presenting as a solitary pulmonary nodule in a 51-year-old asymptomatic adult patient.

Bilateral Bronchiectasis and Bronchiolitis at Thin-Section CT: Diagnostic Implications in Nontuberculous Mycobacterial Pulmonary Infection

Bilateral Bronchiectasis and Bronchiolitis at Thin-Section CT: Diagnostic Implications in Nontuberculous Mycobacterial Pulmonary Infection

Anti-IFN-γ Autoantibodies in Disseminated Nontuberculous Mycobacterial Infections

Although many patients with disseminated nontuberculous mycobacterial disease have molecular defects in the IFN-gamma/IL-12 axis, recent case reports have shown autoantibodies against IFN-gamma associated with severe nontuberculous mycobacterial infections. To check this finding in an independent population, we screened 35 patients with either disseminated or pulmonary nontuberculous mycobacterial infections for whom no molecular defect was known. We identified high-titer-neutralizing anti-IFN-gamma IgG in the plasma of six patients. All six patients were female, parous, of East Asian descent, and had disseminated infection, predominantly with rapidly growing mycobacteria. The anti-IFN-gamma IgG had in vitro biological activity on the IFN-gamma-dependent phosphorylation of STAT-1 as well as on the IFN-gamma-dependent up-regulation of TNF-alpha and IL-12. In contrast, this anti-IFN-gamma Ab had no effect on IFN-alpha-dependent STAT-1 phosphorylation. These patients confirm a novel syndrome linking autoimmunity and immunodeficiency.

Hypothesis on the Evolution of Cavitary Lesions in Nontuberculous Mycobacterial Pulmonary Infection: Thin-Section CT and Histopathologic Correlation

The objectives of our study were to evaluate the thin-section CT findings of the cavitary form of nontuberculous mycobacterial pulmonary infection and correlate these imaging findings with the histopathologic findings concerning the development of bronchiectasis and of centrilobular nodules and cavitary lesions. We retrospectively reviewed thin-section CT scans (2.5-mm collimation, both axial and coronal reformation images) of 24 cases (male-female ratio, 13:11; mean age, 61 years; age range, 43-82 years) of the cavitary form of culture-proven Mycobacterium avium-intracellulare complex pulmonary infection including two cases with lobectomy specimens. Any changes in CT findings detected on the follow-up CT scans that were available for seven patients (follow-up interval, 6-24 months; mean, 12 months) were also assessed. Thin-section CT findings were bronchiectasis (24/24 patients, 100%), a patent bronchus running into a cavitary lesion (the "feeding bronchus" appearance) (18/24, 75%), nodules less than 10 mm (17/24, 71%), centrilobular nodules (17/24, 71%), nodules of 10-30 mm (13/24, 54%), peribronchial nodules (8/24, 33%), lobular consolidation (6/24, 25%), bronchial wall thickening (4/24, 17%), and consolidation (2/24, 8%). Two lobectomy specimens showed large cavitary consolidations with the feeding bronchus appearance on pathologic specimens. In two patients, small peribronchial nodules had changed into cavitary nodules with the feeding bronchus appearance on follow-up CT, which represented inflamed focal cystic bronchiectasis. In the cavitary form of M. avium-intracellulare complex pulmonary infection, the feeding bronchus appearance is another very frequent thin-section CT finding. This appearance may suggest that peribronchial nodules of M. avium-intracellulare complex infection evolve into inflamed focal cystic bronchiectasis manifesting as cavitary lesions.

Bilateral Bronchiectasis and Bronchiolitis at Thin-Section CT: Diagnostic Implications in Nontuberculous Mycobacterial Pulmonary Infection

