Clinical Aspects of Pulmonary Nontuberculous Mycobacteriosis

Nontuberculous mycobacterial (NTM) infections are an emerging problem. Common organisms include Mycobacterium avium, M. intracellulare, and M. kansasii, along with the M. avium intracellulare complex (MAC), which includes both M. avium and M. intracellulare. Typically, NTM infections affect the lungs and subsequently demonstrate a chronic course. Therefore, persistent respiratory symptoms generally indicate of the presence of pulmonary NTM diseases, and chest radiography, along with a sputum examination, are essential for its diagnosis. Because NTM are ubiquitous environmental organisms, a positive culture from a minimum of two separate expectorated sputum samples are required to make a diagnosis. The repertoire of effective drugs for treatment is considerably limited, indicating the need for long-term management with multiple drugs. Establishing a treatment regimen with high therapeutic efficacy and safety is an important issue for the future.     

Regional differences of nontuberculous mycobacteria species in Ulsan,Korea

Background

In Korea recently, nontuberculous mycobacteria (NTM) have been more frequently isolated in respiratory specimens, while Mycobacterium tuberculosis (MTB) isolations have decreased. The major NTM lung disease species in Korea are M. intracellulare, M. avium, and M. abscessus, whereas M. kansasii is a rare species. This retrospective study was performed to determine if there are region-specific characteristics of lung disease-causing NTM species in Ulsan, a highly industrialized city in Korea.

Methods

Between January 2010 and July 2013, the results of all acid-fast bacilli (AFB) cultures of respiratory specimens performed at Ulsan University Hospital (Ulsan, Korea) were collected. NTM were identified and regional differences of NTM species were compared.

Results

AFB cultures were performed on 33,567 respiratory specimens, obtained from 10,208 patients, during the study period. Further, 10% of the specimens (3,287/33,567) were AFB culture-positive [MTB, 2,288/3,287 (70%); NTM 999/3,287 (30%)]. The proportion of NTM isolations gradually increased between 2010 and 2013, at 25% and 38%, respectively. The most common NTM species was M. intracellulare (356/999, 36%), followed by M. kansasii (295/999, 30%), M. avium (161/999, 16%), M. abscessus (117/999, 12%) and M. fortuitum (39/999, 4%). This trend was maintained throughout the study period.

Conclusions

In Ulsan, NTM isolation from respiratory specimens is increasing, consistent with previous studies performed in Korea. The distribution of respiratory NTM species, however, differed from previous studies that were performed in other regions of Korea: M. kansasii was the second most common NTM species in Ulsan. In Ulsan, there is a regional difference in the NTM species isolated.     

Life-threatening Mycobacterium intracellulare pleuritis in an immunocompetent host: Case reports

Rationale:Nontuberculous mycobacteria (NTM)–associated pleuritis is a very rare disease. Here, we describe 2 cases of life-threatening Mycobacterium intracellulare-associated pleuritis in immunocompetent hosts.Patient concerns:A 78-year-old man with sudden onset-onset dyspnea (case 1) and an 80-year-old man with cough, sputum and fever (case 2) presented to our emergency room.Diagnoses:Both the patients were diagnosed with Mycobacterium intracellulare-associated pleuritis.Intervention:In case 1, the patient underwent intubation with mechanical ventilation due to hypoxemic respiratory failure. Daily azithromycin, rifampin and ethambutol, and intravenous amikacin 3 times a week was administered. In case 2, the patient received daily azithromycin, rifampin and ethambutol, and intravenous amikacin 3 times a week.Outcomes:In case 1, after receiving NTM treatment for 14 months, NTM-associated pleuritis was cured, with radiologic improvement. In case 2, however, bronchopleural fistula was developed. Despite tube drainage, air leak continued. The patient refused surgical management and eventually died of respiratory failure.Lessons:Pleural effusion arising from NTM lung disease located in the subpleural area should be considered a possible cause of NTM-associated pleuritis. Drainage and a multidrug regimen are required to treat NTM, and surgical treatment should be considered when complications occur.     

