Effect of comorbidities on mortality in patients with nontuberculous mycobacterial infection in Korea: National Health Insurance Service-National Sample Cohort data.

Patients with nontuberculous mycobacteria (NTM) infection have multiple comorbidities, but the impact of comorbidities on mortality are not well known. We aimed to compare the mortality between people with and without NTM infection and associated comorbidities and their prognostic value on mortality using National Health Insurance Service-National Sample Cohort data from 2006 to 2019. In this matched cohort study, people with and without NTM infection aged 20-89 years were matched 1:4 by sex, age, region, and income. The hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality in patients with NTM infection were estimated using a Cox proportional hazard regression model. In total, 2421 patients with NTM infection (mean age, 54.8 years) and 9684 controls were included. NTM-infected patients had a significantly increased risk of mortality than matched controls in the multivariable model adjusted for age, sex, region, income, and Charlson comorbidity index (aHR = 1.88, 95% CI 1.65-2.14). Among patients with NTM infection, respiratory comorbidities including chronic obstructive pulmonary disease, asthma, interstitial lung disease, and moderate to severe liver disease and malignancy were positively associated with mortality. NTM infection was independently associated with an increased risk of mortality, and mortality risk in patients with NTM infection may be increased by coexisting comorbidities.

Pulmonary Mycobacterium avium Complex With Adenocarcinoma of the Lung: A Case Report.

Nontuberculous mycobacteria are responsible for causing pulmonary as well as extrapulmonary diseases. These organisms are often multidrug resistant and management of these cases poses a therapeutic challenge. Lung cancer has been a prevalent challenge globally with a high mortality rate in affected individuals. Adenocarcinoma poses debilitating outcomes in most patients by inflicting a diagnostic and therapeutic challenge. The concomitant association of adenocarcinoma and Mycobacterium avium complex worsens the prognosis causing a challenge in managing such cases. We present a rare association between adenocarcinoma and pulmonary Mycobacterium avium complex complicating the traditional therapeutic regime. A different approach in the administration of therapy for this unique concomitant association between two debilitating diseases is outlined in the presented report.

Nontuberculous mycobacterial pulmonary disease presenting as bronchiolitis pattern on CT without cavity or bronchiectasis.

BACKGROUND: This study aimed to investigate the radiological changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) having bronchiolitis patterns on computed tomography (CT). METHODS: We retrospectively reviewed the final diagnosis and radiologic changes of patients suspected of having NTM-PD without cavity or bronchiectasis on CT image, between January 1, 2005 and March 31, 2021. NTM-PD was diagnosed based on the American Thoracic Society and Infectious Diseases Society of America criteria. The initial and final CT findings (bronchiectasis, cellular bronchiolitis, cavity formation, nodules, and consolidation) were compared between patients diagnosed with and without NTM-PD. RESULTS: This study included 96 patients and 515 CT images. The median CT follow-up duration was 1510.5 (interquartile range: 862.2-3005) days. NTM-PD was recognized in 43 patients. The clinical variables were not significantly different between patients with and without NTM-PD, except for underlying chronic airway disease (P < 0.001). Nodule and consolidation were more frequently observed on the initial CT scans of patients with NTM-PD compared with those without (P < 0.05). On the final follow-up CT scan, bronchiectasis (P < 0.001), cavity (P < 0.05), nodule (P < 0.05), and consolidation (P < 0.05) were more frequently observed in patients with NTM-PD. Among the 43 patients with NTM-PD, 30 showed a radiological progression on CT, with bronchiectasis (n = 22) being the most common finding. The incidence of bronchiectasis increased over time. CONCLUSION: The bronchiolitis pattern on CT images of patients with NTM-PD showed frequent radiological progression during the follow-up period.

Clinical Characteristics and Outcomes of Extrapulmonary Nontuberculous Mycobacterial Infections in a Tertiary-Care Hospital: A Retrospective Study.

