Pulmonary Nontuberculous Mycobacterial Research Articles

Clinical Analysis of Patients with Pulmonary Nontuberculous Mycobacterial Disease Complicated by Pneumothorax

We clarified the clinical characteristics of patients with pulmonary nontuberculous mycobacterial (NTM) disease complicated by pneumothorax. We retrospectively selected 220 patients who satisfied the diagnostic criteria for NTM disease proposed by the American Thoracic Society (ATS). Nine patients with pulmonary NTM disease were complicated with pneumothorax. We investigated the patients' background, laboratory findings, radiological findings, treatment and prognoses. There were nine patients, including six men and three women, with a mean age of 73.2 years. Seven patients had underlying respiratory diseases such as chronic obstructive pulmonary disease (COPD) excluding pulmonary NTM disease. The causative microorganisms was Mycobacterium avium in four patients, M. intracellulare in four patients, and M. kansasii in one patient. Regarding the radiological findings, pneumothorax was recognized in the right lung in five patients, in the left lung in three patients, and in both lungs heterogeneously in one patient. Although most patients exhibited multiple cavities and extensive lesions over the unilateral lung fields, three patients were simultaneously diagnosed with pulmonary NTM disease at the onset of pneumothorax. As for treatment, thoracic drainage was performed in seven patients, while one patient was advised only to rest and one patient required both thoracic drainage and surgery. The responses to the treatment was poor in each case, and five patients died due to pneumonia or heart failure. In this study, the rate of pneumothorax complications in the patients with pulmonary NTM disease (4.1%) was higher than that of other reports. The responses to treatment, and prognoses were poor due to the presence of other complications.

Pulmonary Mycobacterium abscessus disease in a patient receiving low-dose methotrexate for treatment of early rheumatoid arthritis

A 70-year-old woman with methotrexate (MTX)-refractory rheumatoid arthritis (RA) was referred to our hospital for introduction of biological therapy. On high-resolution computed tomography scans, the patient exhibited abnormal findings such as bronchiectasis and centrilobular small nodules, which were highly suggestive of pulmonary nontuberculous mycobacterial (NTM) disease. Although mycobacterial cultures of sputum specimens yielded negative results, cultures of bronchoalveolar lavage fluids grew Mycobacterium abscessus. Frequent follow-up chest radiographs indicated that the patient's pulmonary disease became rapidly worse in 1month following dose escalation of MTX and administration of low-dose prednisolone. Oral clarithromycin and levofloxacin, chosen on the basis of in vitro susceptibility testing, led to a dramatic recovery from this potentially life-threatening complication. Through our experience with this case, we have learned that (1) pulmonary M. abscessus disease can progress rapidly, even during nonbiological anti-RA therapy; (2) regular follow-up chest radiographs are useful to ensure timely implementation of anti-NTM treatment; (3) bronchoscopic testing should be considered when patients are suspected of pulmonary NTM disease but do not meet the diagnostic criteria; and (4) early isolation, identification, and susceptibility testing of causative NTM species are critical for favorable outcomes.

Mixed Pulmonary Infection with Three Types of Nontuberculous Mycobacteria

A 71-year-old man with a history of chronic obstructive pulmonary disease (COPD) and silicosis was referred to our hospital for an evaluation of dyspnea. A progressively enlarging cavity found in the patient's left lower lung was associated with a worsening respiratory status. One year after the initial referral, the patient was diagnosed with nontuberculous mycobacterial (NTM) infection. We herein report the case of a patient with a mixed infection of M. kansasii, M. avium complex and M. abscessus, the various organisms having been isolated in succession. Recognizing a diagnosis of mixed pulmonary NTM infection is therefore crucial in patients with underlying diseases.