Mycobacterium avium‐intracellulare‐associated acute interstitial nephritis: a rare cause of renal allograft dysfunction

Abstract: Nontuberculous mycobacterium (NTM) infections are unusual in the renal transplant population. We present a case of disseminated Mycobacterium avium‐intracellulare in a renal transplant recipient who was negative for human immunodeficiency virus infection. Our patient developed renal allograft dysfunction in the setting of disseminated disease and reduced immunosuppression. Transplant biopsy showed acute interstitial nephritis with granulomas and acid‐fast bacilli. Acute renal failure resolved completely with further reductions in immunosuppression and anti‐mycobacterial therapy. Our patient demonstrates the challenges in diagnosis and treatment of this rare infectious complication.     

Identification and characterization of nontuberculous mycobacteria isolated from suspected pulmonary tuberculosis patients in eastern china from 2009 to 2019 using an identification array system

ObjectiveNontuberculous mycobacteria (NTM) species are increasingly being isolated and have become a key factor affecting public health by causing pulmonary diseases. Most NTM species do not respond to conventional tuberculosis (TB) drugs. This study aimed to identify NTM isolated from suspected pulmonary TB patients from the Zhejiang province and analyze their distribution in the region.MethodsA total of 1,113 NTM isolates from patients suspected to be suffering from acid-fast bacilli-positive tuberculosis were identified at the species level, using the CapitalBio Mycobacterium identification array and polymerase chain reaction amplification and sequencing of 16S-23S gene internal transcribed spacer (ITS), 16S rRNA, and hsp65.ResultsOf the 23,138 isolates, we identified 1,102 NTM (4.8%), mainly including Mycobacterium intracellulare (54.81%, 604/1,102), M. chelonae-M. abscessus (16.52%, 182/1,102), M. avium (13.16%, 145/1,102), M. kansasii (8.17%, 90/1,102), and M. gordonae (3.27%, 36/1,102).ConclusionThe distribution of NTM species observed in patients with suspected pulmonary tuberculosis provides guidance for the diagnosis and treatment of NTM pulmonary diseases.     

Increased risk of nontuberculous mycobacterial infection in asthmatic patients using long-term inhaled corticosteroid therapy

Background and objective: The risk of pneumonia is increased among COPD patients using inhaled corticosteroids (ICS). However, there is uncertainty regarding the association between long‐term use of ICS and exacerbations of respiratory tract infections among asthmatic patients. Methods: A case‐control nested cohort study was performed to assess the association of asthma with nontuberculous mycobacterium (NTM) infection. Results: Among this cohort of 464 asthmatic patients, 14 experienced complications due to NTM infections, of which eight were caused by Mycobacterium avium‐intracellulare complex, three by M. kansasii, one by M. terrae and the remaining two by unclassifiable scotochromogens. Asthmatic patients with NTM infections were older (67.1 ± 8.6 vs 58.8 ± 12.3 years, P < 0.01) and had more severe airflow limitation (FEV₁%, 60.6 ± 10.3 vs 72.3 ± 18.3, P < 0.03) than those without NTM infections. All except one had received ICS treatment for more than 5 years, and 12 of the 14 patients used inhaled fluticasone propionate daily (four patients at a dose of 400 µg/day and eight patients at a dose >800 µg/day). Conclusions: These findings suggest that the risk of NTM infection may be greater in asthmatic patients who are older, have more severe airflow limitation and receive higher doses of ICS therapy.     