Background/Objectives: The incidence of nontuberculous mycobacterial (NTM) infections has increased globally; however, the clinical manifestations and optimal treatment strategies for extrapulmonary NTM infections remain poorly defined. This study assessed the clinical manifestations and treatment outcomes of extrapulmonary NTM infections. Methods: Data from adult patients with suspected extrapulmonary NTM infections at a tertiary-care hospital from 2009-2022 were categorized into NTM disease and isolation groups. Diagnosis of NTM disease relied on stringent criteria, whereas isolation required NTM isolation without meeting the criteria for infection. Results: Among 75 patients evaluated, 32 (42%) were diagnosed with NTM disease and 43 (57%) with NTM isolation. History of immunosuppressant use within the past 3 months (p = 0.070) and injection (p = 0.001) were more frequent in the disease group. The median interval from symptom onset to evaluation was 106.6 and 20 days in the disease and isolation groups, respectively. The prevalence of positive NTM polymerase chain reaction results (36.4%, p = 0.003) and acid-fast bacillus staining (39.1%, p < 0.001) was significantly higher in the disease group than in the isolation group. Mycobacterium intracellulare (21.9%), M. abscessus (15.6%), M. chelonae (9.4%), and M. fortuitum complex (9.4%) were the most frequently identified species. Of the 27 patients in the disease group who received treatment, 13 improved, four experienced treatment failure, seven were lost to follow-up, and three died during treatment, with one death directly attributable to NTM disease. Conclusions: NTM disease exhibits a spectrum of clinical manifestations. Accurate diagnosis is crucial for initiating effective treatment.

Tuberculosis and Nontuberculous Mycobacterial Infections in Patients with Spondyloarthritis: A Population-Based Study.

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Subcutaneous infection caused by Mycobacterium abscessus following botulinum toxin injections: A case report and literature review.

BACKGROUND: The rapid development of cosmetic injections has led to an increased incidence of nontuberculous mycobacterial (NTM) infection. PATIENTS AND METHODS: Here, we presented a case of cutaneous Mycobacterium abscessus infection subsequent to botulinum toxin injection for treating masseter hypertrophy, and reviewed the literature on skin and soft tissue infections caused by NTM after cosmetic injections. RESULTS AND CONCLUSIONS: The patient underwent surgical excision and regular antibiotic therapy and has had nearly 2 months of follow-up without any signs of infection. The diagnosis and treatment of NTM infection have always been challenging, and further research is needed to standardize and guide the treatment.

Tolerability Outcomes of American Thoracic Society/Infectious Diseases Society of America Guideline-Recommended Multidrug Antibiotic Treatment for Mycobacterium avium Complex Pulmonary Disease in US Medicare Beneficiaries With Bronchiectasis.

BACKGROUND: Nontuberculous mycobacteria are environmental organisms that are increasingly causing chronic and debilitating pulmonary infections, of which Mycobacterium avium complex (MAC) is the most common pathogen. MAC pulmonary disease (MAC-PD) is often difficult to treat, often requiring long-term multidrug antibiotic therapy. RESEARCH QUESTION: Is there an association between various guideline-based three-drug therapy (GBT) regimens and (1) therapy-associated adverse events or (2) regimen change/discontinuation, within 12 months of therapy initiation? STUDY DESIGN AND METHODS: In a retrospective cohort study, we examined tolerability outcomes of GBT regimens for MAC-PD in 4,626 US Medicare beneficiaries with bronchiectasis, who were prescribed a GBT as initial antibiotic treatment for presumed MAC-PD during 2006 to 2014. Using multivariable Cox proportional hazard regression, we estimated adjusted hazard ratios (aHRs) to compare the risk of adverse events and regimen change/discontinuations within 12 months of therapy initiation in various GBT regimens. RESULTS: The cohort had a mean age ± SD of 77.9 ± 6.1 years at treatment start, were mostly female (77.7%), and were mostly non-Hispanic White (87.2%). The risk of regimen change/discontinuation within 12 months of therapy was higher for clarithromycin-based regimens than azithromycin-based regimens (aHR, 1.12; 95% CI, 1.04-1.20 with rifampin; aHR, 1.11; 95% CI, 0.93-1.32 with rifabutin as the companion rifamycin), and for rifabutin-containing regimens than rifampin-containing regimens (aHR, 1.49; 95% CI, 1.33-1.68 with azithromycin; aHR, 1.47; 95% CI, 1.27-1.70 with clarithromycin as the companion macrolide). The aHR comparing regimen change/discontinuation with clarithromycin-ethambutol-rifabutin and azithromycin-ethambutol-rifampin was 1.64 (95% CI, 1.43-1.64). INTERPRETATION: Overall, an azithromycin-based regimen was less likely to be changed or discontinued than a clarithromycin-based regimen, and a rifampin-containing regimen was less likely to be changed or discontinued than a rifabutin-containing regimen within 12 months of therapy start. Our work provides a population-based assessment on the tolerability of multidrug antibiotic regimens used for the treatment of MAC-PD.