Spatial Clusters of Nontuberculous Mycobacterial Lung Disease in the United States

Prevalence of pulmonary nontuberculous mycobacterial (PNTM) disease varies by geographic region, yet the factors driving these differences remain largely unknown. To identify spatial clusters of PNTM disease at the county level and to describe environmental and sociodemographic factors predictive of disease. PNTM cases identified from a nationally representative sample of Medicare Part B beneficiaries from 1997 to 2007 were geocoded by county and state of residence. County-level PNTM case counts and Medicare population data were then uploaded into SaTScan to identify significant spatial clusters and low-risk areas of disease. High-risk and low-risk counties were then compared to identify significant sociodemographic and environmental differences. We identified seven significant (P < 0.05) clusters of PNTM cases. These high-risk areas encompassed 55 counties in 8 states, including parts of California, Florida, Hawaii, Louisiana, New York, Oklahoma, Pennsylvania, and Wisconsin. Five low-risk areas were also identified, which encompassed 746 counties in 23 states, mostly in the Midwest. Counties in high-risk areas were significantly larger, had greater population densities, and higher education and income levels than low-risk counties. High-risk counties also had higher mean daily potential evapotranspiration levels and percentages covered by surface water, and were more likely to have greater copper and sodium levels in the soil, although lower manganese levels. Specific environmental factors related to soil and water exposure appear to increase the risk of PNTM infection. Still, given that environmental sources of NTM are ubiquitous and PNTM disease is rare, both host susceptibility and environmental factors must be considered in explaining disease development.

Is continuation of anti-tumor necrosis factor-α therapy a safe option for patients who have developed pulmonary mycobacterial infection?

Continuation of anti-tumor necrosis factor-α (TNFα) therapy generally has not been recommended for patients who have developed nontuberculous mycobacterial (NTM) diseases; in daily practice, however, we often encounter patients with refractory rheumatoid arthritis (RA) who experience uncontrollable flares following withdrawal of anti-TNFα agents. Here, we report a case of pulmonary NTM disease caused by Mycobacterium intracellulare occurring in a patient with refractory RA undergoing etanercept therapy. Since there was the concern of an exacerbation of RA symptoms, etanercept was continued during anti-NTM therapy. The patient's pulmonary symptoms and radiological abnormalities were found to have markedly improved in a relatively short time period after beginning the anti-NTM therapy. Additionally, her RA symptoms were adequately controlled without the occurrence of any unexpected adverse events. The continuation of etanercept therapy may be a safe option during anti-NTM therapy if patients' underlying diseases would otherwise be difficult to control. Strictly supervised anti-NTM therapy and patients' informed consent are mandatory. We review the medical literature on NTM disease associated with anti-TNFα therapy for rheumatic diseases and discuss the safety of simultaneous use of anti-TNFα agents in patients during anti-NTM therapy.

Nontuberculous mycobacterial infections in cancer patients in a medical center in Taiwan, 2005–2008

Data on the nontuberculous mycobacterial (NTM) species that cause infection and the characteristics of disease caused by these pathogens in cancer patients are limited, so we perform this study to investigate the species distribution of NTM isolates from various clinical specimens and to elucidate the epidemiologic trends in NTM isolates and diseases among cancer patients. From 2005 through 2008, cancer patients with NTM infections as defined by the American Thoracic Society/Infectious Diseases Society of America criteria were identified at the National Taiwan University Hospital. The medical records of all patients were reviewed. During the study period, a total of 219 cancer patients with NTM infections were identified. Among them, 133 (60.7%) patients were older than 65 years, most of whom were men. Lung cancer was the most common type of cancer, followed by hematologic cancer and gastrointestinal tract cancer. Pulmonary NTM infection was the most common type of infection in 205 (93.6%) patients, followed by skin and soft tissue infections ( n = 7, 3.2%), disseminated infections ( n = 4, 1.8%), and genitourinary tract infection ( n = 3, 1.4%). Disseminated infections occurred exclusively in patients with hematologic cancer. Mycobacterium avium complex (MAC) caused the majority of pulmonary NTM infections in cancer patients; in contrast, M. abscessus was the most common causative pathogen of extrapulmonary NTM diseases, followed by MAC. In conclusion, physicians need to be aware of the possibility of co-existing pulmonary NTM infection in patients with lung cancer. In addition, disseminated NTM infection should be considered in patients with hematologic cancer.