Epidemiologie der nichttuberkul?sen mykobakteriellen Erkrankungen in Deutschland und weltweit

Nontuberculous mycobacterial (NTM) lung disease is by far the most common NTM disease. Clinically important are NTM lymphadenitis in children, immune reconstitution syndrome in HIV patients, and NTM skin disease, mostly as fish tank granuloma due to M.?marinum. In contrast to M.?tuberculosis, NTM are not spread from human to human and exposure to NTM from the environment does not per se lead to infection and disease, explaining the few epidemiological data and published studies. New data, however, show that NTM lung disease prevalence has been increasing in North America since the mid1990s; in northwestern Europe the limited published data suggest a lower, but also increasing incidence that differs by region. The incidence of NTM cervicofacial lymphadenitis (1/100,000 children) is highest in children under 4?years of age; however, data represent only microbiologically confirmed cases. Factors underlying the changing and differing epidemiology are discussed. The English full-text version of this article is available at SpringerLink (under ??Supplemental??).     

Elevated serum CA‐125 levels in patients with non‐tuberculous mycobacterial lung disease

Background and objective: Although cancer antigen 125 (CA‐125) is a useful marker for the diagnosis of ovarian cancer, CA‐125 levels are elevated in many benign conditions, including tuberculosis (TB). The clinical significance of serum CA‐125 measurements in patients with non‐tuberculous mycobacterial (NTM) lung disease was evaluated. Methods: Patients with NTM lung disease (n = 53), in whom serum CA‐125 levels had been measured, were retrospectively enrolled in the study. Twenty‐eight patients with pulmonary TB were included as a comparison group. Clinical, radiological and bacteriological parameters were assessed according to serum CA‐125 status. Results: Among 53 patients with NTM lung disease, serum CA‐125 levels were elevated in 28 (52.8%), and this proportion was not significantly different from that of the TB patients (44.8%). Cavitation and upper lobe cavitary type disease were more frequent in NTM patients with elevated serum CA‐125 levels compared with those without increased CA‐125 levels (P < 0.05 for both). The clinical course of NTM lung disease was correlated with changes in serum CA‐125 levels. Conclusions: Serum CA‐125 levels were increased in significant proportions of NTM patients, as well as TB patients. Further studies are needed to investigate the usefulness of serum CA‐125 measurements in patients with NTM pulmonary disease.     

Biomarker for nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis: Anti-glycopeptidolipid core antigen immunoglobulin A antibodies

Objective: Nontuberculous mycobacterial (NTM) pulmonary disease is occasionally associated with rheumatoid arthritis (RA), influencing the therapeutic strategy of RA. Since chronic lung diseases are frequently associated with RA, the diagnosis of NTM pulmonary disease is quite difficult in RA patients. Recently, a serological diagnostic test detecting serum immunoglobulin A against the glycopeptidolipid (GPL) core antigen was developed. We investigated the serum levels of anti-GPL antibodies in RA patients to determine the usefulness for detecting NTM pulmonary disease.

Methods: Anti-GPL antibodies were detected in the sera from RA patients with or without NTM pulmonary disease.

Results: The positivity of anti-GPL antibodies in RA patients with NTM pulmonary disease was higher than in RA without (p?=?1.76?×?10^?14, odds ratio 70.29, 95% confidence interval [CI] 22.28–221.83). Anti-GPL Ab titers were increased in RA with NTM pulmonary disease (mean titer?±?standard deviation [U/ml], RA with NTM pulmonary disease: 4.1?±?7.0, RA without NTM pulmonary disease: 0.4?±?1.6, p?=?1.51?×?10^?10). The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for anti-GPL antibodies was 0.917 (95%CI 0.860–0.974, p?=?3.32?×?10^?47).

Conclusions: Serum anti-GPL antibodies are useful for detecting NTM pulmonary disease in RA patients.     

1例长期机械通气并发非结核分枝杆菌肺病

目的探讨非结核分枝杆菌肺病的易患因素、临床特点及治疗与转归。方法对1例慢性阻塞性肺疾病(COPD)长期机械通气合并非结核分枝杆菌肺病的病例诊治过程进行回顾,并结合相关文献进行分析。结果患者通过临床症状、影像学表现、痰涂片诊断为分枝杆菌肺病,经DNA微阵列芯片法行菌种鉴定为龟/脓肿分枝杆菌,给予利福平胶囊、乙胺丁醇片、克拉霉素片口服治疗2月,后因机械通气并发气胸死亡。结论非结核分枝杆菌成为呼吸机相关性肺炎致病菌之一,非结核分枝杆菌肺病多发生在既往有结构性肺病或者细胞免疫功能低下的患者,难以治愈、并发症多,及早诊断是治疗关键。     

Clinical and pathological characteristics of mycobacterial tenosynovitis and arthritis

Purpose

To investigate the clinical characteristics and pathological features of patients with mycobacterial tenosynovitis and arthritis.

