Efficacy of an oscillating positive expiratory pressure device in patients with Mycobacterium avium complex pulmonary disease.

Patients with Mycobacterium avium complex pulmonary disease (MAC-PD) often suffer from chronic symptoms such as sputum production, which reduces quality of life. Oscillatory positive expiratory pressure (OPEP) devices are used in physiotherapy to promote the clearance of respiratory secretions. We report two cases of improved lung function and improved scores on the Leicester Cough Questionnaire (LCQ) and the Breathlessness, Cough and Sputum Scale (BCSS) after the use of OPEP in patients with MAC-PD where treatment with guideline-based therapy, including amikacin liposome inhalation suspension, had proved ineffective for symptoms. Use of OPEP might maximize the efficacy of therapy and thereby improves outcomes in patients with MAC-PD. It is important to use both guideline-based therapy and OPEP, especially in patients whose health-related quality of life is affected by sputum symptoms. Further prospective studies are warranted to assess the benefit of adding OPEP to guidelines concerning therapy for patients with MAC-PD and sputum symptoms.

Exacerbating factors in elderly patients with Mycobacterium avium complex pulmonary disease.

No previous studies have examined Mycobacterium avium complex pulmonary disease (MAC-PD) in only elderly patients ⩾75 years old. Here, we investigated the exacerbating factors of MAC-PD in elderly patients and clarified cases that can be followed up without MAC medication. From April 2011 to March 2019, 126 advanced aged patients at our institute were newly diagnosed with MAC-PD, and could be observed based on radiological findings for over a year. Their medical records were retrospectively examined for clinical and radiological findings at the time of diagnosis and 1 year later. To identify the predictors of exacerbation, clinical characteristics of 109 treatment-naïve patients were compared between exacerbated and unchanged groups. Additionally, the unchanged group was followed for one more year. In the current study, positive acid-fast bacilli smears from the sputum test, the presence of cavitary lesions and extensive radiological findings, particularly abnormal shadows in ⩾3 lobes, were predictive of exacerbation among treatment-naïve elderly MAC-PD patients. In the unchanged group, <10% showed exacerbation of radiological findings within the subsequent year. In conclusion, if the sputum smear is negative, no cavitary lesions are present, and abnormal shadows are restricted to ⩽2 lobes, elderly patients with MAC-PD may remain untreated for a few years.

[Epidemiology, Clinical Presentation, Diagnosis and Treatment of Infections Caused by Mycobacterium chimaera]. / Epidemiologie, Klinik, Diagnostik und Therapie von Infektionen durch Mycobacterium chimaera.

The recognition, correct diagnosis and adequate clinical management of infections caused by atypical mycobacteria are challenging tasks in clinical practice. Invasive infections caused by Mycobacterium chimaera, a member of the Mycobacterium avium-intracellulare complex, have been increasingly reported over the past few years. Most infections occurred in patients who had undergone open-chest cardiothoracic surgery. Epidemiological and molecular studies showed that transmission of M. chimaera occurred through intraoperative aerosols derived from contaminated heater-cooler units, i. e. devices that are used to enable the extracardiac circuit in cardiothoracic surgery. Thus far, approximately 120 patient cases have been reported worldwide. The latency between exposure and onset of clinical symptoms may comprise several years. Clinical manifestations of M. chimaera infections include not only endocarditis and implant-associated infections, but also non-cardiac entities such as sarcoidosis-like symptoms, vertebral osteomyelitis and chorioretinitis. The pathogen can be detected in blood culture vials and in surgically obtained specimens from affected tissues, if specific microbiological tests for detection of mycobacteria are employed. There are no simple-to-use screening tests and a high clinical index of suspicion is thus mandatory in patients with previous exposure and compatible signs and symptoms. The successful treatment of M. chimaera infections requires the removal of infected devices and prolonged combination therapy with antimycobacterial drugs. This review summarises the clinical relevance, epidemiology, symptomatology, diagnosis and treatment of infections caused by M. chimaera, with a specific focus on pneumological aspects.

Resolution of a Localized Granuloma Caused by Mycobacterium avium-intracellulare Complex on the Cere of a Bruce's Green Pigeon (Treron waalia).