CXCL9 as a Reliable Biomarker for Discriminating Anti-IFN-γ-Autoantibody-Associated Lymphadenopathy that Mimics Lymphoma.

The diagnosis of adult-onset immunodeficiency syndrome associated with neutralizing anti-interferon γ autoantibodies (AIGA) presents substantial challenges to clinicians and pathologists due to its nonspecific clinical presentation, absence of routine laboratory tests, and resemblance to certain lymphoma types, notably nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI). Some patients undergo lymphadenectomy for histopathological examination to rule out lymphoma, even in the absence of a preceding clinical suspicion of AIGA. This study aimed to identify reliable methods to prevent misdiagnosis of AIGA in this scenario through a retrospective case-control analysis of clinical and pathological data, along with immune gene transcriptomes using the NanoString nCounter platform, to compare AIGA and nTFHL-AI. The investigation revealed a downregulation of the C-X-C motif chemokine ligand 9 (CXCL9) gene in AIGA, prompting an exploration of its diagnostic utility. Immunohistochemistry (IHC) targeting CXCL9 was performed on lymph node specimens to assess its potential as a diagnostic biomarker. The findings exhibited a significantly lower density of CXCL9-positive cells in AIGA compared to nTFHL-AI, displaying a high diagnostic accuracy of 92.3% sensitivity and 100% specificity. Furthermore, CXCL9 IHC demonstrated its ability to differentiate AIGA from various lymphomas sharing similar characteristics. In conclusion, CXCL9 IHC emerges as a robust biomarker for differentiating AIGA from nTFHL-AI and other similar conditions. This reliable diagnostic approach holds the potential to avert misdiagnosis of AIGA as lymphoma, providing timely and accurate diagnosis.

Pulmonary Mycobacterium abscessus Infection: A Pathogen in Disguise.

The incidence of infections caused by nontuberculous mycobacteria (NTM) is rising around the world, and they are becoming increasingly difficult to treat due to the bacteria being drug-resistant to several antibiotics commonly used in practice. Mycobacterium abscessus complex (MABC) is particularly difficult to treat as it is one of the most antibiotic-resistant species and, therefore, has limited treatment options that are effective at clearing the infection. We present the case of an 81-year-old female who was diagnosed with Mycobacterium abscessus after several hospital admissions in a short period of time for similar complaints, and we will discuss her diagnosis and possible treatment plan. This case explores the challenges that physicians face in diagnosing NTM infections due to them mimicking several other conditions and raises the importance of having a high clinical suspicion.

Nontuberculous Mycobacterial Infection Mimicking Lung Cancer in A Patient with Usual Interstitial Pneumonia Pattern Interstitial Lung Disease: A Case Report.