Methods

All patients with tenosynovitis and arthritis caused by Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM) who were treated at a medical center in Taiwan from 2001 to 2010 were analyzed.

Results

Thirty-two patients with mycobacterial tenosynovitis and arthritis were identified. MTB was isolated exclusively from patients with arthritis of large joints (n = 11), while NTM were isolated from patients with arthritis of large joints (n = 4) and from those with tenosynovitis (n = 17). Among patients with tenosynovitis due to NTM, the most commonly found NTM were M. marinum (n = 7), M. intracellulare (n = 5), and M. abscessus (sensu stricto) (n = 2). Six of the seven patients with tenosynovitis due to M. marinum had suffered fishing-related injuries to the hands. All four patients with NTM arthritis had recurrent septic arthritis after surgery. NTM were isolated once from the debrided tissue specimens in three of these patients; the other patient died of systemic infection caused by M. intracellulare and multiple bacterial pathogens.

Conclusion

Mycobacterial tenosynovitis should be considered in patients who present with indolent symptoms of chronic tenosynovitis. Complete clinical information, including history of trauma or joint replacement surgery and underlying systemic disease, is helpful in establishing an early diagnosis of the disease.     

Chest computed tomography predicts microbiological burden and symptoms in pulmonary Mycobacterium xenopi

Background and objective: The development of computed tomography (CT) findings usually precedes the diagnosis of pulmonary nontuberculous mycobacterial infection. The utility of specific CT scan features, although often available long before respiratory sample cultures, is not fully understood. We sought to assess associations among CT features, symptoms and microbiological disease criteria in pulmonary Mycobacterium xenopi isolation. Methods: We reviewed 70 consecutive immunocompetent patients with pulmonary M. xenopi isolation and classified them according to the American Thoracic Society (ATS) diagnostic criteria for disease. ‘Definite disease’ patients (n = 16) met modified ATS criteria. ‘Possible disease’ patients (n = 10) met microbiological criteria, had abnormal CT scans, but data regarding symptoms were unavailable. ‘No disease’ patients (n = 44) had only one positive sputum culture, or were asymptomatic or had no relevant CT findings. Two radiologists, without knowledge of the clinical or microbiological information, independently reviewed the scans. Results: The mean (standard deviation) age of all patients was 63 (16) years, and 39% were women. Patients with ‘definite disease’ usually had nodules (88%) and cavities (63%), but less often bronchiectasis (50%) and tree‐in‐bud (50%). Patients with ‘possible’ or ‘no disease’, respectively, had nodules (100% or 80%), bronchiectasis (40% or 18%) or tree‐in‐bud (40% or 11%). Cavitation (P ≤ 0.0001) and nodules ≥5 mm (P = 0.0002) were associated with fulfilled microbiological criteria for disease. Bronchiectasis (P = 0.02) and nodules <5 mm (P = 0.002) were associated with symptoms of infection. Conclusions: Among immunocompetent patients with pulmonary M. xenopi isolation, cavitation and large nodules predict fulfilling microbiological disease criteria, while bronchiectasis and small nodules predict symptoms.     