A 3-year-old female Bruce's green pigeon (Treron waalia) was presented with granulomatous inflammation of the cere and underlying tissues with osteomyelitis and bone proliferation of the dorsal premaxilla. Biopsy and culture revealed the presence of Mycobacterium avium-intracellulare complex, and multi-antimicrobial treatment was initiated with clarithromycin, ethambutol, rifabutin, and enrofloxacin. The cere lesion improved and no evidence of systemic granulomas was observed over 4 months of treatment, although leukocytosis and monocytosis persisted. Five months after discontinuation of antibiotic therapy, the white blood cell count had normalized, but distal beak irregularities and partial recurrence of the mass were present. The bird died 15 months after discontinuation of antibiotic therapy and necropsy revealed no evidence of active mycobacteriosis of the beak or cere. This report documents an unusual clinical presentation of mycobacteriosis, in addition to its successful resolution.

Disseminated Mycobacterium avium complex infection in a child with partial dominant interferon gamma receptor 1 deficiency in India.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by clinical disease caused by weakly virulent mycobacteria. All genes mutated in MSMD patients are involved in IFN-γ immunity. Autosomal partial dominant (PD) interferon-γ receptor 1 (IFN-γR1) deficiency is the most frequent abnormality affecting the group of MSMD patients leading to impaired response of IFN-γ. We describe here a patient from India with disseminated infection due to Mycobacterium avium intracellulare (MAC) including multifocal osteomyelitis and BCG disease. A heterozygous mutation in exon 6 of IFNGR1 gene was identified, conferring an autosomal PD IFN-γR1 deficiency. Patient had recurrence of mycobacterial disease during antibiotic therapy for which subcutaneous IFN-γ was added as a modality of treatment for resistant MAC infection.

Variable agreement among experts regarding Mycobacterium avium complex lung disease.

Data regarding many clinical aspects of pulmonary Mycobacterium avium complex (pMAC) are lacking. Guidelines rely substantially upon expert opinion, integrated through face-to-face meetings, variably weighting individual opinions. We surveyed North American non-tuberculous mycobacteria experts regarding clinical aspects of pMAC using Delphi methods. Nineteen of 26 invited experts (73%) responded, with extensive variability. Convergence could not be reached for most questions. Respondents described extensive uncertainty around specific issues. Findings underscore urgent need for more research.

Successful resumption of tocilizumab for rheumatoid arthritis after resection of a pulmonary Mycobacterium avium complex lesion: a case report.

BACKGROUND: Biological agents inhibiting TNF-α and other molecules involved in inflammatory cascade have been increasingly used to treat rheumatoid arthritis (RA). However, it remains controversial whether biological agents can be used safely in a patient with an underlying chronic infectious disease. CASE PRESENTATION: A 63-year-old woman who had been treated with tocilizumab (TCZ), anti-interleukin-6 receptor antibody, for RA presented to our outpatient clinic due to hemoptysis. She was diagnosed with pulmonary Mycobacterium avium complex (MAC) infection, and high-resolution computed tomography (HRCT) showed a single cavitary lesion in the right upper lobe. After diagnosis of pulmonary MAC disease, TCZ was discontinued and combination chemotherapy with clarithromycin, rifampicin, ethambutol and amikacin was started for MAC pulmonary disease. Since the lesion was limited in the right upper lobe as a single cavity formation, she underwent right upper lobectomy. As her RA symptoms were deteriorated around the operation, TCZ was resumed. After resumption of TCZ, her RA symptoms improved and a recurrence of pulmonary MAC infection has not been observed for more than 1 year. CONCLUSION: This case suggested that TCZ could be safely reintroduced after the resection of a pulmonary MAC lesion. Although the use of biological agents is generally contraindicated in patients with pulmonary MAC disease, especially in those with a fibrocavitary lesion, a multimodality intervention for MAC including both medical and surgical approaches may enable introduction or resumption of biological agents.

[Pulmonary mycobacterium intracellulare infection complicated with pneumothorax and chronic empyema].

A 75-year-old woman who had been treated for pulmonary Mycobacterium intracellulare infection was admitted to a nearby hospital because of hemoptysis, right pneumothorax, and empyema. She had been treated by thoracic drainage and pleural lavage, but was reffered to our hospital because of refractory empyema. Her chest radiograph and chest computed tomography( CT) showed right chronic empyema of which pleural aspirate was smear positive for acid-fast bacilli and positive for the polymerase chain reaction method(PCR)-Mycobacterium intracellulare. Serum levels of white blood cell and C-reactive protein(CRP) were found to be slightly elevated. She was treated with combined use of ethambutol, rifampicin, clarithromycin, and kanamycin and with pleural curettage by thoracoscopic surgery. After surgery additional treatment was done using urokinase which was administered into the thoracic cavity via an thoracic tube. Chronic empyema gradually improved with the treatment and the pleural effusion became bacterial free, enabling the patient to discharge from hospital without thoracic drainage.

