Disseminated Mycobacterium avium Infection with Different Clinical Presentation in Two Human Immunodeficiency Virus-positive Patients.

ABSTRACT: Microorganisms belonging to the Mycobacterium avium complex (MAC) are ubiquitous in the environment, but only a minority of infected persons develop disease. An underlying lung disease or immune deficiency is a prerequisite for clinical manifestation. However, disseminated MAC disease primarily manifests in people living with human immunodeficiency virus (HIV) in the severe immunodeficiency stage with a whole host of clinical symptoms. We present two cases of disseminated M. avium infection in people living with HIV in the stage of severe immunodeficiency. Both patients exhibited distinct disease progression, with the absence of pulmonary symptoms being a common characteristic. The first patient predominantly experienced high fever, accompanied by diarrhea and severe anemia. The normothermia in the second patient was incongruent with the presence of marked cachexia, severe abdominal pain, and magnetic resonance imaging evidence of abdominal lymph node involvement. The causative agent was isolated from both sputum and stools. The patients underwent treatment that comprised aminoglycoside, macrolide, ethambutol, and rifampicin. Although both patients achieved optimal viral suppression of HIV, the immunologic response to antiretroviral therapy was suboptimal. The first patient died in the setting of severe immunodeficiency due to the development of decompensated liver cirrhosis, while the second patient demonstrated a slight reverse course of the disease.

Non-vertebral Mycobacterium avium complex osteomyelitis in an immunocompetent patient.

Mycobacterium avium complex (MAC) is a ubiquitous soil pathogen that is an uncommon cause of diseases in immunocompetent patients. In this case, we describe the presentation of an otherwise healthy man in his 50s presenting with months of malaise and severe hip pain, with aspiration initially yielding no bacteria and presumed fastidious infection. He was treated with irrigation and debridement, surgical stabilisation of the femoral neck and conventional broad-spectrum antibiotics with final cultures diagnostic of MAC osteomyelitis. This case serves to demonstrate the importance of clinical suspicion and appropriate workup of this unusual case of MAC hip osteomyelitis in an otherwise immunocompetent patient.

Pulmonary nocardiosis following nodular bronchiectatic Mycobacterium avium complex pulmonary disease in an immunocompetent patient.

A woman in her 70s with a history of nodular bronchiectatic Mycobacterium avium complex pulmonary disease (MAC-PD) presented with an exacerbated productive cough and worsening findings on chest imaging. Although repeated sputum culture tests were negative for acid-fast bacilli and only revealed normal respiratory flora, a bronchoscopy identified Nocardia sp. Consequently, she was diagnosed with pulmonary nocardiosis and was successfully treated with levofloxacin. It is known that pulmonary nocardiosis can manifest in immunocompetent individuals with bronchiectasis. For cases of refractory nodular bronchiectatic MAC-PD, it is vital to consider bronchoscopy to identify potential co-infections, such as Nocardia.

Simultaneous diagnosis of allergic bronchopulmonary aspergillosis and Mycobacterium avium complex lung disease.

Allergic bronchopulmonary aspergillosis (ABPA) and Mycobacterium avium complex lung disease (MAC-LD) often coexist because bronchiectasis, caused by ABPA or MAC, might be an important predisposing factor for both conditions. Here, we describe a man with asthma symptoms who had centrilobular small nodules and mucoid impaction on chest CT. We diagnosed the patient with simultaneous ABPA and MAC-LD on the basis of bronchoscopy findings. Itraconazole monotherapy led to substantial clinical improvement, avoiding the adverse effects of systemic corticosteroids. Sputum culture conversion of MAC was achieved after switching from itraconazole monotherapy to combination therapy comprising clarithromycin, rifampicin and ethambutol. ABPA recurred but was controlled by reinitiation of itraconazole. Overall, corticosteroid management was avoided for 38 months. Itraconazole monotherapy may be selected as initial treatment for ABPA with chronic infection, including MAC.

Multiple bacterial culture positivity reflects the severity and prognosis as bronchiectasis in Mycobacterium avium complex pulmonary disease.

BACKGROUND: Bacterial coinfections are observed in 19-66% of patients with Mycobacterium avium complex pulmonary disease (MAC-PD) during the entire duration of the disease. The impact of bacterial coinfection at diagnosis on the clinical course of MAC-PD has not been reported. METHODS: Among 558 patients diagnosed with MAC-PD between January 2016 and December 2020, 218 patients who underwent sputum culture tests twice or more within one year before and after diagnosis were included. We compared the patient characteristics and disease courses between the patients who had the same bacterial species detected twice or more (bacterial culture positive group: BCP group) and those who never had bacteria cultured (bacterial culture negative group: BCN group). RESULTS: We included 70 patients in the BCP group and 74 in the BCN group. The radiological findings showed that BCP at diagnosis correlated with a high modified Reiff score. During the median follow-up period of 42 months, the patients in the BCP group were more likely to accomplish spontaneous sputum conversion of MAC. The treatment initiation rate for MAC-PD in the BCP group was lower than that in the BCN group (41.4% vs. 67.6%, P = 0.003). In contrast, the time to the first bronchiectasis exacerbation in the BCP group was shorter than that in the BCN group, and the frequency of bronchiectasis exacerbations was higher in the BCP group. CONCLUSIONS: Patients with BCP at diagnosis are less likely to initiate treatment for MAC-PD and more likely to develop bronchiectasis exacerbation.

Unravelling the mystery of a rare infection: a challenging case of pulmonary sequestration with Mycobacterium avium complex and the importance of a thorough microbiological investigation.