To determine frequency of nontuberculous mycobacterial (NTM) pulmonary infection in patients with bilateral bronchiectasis and bronchiolitis at chest computed tomography (CT) and whether CT findings are indicative of Mycobacterium avium-intracellulare complex (MAC) infection. Institutional review board approved this research study; patient informed consent (not required) was obtained from all patients to perform CT. From July 2000 to December 2002, 126 consecutive patients, who were suspected of having NTM pulmonary infection at helical CT (120 kVp, 70 mA, 2.5-mm collimation, pitch of 6) with findings of bilateral bronchiectasis and bronchiolitis, were included. Of these, 105 patients underwent study for diagnosis of NTM disease. Medical records and CT scans were reviewed for final diagnoses. Clinical and chest CT findings in patients with NTM disease and those with other airway diseases were compared (unpaired t test, chi(2) test, or Fisher exact test). NTM pulmonary infection was seen in 36 (34%) of 105 patients; NTM was definite in 32 (30%) and probable in four (4%). In decreasing order of frequency, organisms involved were MAC in 18 patients (50%), with M avium in 10 and M intracellulare in eight, Mycobacterium abscessus in 14 (39%), Mycobacterium kansasii in one (3%), and Mycobacterium fortuitum in one (3%); organisms were unidentifiable in two (6%). Female (P = .031) nonsmokers (P = .037) with history of treatment for Mycobacterium tuberculosis (P = .002), sputum smear positive for acid-fast bacilli (P < .001), and thin-section CT findings of bronchiolitis in more than five lobes with bronchiectasis (P = .011), lobular consolidation (P = .010), and a cavity (P < .001) were related to diagnosis of NTM pulmonary infection. About one-third of patients with thin-section CT findings of bilateral bronchiectasis and bronchiolitis have NTM pulmonary infection; in these situations, MAC and M abscessus are two most frequent causative organisms. Thin-section CT findings of bronchiectasis and bronchiolitis involving more than five lobes, especially when associated with lobular consolidation or a cavity, are highly suggestive of NTM pulmonary infection.

Radiographic and CT findings of nontuberculous mycobacterial pulmonary infection caused by Mycobacterium abscessus.

The purpose of our study was to describe the radiographic and CT findings in patients with pulmonary infections caused by Mycobacterium abscessus, one of the more common rapidly growing nontuberculous mycobacteria that cause lung disease. The main radiologic and CT manifestations of M. abscessus lung infection are bilateral small nodular opacities, bronchiectasis, and cavity formation.

Endobronchial carcinoid tumor combined with pulmonary non-tuberculous mycobacterial infection: report of two cases

We report here two cases of endobronchial carcinoid tumor complicated with pulmonary infection with non-tuberculous mycobacteria (NTM). Case 1 was an 81-year-old woman with the left lower lobe atelectasis. Bronchoscopy showed complete obstruction of the left basal bronchus by a tumor and a sleeve lower lobectomy with mediastinal lymph node dissection was performed. Pathological examination showed typical carcinoid located in the left basal bronchus and many caseous granulomas containing mycobacteria in the lung parenchyma distal to the bronchus. Bacterial examinations of sputum and gastric juice after the operation showed a growth of Mycobacterium kansasii. Case 2 was a 50-year-old woman with the atelectasis of the left upper division. Bronchoscopy showed complete obstruction of the left upper division bronchus by a tumor and a left upper lobectomy with mediastinal lymph node dissection was performed. Pathological examination showed typical carcinoid located in the left upper division bronchus and many caseous granulomas in the lung parenchyma distal to the bronchus. The Ziehl-Neelsen stain showed many mycobacteria in these granulomas and they were identified as Mycobacterium avium by PCR analysis. Although NTM are not well recognized as possible pathogens of pulmonary infection related to bronchial obstruction by endobronchial carcinoma, our experiences rouse a caution to consider NTM as potential pathogens. We also discuss the possible mechanisms responsible for the specific relationship between carcinoid tumor and TNM.

Nontuberculous mycobacteria.

Nontuberculous mycobacteria.

Nontuberculous mycobacterial pulmonary infection in patients with cystic fibrosis: diagnosis and treatment.