Mycobacterium avium complex prosthetic joint infection: A systematic review of the literature and pooled analysis.

BACKGROUND: Mycobacterium avium complex (MAC) prosthetic joint infection (PJI) has been rarely reported. METHODS: This study aimed to investigate the epidemiology and outcomes of MAC PJI. A systematic review of the literature regarding the MAC infection following total joint arthroplasty including hip and knee joint was performed. Multiple databases were searched for published English-written articles up to May 2023. Studies that reported cases of PJI by MAC were reviewed. RESULTS: A total of 17 patients were identified and analyzed from 11 published studies. All patients presented with joint symptom of pain or swelling prior to the diagnosis and MAC was confirmed by culture. The most of the patients (16/17 patients, 94.1%) were noted to have underlying medical condition(s) that might have affected immunity. Treatment consisted of anti-MAC medication therapy only in two patients and anti-MAC medication therapy plus surgery in 15 patients. Among the patients who underwent surgery, 14 patients (82.3%) had removal of the prosthesis including seven patients who had two-stage surgery to have reimplantation of the prosthesis. No relapse of MAC infection was reported despite of one case of relapse of infection caused by different pyogenic bacteria. The rate of overall mortality was 29.4%, however, identified attributable mortality due to MAC infection was low (5.9%). CONCLUSION: PJI by MAC is a rare disease. However, MAC needs to be considered in the differential diagnosis in immunocompromised patients presenting with symptoms of PJI. Two-stage exchange arthroplasty may result in successful treatment outcomes without higher risks of relapse of infection if undertaken in association with appropriate active anti-MAC antibiotic therapy.

Therapy of refractory nontuberculous mycobacterial lung disease.

PURPOSE OF REVIEW: The prevalence of nontuberculous mycobacterial (NTM) lung disease is increasing in the USA. Clinicians are therefore encountering these patients with increasing frequency, with the attendant multiple therapeutic challenges presented by NTM lung disease including relatively frequent (compared with tuberculosis) treatment failure. RECENT FINDINGS: Critical elements for the successful treatment of Mycobacterium avium complex (MAC) lung disease include aggressive first therapeutic attempts and avoidance of the emergence of macrolide-resistant MAC strains, which are associated with worse treatment response and increased mortality. Reliably effective therapy for M. abscessus lung disease remains elusive but still usually requires parenteral agents. Lung resection surgery for selected patients is an important adjunct for both MAC and M. abscessus lung disease. Aside from surgery and parenteral antibiotics, there are very few data to support the efficacy of other drugs or interventions for patients who have failed the first-line therapy. SUMMARY: Clinicians who manage NTM lung disease will inevitably encounter patients who fail the first-line therapy. The choices for effective treatment of these patients are depressingly sparse. It is critically important to avoid creation of macrolide-resistant MAC strains and to carefully choose those NTM lung disease patients who will benefit from surgery.

[Diagnosis and treatment of pulmonary diseases caused by Mycobacterium avium complex].

Recently, the clinical importance of non-tuberculous mycobacteria(especially, Mycobacterium avium complex [MAC] respiratory infection) has been increasing. In addition, an official ATS/IDSA statement about diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases has been published in February, 2007. In this review article, clinical features and radiological findings of pulmonary MAC diseases mainly i) primarily fibrocavitary disease, and ii) nodular/bronchiectatic disease are described. Primarily fibrocavitary disease is characterized by cavitary lesions in upper lung fields in elderly subjects, smoking patients, or patients with pneumoconiosis. Nodular/bronchiectatic disease is characterized by centrilobular nodules and diffuse bronchiectases in the right middle lobe and the left lingula in middle-aged women. In addition, diagnosis and treatment for pulmonary diseases caused by MAC are also described.

Aortic Graft Infection With Mycobacterium Avium Complex.

Aortic graft infections are uncommon complications after endovascular aortic surgery. In the majority of cases, gram-positive and then gram-negative organisms are the causative agents leading to this condition. Atypical organisms are traditionally not responsible for graft infection unless the patient is immunocompromised. We are reporting a case of culture-confirmed mycobacterium avium complex infection of an aortic graft in a well-controlled patient with HIV who had an undetected viral load and a CD4 count of 324 while on highly active antiretroviral therapy.

Distribution and outcomes of infection of Mycobacterium avium complex species in cystic fibrosis.