BACKGROUND: It has been reported that structure damage in the parenchymal lung disease such as idiopathic pulmonary fibrosis (IPF) is associated with high susceptibility to nontuberculous mycobacterial (NTM) infection. Radiologic features of NTM lung disease in destructive lung parenchyma can be atypical, which can cause confusion with other diseases including malignancy. Prompt and accurate identification of newly developed lesions in the follow-up computed tomography (CT) of IPF patients is challenging but crucial. CASE REPORT: We reported a case of an NTM infection in a patient with IPF, manifested as a mass-like consolidation with cavitation on chest CT, mimicking lung cancer. CONCLUSION: Being aware of the unusual radiologic features of NTM lung disease in IPF patients can be useful in the differential diagnosis of newly detected lesions.

Nontuberculous mycobacterial infection following cat scratch in the setting of topical steroid use.

Infections due to nontuberculous mycobacteria (NTM) are caused by mycobacterial species other than Mycobacterium tuberculosis, M. leprae, and M. bovis. Patients who are immunocompromised have increased susceptibility to pulmonary, lymphatic, and skin infections by these pathogens. We present a case of a 78-year-old male who presented to dermatology with a left dorsolateral hand infection after sustaining cat scratches in the setting of topical steroid therapy for suspected pyoderma gangrenosum. A shave biopsy of the lesion showed granulomatous dermatitis and associated acid-fast bacilli, while tissue culture grew Mycobacterium chelonae. This case demonstrates cat scratches as an uncommon risk factor for cutaneous NTM disease. Although an association between cat scratches and human NTM infections has only been reported in two previous cases, it must be considered in cases of unusual and persistent cutaneous lesions, especially in immunocompromised patients, even those with only local immunosuppression from topical agents.

A case of mediastinal abscess and infected aortic aneurysm caused by dissemination of Mycobacterium abscessus subsp. massiliense pulmonary disease.

An 81-year-old man was admitted to our hospital because of fever and malaise that had persisted for 3 months. The patient had undergone two aortic valve replacements, 10 and 5 years previously, because of aortic valve regurgitation and infectious endocarditis. He also had had asymptomatic Mycobacterium abscessus complex (MABC) pulmonary disease for the two previous years. Contrast-enhanced computed tomography showed a mediastinal abscess and an ascending aortic aneurysm. Mycobacterium abscessus subsp. massiliense was cultured from his blood, suggesting the aortic aneurysm was secondary to infection of an implanted device. After enlargement over only a few days, a leakage of contrast medium to the mediastinal abscess was found on computed tomography. The patient was diagnosed with rupture of an infectious aortic aneurysm, and emergency aortic replacement and drainage of the mediastinal abscess were successful. The patient was treated with several antibiotics, including meropenem, amikacin, and clarithromycin, and his general condition improved. Cultures from both the mediastinal abscess and a pericardial patch that was placed at the time of surgery 5 years previously revealed MABC. In our case, the infected aortic aneurysm most likely resulted from MABC pulmonary disease rather than from previous intraoperative contamination. This route of infection is rare. Physicians should be aware of the possibility of dissemination and subsequent infection of implants related to MABC pulmonary disease.

Treatment of Nontuberculous Mycobacterial (NTM) Pulmonary Infection in the US Bronchiectasis and NTM Registry: Treatment Patterns, Adverse Events, and Adherence to American Thoracic Society/Infectious Disease Society of America Treatment Guidelines.

Among 1038 participants with pulmonary Mycobacterium avium complex and 120 with Mycobacterium abscessus enrolled in the US Bronchiectasis and NTM Research Registry, less than half received antibiotic therapy in the 24 months before registry enrollment, of which less than half were guideline based. Adverse effects occurred in 21% of therapy recipients, of whom 33% discontinued therapy.

A successful salvage story: Uveitis with nontuberculous mycobacterial infection in a patient on secukinumab.