The prevalence of nontuberculous mycobacteria (NTM) recovered from patients with cystic fibrosis (CF) appears to be increasing, probably related to improved surveillance and microbiological procedures and an increase in the life expectancy of patients with CF. The distinction between active lung infection and colonization is often difficult to assess in patients with CF because of the marked overlap in the clinical and radiological presentation of CF lung disease and lung disease caused by NTM infection. The possibility of active NTM lung infection should be considered in those patients with compatible radiographic changes and/or progressive deterioration in lung function who do not improve with specific antibiotic therapy and who have repeatedly positive sputum cultures and smears for NTM. Patients with repeatedly positive results of acid-fast smears are more likely to be infected than colonized. Pseudomonas overgrowth may confuse the results of sputum and bronchoalveolar lavage fluid cultures. Decontamination of respiratory samples from patients with CF with 5% oxalic acid results in improved bacteriological recovery of NTM. Skin tests are of limited value as a screening tool for NTM. Since the course of NTM lung infection is often slow, careful follow-up with repeated sputum cultures, chest radiographs and computed tomography (CT) scans may be needed. Treatment of NTM lung disease in patients with CF presents great difficulties because of abnormal gastrointestinal drug absorption and pharmacokinetics in this patient population. Treatment varies according to the mycobacterial species isolated. Long-term multidrug regimens including rifampin (rifampicin) and ethambutol are usually required. Monitoring serum drug levels is a useful indicator of correct dosage in order to prevent adverse effects due to potential drug interactions and altered pharmacokinetics in patients with CF.

Clinical evaluation of Amplicor Mycobacterium detection system for the diagnosis of pulmonary mycobacterial infection using sputum

Setting: The Amplicor Mycobacterium detection kit was evaluated for the diagnosis of active pulmonary mycobacterial infection using sputum.Objective: To assess the clinical usefulness of the Amplicor Mycobacterium kit for the diagnosis of pulmonary tuberculosis and non-tuberculous mycobacterial infection in the country of medium prevalence.Design: All the patients were diagnosed with bacterial, histopathological, and clinical ‘gold standard’. The sensitivity and specificity for diagnosing clinically active pulmonary tuberculosis and Mycobacterium avium and Mycobacterium intracellulare infections were evaluated comparing Amplicor results and clinical diagnosis.Results: A total of 1088 sputum specimens were collected from 780 in and out patients. Mycobacteria were recovered from 339 specimens by culture. The sensitivity and specificity of conventional culture method for the diagnosis of pulmonary tuberculosis were 60.2% and 99.8% respectively based on the number of patients. The figures for Amplicor were 61.8% and 97.4% respectively. There was no statistical significant difference between these methods. In rapidity, the Amplicor was significantly superior to the microscopy method in sensitivity.Conclusion: Patients with Amplicor positive and conventional negative result had mostly mycobacteria related diseases. The Amplicor positive result indicated mostly active mycobacterial infection and was clinically useful for rapid diagnosis.

534 Multiple immunophenotypic abnormalities in patients with pulmonary nontuberculous mycobacterial infections

534 Multiple immunophenotypic abnormalities in patients with pulmonary nontuberculous mycobacterial infections

Mycobacterium tuberculosis Versus Nontuberculous Mycobacterial Infection of the Lung in AIDS Patients: CT and HRCT Patterns

The aim of this study was to determine discriminating CT and HRCT features between mycobacterial pulmonary tuberculosis and nontuberculous mycobacterial (NTMB) pulmonary infections in patients with AIDS. CT and HRCT scans of 52 AIDS patients with culture-proven mycobacterial infection [29 with Mycobacterium tuberculosis (MTB) and 23 with NTMB] without concomitant pulmonary infection were reviewed by two observers. Nodular opacities, mainly centrilobular in distribution, were the most common finding, seen in 21 (72%) and 15 (65%) of patients with MTB and NTMB, respectively. A lower lobe predominance of centrilobular nodules was seen more commonly in NTMB (p < 0.03). Ground-glass attenuation was seen in 5 (17%) and 11 (48%) of patients with MTB and NTMB, respectively (p = 0.03). Ground-glass opacities and bronchial wall thickening affected a larger number of lobes in NTMB (p < 0.01), while centrilobular nodules involved more lobes in MTB (p < 0.01). A higher prevalence of unilateral lung involvement was seen in MTB (12 patients, 44%) than NTMB (1 patient, 5%) (p < 0.01). Enlarged lymph nodes were more frequent in patients with MTB than in those with NTMB (22, 76% vs. 10, 43%, respectively) (p < 0.02). NTMB infection and pulmonary tuberculosis display different CT and HRCT patterns in AIDS patients, but there is considerable overlap in CT findings.