BACKGROUND: The majority of nontuberculous mycobacterial (NTM) pulmonary infections in people with cystic fibrosis (CF) are caused by Mycobacterium avium complex (MAC) species. Data on MAC species distribution and outcomes of infection in CF are lacking. METHODS: This was a single center, retrospective study. MAC isolates had species identification with MLSA of rpoB and the 16S23S ITS region. Clinical data were compared between species. RESULTS: Twenty-three people with CF and 57 MAC isolates were included. Infection with M. avium was the most common (65.2%). M. intracellulare was associated with higher rates of NTM disease, younger age, and steeper decline in lung function prior to infection. CONCLUSIONS: We observed worse clinical outcomes in people with M. intracellulare infection relative to other MAC species. Further investigation of clinical outcomes of MAC infection among CF patients is warranted to better define the utility of species-level identification of MAC isolates in CF.

When and how to treat pulmonary non-tuberculous mycobacterial diseases.

Non-tuberculous mycobacteria are ubiquitous environmental organisms that have been recognized as a cause of pulmonary infection for over 50 years. Traditionally patients have had underlying risk factors for development of disease; however, the proportion of apparently immunocompetent patients involved appears to be rising. Not all patients culture-positive for mycobacteria will have progressive disease, making the diagnosis difficult, though criteria to aid in this process are available. The two main forms of disease are cavitary disease (usually involving the upper lobes) and fibronodular bronchiectasis (predominantly middle and lingular lobes). For patients with disease, combination antibiotic therapy for 12-24 months is generally required for successful treatment, and this may be accompanied by drug intolerances and side-effects. Published success rates range from 30% to 82%. As the progression of disease is variable, for some patients, attention to pulmonary hygiene and underlying diseases without immediate antimycobacterial therapy may be more appropriate. Surgery can be a useful adjunct, though is associated with risks. Randomized controlled trials in well-described patients would provide stronger evidence-based data to guide therapy of non-tuberculous mycobacteria lung diseases, and thus are much needed.

Vacuum sealing drainage: A novel treatment method for primary cutaneous Mycobacterium intracellulare infection.

The incidence of primary cutaneous Mycobacterium intracellulare infection is very low. We report a case of primary cutaneous M. intracellulare infection which presented as painful erythematous swelling of the right upper limb without systemic involvement. A novel technique of vacuum sealing drainage was successfully implemented after antimycobacterial treatment proved ineffective at the end of 3 months. Our technique also revealed some additional practical advantages.

Mycobacteria-Specific T Cells May Be Expanded From Healthy Donors and Are Near Absent in Primary Immunodeficiency Disorders.

Mycobacterial Infections can be severe in patients with T-cell deficiency or phagocyte disorders, and treatment is frequently complicated by antimicrobial resistance. Restoration of T-cell immunity via stem cell transplantation facilitates control of mycobacterial infections, but presence of active infections during transplantation is associated with a higher risk of mortality. Adoptive T cell immunotherapy has been successful in targeting viruses, but has not been attempted to treat mycobacterial infections. We sought to expand and characterize mycobacterial-specific T-cells derived from healthy donors in order to determine suitability for adoptive immunotherapy. Mycobacteria-specific T-cells (MSTs) were generated from 10 healthy donors using a rapid ex vivo expansion protocol targeting five known mycobacterial target proteins (AG85B, PPE68, ESXA, ESXB, and ADK). MSTs were compared to T-cells expanded from the same donors using lysate from M. tuberculosis or purified protein derivative from M. avium (sensitin). MST expansion from seven patients with primary immunodeficiency disorders (PID) and two patients with IFN-γ autoantibodies and invasive M. avium infections. MSTs expanded from healthy donors recognized a median of 3 of 5 antigens, with production of IFN-γ, TNF, and GM-CSF in CD4+ T cells. Comparison of donors who received BCG vaccine (n = 6) to those who did not (n = 4) showed differential responses to PPE68 (p = 0.028) and ADK (p = 0.015) by IFN-γ ELISpot. MSTs expanded from lysate or sensitin also recognized multiple mycobacterial antigens, with a statistically significant differences noted only in the response to PPE68 (p = 0.016). MSTs expanded from patients with primary immunodeficiency (PID) and invasive mycobacterial infections showed activity against mycobacterial antigens in only two of seven subjects, whereas both patients with IFN-γ autoantibodies recognized mycobacterial antigens. Thus, MSTs can be generated from donors using a rapid expansion protocol regardless of history of BCG immunization. Most tested PID patients had no detectable T-cell immunity to mycobacteria despite history of infection. MSTs may have clinical utility for adoptive immunotherapy in T-cell deficient patients with invasive mycobacterial infections.