The role of gallium-67 scintigraphy in comparing inflammatory activity between tuberculous and nontuberculous mycobacterial pulmonary diseases

The purpose of this study was to compare the inflammatory activity of pulmonary lesions between active tuberculosis and nontuberculous mycobacterial (NTM) infection in acid-fast bacilli smear-positive non-HIV-infected patients using gallium-67 (Ga) scintigraphy. Twenty-four patients with culture-proven active pulmonary tuberculosis (PTB) and an additional 17 patients meeting the criteria of pulmonary NTM infection were enrolled into the retrospective study. The Ga uptake of the pulmonary lesion was assessed by visual scoring of uptake grade and semiquantitative region of interest analysis of the uptake ratio using the thoracic spine as a reference. Ga scans were positive in 23 of the 24 patients (95.8%) with PTB and in 12 of the 17 patients (70.6%) with pulmonary NTM infection. Twenty patients with active PTB had moderate or intense visual Ga uptake grade, whereas only three patients with pulmonary NTM infection had moderate visual Ga uptake grade. The semiquantitative pulmonary Ga uptake ratios in patients with active PTB and NTM infection were 1.17 ± 0.28 (range: 0.77-1.86) and 0.79 ± 0.12 (range: 0.60-1.03), respectively. The Ga uptake grade and ratio of active PTB were both significantly higher than NTM infection (both P < 0.001). In the receiver operating characteristic curve analysis for predicting active PTB, the area under the curves of Ga uptake grade and ratio were 0.90 ± 0.05 and 0.93 ± 0.04, respectively (both P < 0.001). The inflammatory activity of active PTB is significantly higher than that of pulmonary NTM infection in non-HIV-infected patients. Ga uptake grade and ratio could be used to predict active PTB in acid-fast bacilli smear-positive patients.

Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality

Pulmonary non-tuberculous mycobacterial (NTM) infection is relatively common after lung transplantation, but the effect on mortality remains undetermined. Herein we describe our experience with pulmonary NTM infection after lung transplantation and hypothesized that non-tuberculous mycobacterial infection after lung transplantation would be associated with increased mortality. We retrospectively evaluated 201 primary lung transplant recipients transplanted between January 2000 and August 2006. Serial bronchoscopies with bronchoalveolar lavage and transbronchial biopsy were performed according to a surveillance protocol and when clinically indicated. The diagnosis NTM infection was established by a positive NTM culture in a bronchoalveolar lavage sample or in at least two separate expectorated sputum samples. NTM infections were further classified as "disease" or "colonization," based on whether or not NTM infection patients developed symptoms and characteristic radiographic findings. Thirty-six (18%) recipients were diagnosed with pulmonary NTM infection at a median of 97 days post-transplantation: 9 were classified as NTM disease and the remaining 27 as NTM colonization cases. Single lung transplant was a significant risk factor for NTM infection (HR 2.25, p = 0.02). NTM colonization was a risk factor for NTM disease (HR 8.39, p = 0.003). NTM infection significantly increased the risk of death after lung transplantation (HR 2.61, p = 0.001) and persisted in multivariate models controlling for single lung transplant and bronchiolitis obliterans syndrome. The increased risk was seen for both NTM colonization and NTM disease. Among the patients who died, non-NTM infection was a more common contributing factor in the cause of death for the NTM infection group (44% vs 12%, p = 0.04). Non-tuberculous mycobacterial infection is common after lung transplantation. NTM colonization and treated acute rejection are risk factors for NTM disease. NTM infection is associated with increased risk of mortality independent of bronchiolitis obliterans syndrome.