Comparison of characteristics of patients and treatment outcome for pulmonary non-tuberculous mycobacterial infection and pulmonary tuberculosis.

Patients with non-tuberculous mycobacteria are usually started on conventional antituberculous triple therapy once acid fast bacilli are detected, before the exact type of mycobacteria has been identified. The ability to identify the characteristics of patients with tuberculous and non-tuberculous mycobacteria may be helpful in identifying before treatment those patients more likely to have non-tuberculous infection. A retrospective study was conducted of all patients in one unit in whom non-tuberculous mycobacteria were identified in sputum or bronchoalveolar washings in the period 1987-93. The pattern of drug resistance was determined from laboratory records, and all case notes and chest radiographs were reviewed to identify the underlying disease and treatment outcome. All cases were compared with a matched control group of patients with culture positive Mycobacterium tuberculosis diagnosed during the same period. In the period studied there were 70 non-tuberculous and 221 tuberculous isolates. The non-tuberculous bacteria were typed as follows: M xenopi 23 (33%), M kansasii 19 (27%), M fortuitum 14 (20%), others 14 (20%). Of those with non-tuberculous mycobacteria, 83% were white subjects compared with 47% for tuberculosis. Patients with non-tuberculous mycobacteria were older than those with tuberculosis. Pre-existing lung disease or AIDS was present in 81% of patients with non-tuberculous mycobacteria and in 17% of patients with tuberculosis. Sensitivity to rifampicin and ethambutol was seen in 95% of M xenopi and 96% of M kansasii isolates. Relapse occurred in 60% of cases infected with M xenopi, 20% infected with M kansasii, and in 7% of cases with tuberculosis. In the population studied non-tuberculous mycobacteria occurred most frequently in elderly white subjects with pre-existing lung disease. If mycobacteria are detected in this group, consideration should be given to the possibility of non-tuberculous infection before embarking on treatment. A combination containing rifampicin and ethambutol is effective. The relapse rate for infection with M xenopi is high and prospective studies of the effect of the above combination of antituberculosis drugs are needed.

Spectrum of pulmonary nontuberculous mycobacterial infection.

To organize pulmonary nontuberculous mycobacterial (NTMB) infections into a classification system based on clinical and radiographic features. Scientific literature was reviewed and organized into a framework of clinical-radiographic syndromes of NTMB infection. NTMB infection was classified into five clinical-radiographic syndromes. The "classical" form radiographically mimics tuberculosis. It is seen predominantly in white male patients with underlying chronic obstructive lung disease. "Nonclassical" disease radiographically appears as nodular infiltrates and bronchiectasis in a sporadic distribution. It characteristically occurs in elderly women without underlying chronic illness. Asymptomatic nodules are another manifestation. Immunocompromised individuals develop disseminated infection, often with few or no pulmonary symptoms but various chest radiographic manifestations. Patients with achalasia have a radiographic appearance that most often resembles aspiration pneumonia. Most pulmonary NTMB infections can be classified into one of five categories, which helps in the understanding of these wide-ranging manifestations.

Surgical management of resistant Mycobacterial tuberculosis and other mycobacterial pulmonary infections

Between August 1983 and October 1990, 42 patients with resistant Mycobacterium tuberculosis underwent 44 pulmonary resections. During the same time, 38 patients with mycobacterial infections other than tuberculosis had 41 pulmonary resections. All patients either were poor candidates for medical therapy alone or had existing complications requiring surgical intervention. There was one operative death in each group, both from adult respiratory distress syndrome (postpneumonectomy pulmonary edema). Complications were high, with bronchopleural fistula most commonly occurring after right pneumonectomy in patients infected with Mycobacterium avium with superimposed infection with nonmycobacterial pathogens. In patients undergoing pneumonectomy for resistant Mycobacterium tuberculosis, the left lung was most often resected. It is recommended that if localized disease is present and medical treatment is likely to fail, pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection after 3 months of drug-specific therapy. Muscle flaps were used frequently to avoid residual space and bronchial stump problems. Earlier resection in patients with indolent nontuberculous mycobacterial pulmonary infections is advocated before extensive polymicrobial contamination and right lung destruction.