The reported occurrence of ocular infections with nontuberculous mycobacterial (NTM) infections has been increasing in the past few decades. NTM are known to cause intraocular infections as well as infections of the ocular appendages and are often recalcitrant to medical therapy. Uveal involvement due to NTM is rare and most reported cases have predisposing factors such as cataract surgery or immunocompromised states. Diagnosis and treatment pose challenge due to difficulty in procuring sufficient clinical material to obtain microbial diagnosis and inadequate response to medical therapy. The clinical challenge is further heightened in the presence of an underlying rheumatologic disease that is known to cause uveitis. We share the case of a young gentleman with ankylosing spondylitis who was being treated with secukinumab with good response to joint symptoms. He developed sudden onset uveitis which was diagnosed to be due to NTM infection based on aqueous humor polymerase chain reaction studies. He had a good clinical response to an empirical anti-mycobacterial regime with the restoration of vision. This report narrates the first case of NTM uveitis secondary to secukinumab therapy.

Development of Rheumatoid Arthritis in Cavitary Mycobacterium avium Pulmonary Disease: A Case Report of Successful Treatment with CTLA4-Ig (Abatacept).

BACKGROUND: Nontuberculous mycobacterial pulmonary disease (NTM-PD) often develops in patients with rheumatoid arthritis (RA), especially during immunosuppressive treatment, including biological disease-modifying antirheumatic drugs. NTM-PD is associated with airway lesions such as bronchiectasis, which is frequently seen in RA patients. Distinguishing which diseases cause the pulmonary lesion is difficult. However, there are limited reports of the development of RA during the follow-up of NTM-PD and how biological agents should be administered in these conditions, especially with cavitary lesions. CASE PRESENTATION: A 62-year-old woman with hemosputum was referred to our hospital, where she was diagnosed with Mycobacterium avium pulmonary disease. She began treatment with several antibiotics, including clarithromycin, ethambutol, rifampicin, and amikacin. In the course of treatment, M. avium became macrolide-resistant. Five years after beginning antibiotic treatment, she felt arthralgia in the fingers and wrists and had a high titer of rheumatoid factor and anticitrullinated peptide antibody, with which we diagnosed RA. Methotrexate, prednisolone, and iguratimod were subsequently administered, but the activity of RA gradually worsened. Meanwhile, M. avium changed to a macrolide-susceptible strain, her sputum smear results remained almost negative, and the NTM-PD disease was well controlled with antimicrobial therapy, despite her having cavitary lesions. Therefore, we started using CTLA4-Ig (abatacept). RA symptoms were substantially ameliorated. The pulmonary lesions and NTM-PD worsened mildly, but her pulmonary symptoms were stable. CONCLUSION: Physicians should be mindful of the etiologies of bronchiectasis, including RA, even in patients with a long-term history of treatment for bronchiectasis and NTM-PD. When NTM-PD is well controlled, even with remaining cavitary lesions, abatacept may be an option for patients with RA based on a comprehensive assessment of disease progression using NTM sputum smear/culture, computed tomography findings, and treatment response.

Anti-interferon-γ Antibody-seropositive Disseminated Nontuberculous Mycobacterial Infection Mimicking POEMS and TAFRO Syndromes.

Disseminated nontuberculous mycobacterial infection (DNTM) is typically observed in immunocompromised hosts. Recently, it has been reported that healthy individuals with serum neutralizing autoantibodies for interferon (IFN)-γ can also develop DNTM. We herein report a case of anti-IFN-γ antibody-seropositive DNTM caused by Mycobacterium kansasii with symptoms mimicking TAFRO or POEMS syndrome, including anasarca, organomegaly, skin pigmentation, polyneuropathy, osteosclerotic change, thrombocytopenia, serum M protein, high C-reactive protein level, and reticulin fibrosis. The combination of antimicrobial chemotherapy with glucocorticoid and intravenous immunoglobulin improved his symptoms. Glucocorticoids may be an effective method of suppressing the production of anti-IFN-γ antibodies in DNTM.

Immunotactoid Glomerulopathy with Nontuberculous Mycobacterial Infection: A Novel Association.