Lady Windermere revisited: treatment with thoracoscopic lobectomy/segmentectomy for right middle lobe and lingular bronchiectasis associated with non-tuberculous mycobacterial disease☆

Lady Windermere syndrome is a well-known but poorly understood female predominant phenotype of isolated right middle lobe and lingular bronchiectasis associated with non-tuberculous mycobacterial (NTM) infection. Despite lengthy multidrug antibiotic treatment, the presence of damaged parenchymal tissue leads to symptomatic disease recurrence, often with resistant organisms. The use of surgical resection as an adjunct to medical therapy may alter this cycle, although little is known about the use of thoracoscopic lung resection in this patient population. This is a retrospective review of a prospectively collected database of patients with pulmonary NTM disease from July 2004 to December 2009. All patients had focal bronchiectasis of the right middle lobe and lingula, treated with targeted antimicrobial therapy for several months prior to resection. A total of 134 patients underwent 172 operations, with 38 patients having staged bilateral resections. The cohort was predominately female (96%) and Caucasian (95%), with a mean age of 59 years (range 34-81 years). Using a thoracoscopic approach in all patients, 102 middle lobectomies and 70 lingulectomies were performed. Conversion to open thoracotomy occurred in five cases (3%). Secondary procedures were performed in 20 cases (12%). There was no operative mortality. Postoperative morbidity was noted following 12 operations (7%), primarily consisting of prolonged air leak. The mean length of stay was 3.3 days (range 1-15 days). Although medical therapy remains the primary treatment modality for patients with pulmonary NTM disease, the selective use of pulmonary resection may reduce the incidence of symptomatic disease recurrence. The addition of thoracoscopic resection to treatment regimens for patients with Lady Windermere syndrome can be accomplished with minimal morbidity and mortality.

Nontuberculous mycobacteria: opportunistic environmental pathogens for predisposed hosts

Nontuberculous mycobacterial (NTM) infections are caused by environmental mycobacteria. Patients with pulmonary NTM disease usually have predisposing lung abnormalities. Diagnostic methods are evolving. Treatment is largely empiric. Data were extracted from peer reviewed publications, guidelines, and case series. Progressive NTM lung disease should be treated. Multidrug regimens are mostly macrolide based and are occasionally complemented by lung resection. Disease persistence and relapse are not uncommon and are a greater problem with so-called rapid-grower NTM infections. Some of the issues considered in this review are: the role of antibiotic susceptibility testing in predicting treatment effectiveness, optimal drug combinations, daily vs. intermittent dosing intervals for different NTM infections and disease severity, when the goal of cure should be replaced with observation or palliation, and patient selection for surgery. Future needs for development and research include improved epidemiology, definition of genetic and other risk factors, definition of predictors of treatment outcome, multicenter treatment studies, new drug discovery and animal models of disease and treatment.

Nontuberculous Mycobacterial Lung Infections in Ontario, Canada: Clinical and Microbiological Characteristics

The aim of this study was to determine gender and clinical phenotype frequencies in pulmonary nontuberculous mycobacterial (NTM) infection and the frequency of disease in NTM isolates. The study is a retrospective observational cohort study of two overlapping cohorts: population cohort and clinical cohort. Setting The study was conducted at the University Health Network and Ontario Mycobacteriology Laboratory in Toronto, Ontario, Canada. The population cohort consisted of all patients with one or more pulmonary NTM isolates in Ontario in 2003. The clinical cohort consisted of all patients with one or more pulmonary NTM isolates at our hospital in 2002-2003. Interventions The study entailed the review of laboratory records and demographics (both cohorts) and detailed clinical records (clinical cohort). In the population cohort (N = 1651), females comprised 48% overall and 51% with microbiological disease criteria. In the clinical cohort (N = 552), females comprised 48% overall and 55% with NTM disease. In the population cohort, 45% fulfilled microbiological disease criteria, and in the clinical cohort 46% of patients had disease. Patients with MAC isolates fulfilled microbiological disease criteria in 51% of population cohort cases and all disease criteria in 52% of clinical cohort cases. Women more commonly fulfilled microbiological disease criteria in the population cohort (51 vs. 45%, P = 0.02) and all disease criteria in the clinical cohort (53 vs. 40%, P = 0.03). Among clinical cohort patients, 26% (13 women, 44 men) had fibrocavitation, while 62% (101 women, 37 men) had nodular bronchiectasis. Women comprised a small majority with disease. Nodular bronchiectasis in women was most common, but significant proportions of each gender with each radiographic type were observed. NTM isolation, particularly MAC, was frequently associated with disease.