The expanding spectrum of Mycobacterium avium complex-associated pulmonary disease

Nontuberculous mycobacteria (NTM) are increasingly recognized as important pulmonary pathogens. Mycobacterium avium intracellulare complex (MAC) causes most lung infections due to NTM. Patients with preexisting lung disease or immunodeficiency are at greatest risk for developing MAC infection. The majority of MAC pulmonary cases, however, occur in immunocompetent elderly women in association with nodular infiltrates and bronchiectasis. More recently, pulmonary disease has also been described in immunocompetent patients after exposure to MAC-contaminated hot tubs. We describe a case of aggressive MAC lung disease in a young immunocompetent female patient without preexisting lung disease whose clinical and pathologic characteristics do not fit into any of these categories and may represent a unique manifestation of MAC lung disease.     

Decreased Cytokine Production in Patients with Nontuberculous Mycobacterial Lung Disease

Nontuberculous mycobacteria (NTM) are intracellular pathogens that elicit a specific T-cell response characterized by the production of proinflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-12. However, little information exists regarding the levels of specific cytokines in patients with NTM lung disease. Therefore, we compared cytokine production in peripheral blood mononuclear cells (PBMCs) from patients with NTM lung disease with that in PBMCs from healthy controls. Pro- and anti-inflammatory cytokine production was measured by enzyme-linked immunosorbent assay in the PBMCs of 29 patients with NTM lung disease and 15 healthy controls. Phytohemagglutinin (PHA)-induced IFN-γ production and lipopolysaccharide (LPS)-induced production of TNF-α and IL-12p40 were significantly lower in the PBMCs of patients with NTM lung disease than in those of the healthy controls. The production of these cytokines did not differ significantly between patients infected with Mycobacterium avium complex (MAC) and those infected with Mycobacterium abscessus; however, IL-10 production was lower in patients infected with M. abscessus than in those infected with MAC. Decreased IFN-γ, TNF-α, and IL-12 production may be associated with host susceptibility to the development of MAC and M. abscessus lung disease.     

Pulmonary infection with nontuberculous mycobacteria

Nontuberculous mycobacterial infections (NTM) are being increasingly recognized as a cause of chronic pulmonary disease. We recently reviewed the clinical, radiologic, and bacteriologic presentation of 89 adult patients ill enough to have been hospitalized between 1981 and 1985 with the diagnosis of NTM. Preexisting lung disease was present in 82% and alcohol abuse in 40%. Although M. avium complex was identified in 51% of the patients, M. xenopi, which is usually reported to occur infrequently, accounted for 38% of our cases and M. kansasii for only 9%. Treatment was limited by a high incidence of associated disease, in vitro drug resistance, drug toxicity, and a mortality rate of 32% within 18 months of admission. Nevertheless, bacteriologic conversion occurred in 29% of those treated. M. xenopi appears to be an important pathogen in southern Ontario. It differs from the other NTM by having a different pattern of in vitro drug resistance but not by its clinical or radiologic presentation.     

Identification and Characteristics of Co-isolation of Multiple Nontuberculous Mycobacteria

Objective Although multiple nontuberculous mycobacteria (NTM) species can be isolated from the same patient, little has been reported on co-isolation. We clarified the trends and characteristics of the co-isolation of multiple NTM species. Methods To collect data on multiple NTM isolation, we first extracted all patients who visited our hospital from 2006 through 2015 with a diagnosis of NTM lung diseases other than Mycobacterium avium complex (MAC) and then reviewed their medical records to evaluate the co-isolation of multiple NTM species. Results Of 213 patients with non-MAC lung disease, the most common NTM species was M. gordonae (32%), followed by M. kansasii (20%) and M. abscessus (14%). Non-MAC NTM lung disease tended to be associated with middle age with a low body mass index and male predominance. Multiple NTM species were isolated from 55 (26%) of the 213 patients. The clinical characteristics associated with multiple NTM species isolation included female predominance, never smokers and the absence of cavity lesions in the lungs. The highest co-isolation rate was observed in patients with M. gordonae isolation (30%), followed by M. furtuitum isolation (26%) and M. abscessus isolation (20%). Only MAC was isolated when co-isolated with M. abscessus. Among M. szulgai, M. peregrinum and M. terrae isolation, no other NTM species were detected. Conclusion Co-isolation of multiple NTM species was not uncommon, with 26% of patients with non-MAC NTM lung diseases showing co-isolation with multiple NTM species. Each NTM species had distinct characteristics in terms of co-isolation.     