A 70-year-old woman underwent a renal biopsy due to nephrotic syndrome. She had suffered from nontuberculous mycobacterial infection (NTM) for 14 years. The patient was diagnosed as having membranoproliferative glomerulonephritis (MPGN) type 3 and immunoglobulin (Ig)-associated MPGN based upon LM/erythromycin and IF findings, respectively. In high-magnification imaging, electron-dense deposits showed immunotactoid glomerulopathy (ITG). There was no evidence of hematological cancer, and the patient improved after receiving treatments for NTM. To the best of our knowledge, this patient is the first to show an association between ITG and NTM. Although ITG is generally considered as related to lymphoproliferative disease, it is suggested that ITG is driven by bacterial infection and is a potential outcome of Ig-associated MPGN.

Validity of Diagnosis Code-Based Claims to Identify Pulmonary NTM Disease in Bronchiectasis Patients.

Nontuberculous mycobacteria infection is increasing in incidence and can lead to chronic, debilitating pulmonary disease. We investigated the accuracy of diagnosis code-based nontuberculous mycobacteria lung disease claims among Medicare beneficiaries in the United States. We observed that these claims have moderate validity, but given their low sensitivity, incidence might be underestimated.

Incidence of ocular inflammation among patients with active tuberculosis or nontuberculous mycobacterial infections in a tertiary hospital in Japan.

PURPOSE: This study aimed to elucidate the incidence of ocular involvement among patients with active tuberculosis (TB) or nontuberculous mycobacterial (NTM) infection in a hospital in Japan. METHODS: Patients with active TB or NTM infection at Yoshijima Hospital from April 2017 to July 2018 were included in this retrospective study. All patients underwent ophthalmic examinations, including fundus evaluation under pupil dilation, before initiation of antibiotic therapy. Patients with ocular inflammation were regularly followed up by ophthalmologists. RESULTS: In total, 101 patients with active TB and 27 patients with active NTM infection underwent ophthalmic examinations during the study period. Seven patients with TB (6.9%) had ocular inflammation; four had bilateral involvement. In these seven patients, ocular inflammation comprised anterior uveitis (n = 2), intermediate uveitis (n = 1), posterior uveitis (n = 4). Choroidal tubercles were observed in two patients with posterior uveitis. Female sex was associated with higher incidence of ocular inflammation among patients with TB. Conversely, no patients with NTM infection had ocular inflammation. CONCLUSION: Ocular inflammation was present in approximately 7% of patients with active TB. Although TB choroiditis is presumed to be rare in Japan, approximately 30% of the patients with ocular inflammation exhibited choroidal lesions in this study. In contrast, no ocular inflammation was observed among patients with systemic NTM infection.

Nontuberculous mycobacterial infections in children in the Czech Republic in the period 2003-2018.

AIM: Comparision of the incidence of cervical lymphadenitis caused by nontuberculous mycobacteria in two equal time periods before and after the ending of widespread calmetization (tuberculosis vaccination). Backgroung. From 2011 to 2018, 89 children were registered in the Tuberculosis Register with cervical lymphadenitis caused by nontuberculous mycobacteria, as confirmed by cultivation. In the majority of cases, the infection was caused by a mycobacterium belonging to the Mycobacterium avium complex. Only 7 cases of cervical lymphadenitis of the same etiology were registered during the same time interval between 2003 and 2010. The authors consider the ending of widespread calmetization (tuberculosis vaccination) in 2010 to be the main cause of the growing incidence. METHOD: A comparison of data for the period 2003-2018 about cases of the illness caused by atypical mycobacteria as reported in the Tuberculosis Register. RESULTS: The average incidence per year in the first interval was 0.04/100 000 children and in the second interval 0.53/100 000 children. During the second time interval, there was an increase from 0.14/100 000 children in 2011 to 1.40/100 000 children in 2018. While the incidence during the first time interval did not show any time trend (P=0.885), the year 2010 marks a significant turning point, with growth during the second interval being highly statistically significant (P<0.001).