Pulmonary Nontuberculous Mycobacterial Disease

Pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but predisposing features have been elusive. To prospectively determine the morphotype, immunophenotype, and cystic fibrosis transmembrane conductance regulator genotype in a large cohort with PNTM. We prospectively enrolled 63 patients with PNTM infection, each of whom had computerized tomography, echocardiogram, pulmonary function, and flow cytometry of peripheral blood. In vitro cytokine production in response to mitogen, LPS, and cytokines was performed. Anthropometric measurements were compared with National Health and Nutrition Examination Survey (NHANES) age- and ethnicity-matched female control subjects extracted from the NHANES 2001-2002 dataset. Patients were 59.9 (+/-9.8 yr [SD]) old, and 5.4 (+/-7.9 yr) from diagnosis to enrollment. Patients were 95% female, 91% white, and 68% lifetime nonsmokers. A total of 46 were infected with Mycobacterium avium complex, M. xenopi, or M. kansasii; 17 were infected with rapidly growing mycobacteria. Female patients were significantly taller (164.7 vs. 161.0 cm; P < 0.001) and thinner (body mass index, 21.1 vs. 28.2; P < 0.001) than matched NHANES control subjects, and thinner (body mass index, 21.1 vs. 26.8; P = 0.002) than patients with disseminated nontuberculous mycobacterial infection. A total of 51% of patients had scoliosis, 11% pectus excavatum, and 9% mitral valve prolapse, all significantly more than reference populations. Stimulated cytokine production was similar to that of healthy control subjects, including the IFN-gamma/IL-12 pathway. CD4(+), CD8(+), B, and natural killer cell numbers were normal. A total of 36% of patients had mutations in the cystic fibrosis transmembrane conductance regulator gene. Patients with PNTM infection are taller and leaner than control subjects, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and cystic fibrosis transmembrane conductance regulator mutations, but without recognized immune defects.

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.

Nontuberculous mycobacteria: defining disease in a prospective cohort of South African miners.

A gold mining work force was followed prospectively over 1 yr for sputum nontuberculous mycobacterial (NTM) isolates. NTM were isolated from 118 men, of whom 32 (27%) met the American Thoracic Society (ATS) case-definitions for pulmonary NTM disease (23 M. kansasii, seven M. scrofulaceum, one M. avium, and one M. abscessus). Determining isolate significance was difficult because most men had been started on presumptive TB treatment before isolate identification (70%). Histologic criteria were considered inappropriate for this high M. tuberculosis incidence population, particularly for patients who had stabilized on presumptive TB treatment. Among men not meeting case-definitions, indicators of disease were significantly more prevalent for M. kansasii than for M. fortuitum, the local laboratory contaminant (ORs: 6.5 for cough, 7. 2 for smear-positivity, 36.0 for radiologic changes, and 14.3 for presumptive TB treatment), suggesting underdiagnosis of M. kansasii disease. Of 53 men with definite or possible M. kansasii disease, 18 (34%) were HIV-positive. HIV-associated M. kansasii disease occurred at an early stage of immunosuppression (median CD4 count, 381 x 10(6)/L) with a good outcome (83% cured after 12 mo of treatment). ATS case-definitions for NTM disease are difficult to apply in this population, and treatment decisions should be guided by the pathogenic potential of the isolate.

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.