Disseminated Mycobacterium kansasii infection with hepatic abscesses in a renal transplant recipient

P. Kaur, J.A. Fishman, J. Misdraji, M.C. Varma, C.N. Kotton. Disseminated Mycobacterium kansasii infection with hepatic abscesses in a renal transplant recipient
Transpl Infect Dis 2011: 13: 531–535. All rights reserved Abstract: Mycobacterium kansasii is the second most frequent cause of non‐tuberculous mycobacterial disease in the United States after Mycobacterium avium complex. While primarily it is a pulmonary disease, extrapulmonary manifestations are common. This case report describes a recent renal transplant recipient with disseminated M. kansasii infection presenting with hepatic abscesses, with discussion of clinical management issues and strategies, and a review of the literature.     

Epidemiology and clinical significance of mycobacterial respiratory infections in Central Greece

SETTING: A 750-bed tertiary referral hospital in Central Greece. OBJECTIVE: To determine the incidence of non-tuberculous mycobacteria (NTM) respiratory infection based on the isolation of NTM in respiratory specimens, to study their clinical significance and to evaluate the differences in clinical, radiological and demographic characteristics between patients with lung disease caused by NTM and that caused by Mycobacterium tuberculosis complex (MTC). DESIGN: A 3-year period prospective study to identify patients with positive NTM and MTC respiratory specimens. RESULTS: Between January 2004 and December 2006, 564 positive NTM cultures from 214 patients and 118 MTC cultures from the same number of patients were collected. The incidence rate of clinically significant NTM lung infection was 0.67, 0.54 and 0.94 cases per 100,000 population, and that of MTC infection of the lung was respectively 5.70, 5.28 and 5.10 cases/100,000 in the three study years. Smoking habits and chronic obstructive pulmonary disease were significant risk factors for NTM disease (P < 0.05 and P < 0.001, respectively). CONCLUSIONS: NTM incidence rates were lower than those reported in the rest of Europe and the USA. Further studies are needed to determine the prevalence and the significant geographic variability of NTM and their clinical significance at the national level.     

Health‐related quality of life,comorbidities and mortality in pulmonary nontuberculous mycobacterial infections: A systematic review

Nontuberculous mycobacterial (NTM) infections are increasing in disease frequency worldwide. This systematic review examines health‐related quality of life (HRQOL), comorbidities and mortality associated with pulmonary NTM disease. We searched MEDLINE, EMBASE, CINAHL, Scopus Life Sciences, conference proceedings and Google (earliest date available to February 2015) for primary studies. Eligible studies compared populations with and without pulmonary NTM disease in high‐income jurisdictions. We excluded studies on HIV/AIDS. All languages were accepted. Two reviewers followed MOOSE and PRISMA reporting guidelines and independently appraised quality using STROBE. All studies were summarized qualitatively regardless of quality. Of 3193 citations screened, we included 17 studies mostly from Taiwan (n = 5) and the USA (n = 4). Two studies assessed HRQOL; one assessed comorbidities, 11 assessed mortality, and three assessed multiple outcomes. Populations with pulmonary NTM reported significantly worse or similar HRQOL than the general population, depending on the instruments used. Some suggested greater prevalence of having bronchiectasis (n = 2) and greater risk of developing pulmonary tuberculosis (n = 1). Most (n = 7) suggested no difference in mortality, although only one was age‐matched and gender‐matched to the general population. Four suggested NTM populations had higher mortality—two of which compared with the general population and were deemed of high quality, while two compared with non‐NTM patients from hospital. High clinical heterogeneity in study design may explain discordant results. Bias assessments and controlling for confounding were carried out poorly. No consistent trends were observed although there is suggestion of an increased health burden from respiratory diseases and increased mortality associated with pulmonary NTM disease.