Pulmonary sequestration is a rare congenital condition. It is a dysplastic lung tissue with a separate systemic blood supply and without a bronchial tree connection. The emergence of a superimposed infection can lead to its diagnosis, such as Staphylococcus aureus, Pseudomonas aeruginosa, Nocardia asteroids and Aspergillus sp pneumonia. Mycobacterium avium complex (MAC) superimposed disease is exceedingly rare. We report a case of a man in his third decade without known medical disorders presenting with a persistent cough. After an extensive microbiological workup, an MAC infection was diagnosed. An elevated carbohydrate antigen 19-9 (CA 19-9) was also noted. He was treated with antimycobacterial therapy and lobectomy resulting in clinical improvement and CA19-9 normalisation. This case illustrates the value of comprehensive microbiological investigations in patients with chronic respiratory symptoms and imaging findings that are not typical of bacterial pneumonia. Clinical studies remain needed to investigate the utility of CA 19-9 in a scoring system to guide MAC therapy.

Case Report: Missing zinc finger domains: hemophagocytic lymphohistiocytosis in a GATA2 deficiency patient triggered by non-tuberculous mycobacteriosis.

Haploinsufficiency of GATA2, also known as GATA2 deficiency, leads to a wide spectrum of clinical manifestations. Here we described another 28-year-old man with a GATA2 variant who also suffered from hemophagocytic lymphohistiocytosis(HLH), who was finally diagnosed with HLH triggered by Mycobacterium avium bloodstream infection due to primary immunodeficiency. We reviewed GATA2 deficiency patients with HLH and found that GATA2 variants causing loss of zinc finger domains were associated with HLH, and erythema nodosa might be an accompanying symptom.

Mycobacterial infection after COVID-19 pneumonia / Infección por micobacterias tras neumonía por COVID-19

A 69-year-old man with a history of hypertrophic cardiomyopathy and major depressive disorder was admitted to the Emergency Department with fever, weakness, and shortness of breath. He was diagnosed with acute respiratory distress syndrome due to COVID-19 and received oxygen and steroids during a one-month hospital stay. After discharge, he continued steroids and home oxygen therapy for nearly two years. CT scans revealed bronchiectasis and ground glass opacities related to COVID-19. He developed pulmonary nodules and M. intracellulare infection, which were treated with rifampicin, ethambutol, and azithromycin. After six months of treatment, the patient showed clinical and radiological improvement (AU)

Un hombre de 69 años con antecedentes de miocardiopatía hipertrófica y trastorno depresivo mayor acudió a urgencias por fiebre, debilidad y dificultad respiratoria. Se le diagnosticó síndrome de distrés respiratorio agudo debido a COVID-19 y fue ingresado en planta de neumología, donde recibió oxígeno y esteroides durante 1 mes. Después del alta continuó con esteroides y oxigenoterapia domiciliaria durante casi 2 años. Las tomografías objetivaron bronquiectasias y opacidades en vidrio deslustrado relacionadas con la COVID-19. Desarrolló nódulos pulmonares e infección por Mycobacterium intracellulare, siendo tratado con rifampicina, etambutol y azitromicina. Después de 6 meses de tratamiento, el paciente mostró mejoría clínica y radiológica (AU)

Disseminated coinfection with Mycobacterium Avium complex and Mycobacterium Kansasii in a patient with idiopathic CD4+ lymphocytopenia: A case report.

Simultaneously disseminated coinfection with two species of nontuberculous mycobacteria (NTM) is extremely rare and had been reported only in immunocompromised individuals. Here, we report a 59-year-old Thai man, previously healthy. He presented with a 2-month history of prolonged fever, constitutional symptoms, and hepatosplenomegaly. His chest and abdomen computed tomography illustrated multiple enlarged mediastinal lymph nodes accompanied with multifocal crazy-paving appearance in both lungs and hepatosplenomegaly. Endobronchial ultrasound-guided transbronchial needle aspiration was performed on the mediastinal nodes. The pathologic findings were necrotizing granulomatous lymphadenitis with numerous AFB-positive bacilli. Blood culture subsequently isolated M. intracellulare, while BAL and lymph node culture isolated M. intracellulare and M. kansasii, which confirmed species by multiplex PCR and 16s rRNA sequencing. Idiopathic CD4+ lymphocytopenia (ICL) was diagnosed as the cause of secondary immune deficiency. Intravenous imipenem, amikacin, and azithromycin were administered as an empirical antibiotic regimen for 4 weeks, then substituted to oral rifampicin, clarithromycin, moxifloxacin, and ethambutol as definitive regimen. Unfortunately, it was found that he had died unexpectedly at home after 4 months of treatment, possibly related to this illness. In our view, patients with severe disseminated NTM disease should be evaluated to explore a secondary immune deficiency disorder. An ICL is a rare heterogenous syndrome but should be considered.

Haemorrhagic Mycobacterium avium complex pericarditis presenting with cardiac tamponade in an immunocompetent woman.

A young woman in her mid-40s was referred by her primary care physician for fever, worsening shortness of breath, pleuritic chest pain and tachycardia. CT angiogram of the chest revealed a large pericardial effusion. Echocardiogram confirmed tamponade physiology despite her being haemodynamically stable. She had an emergency pericardiocentesis which revealed evidence of a haemorrhagic pericardial effusion. However, the patient was still symptomatic after treatment and had to undergo video-assisted thoracoscopic surgery with a pericardial window and chest tube. Postoperatively, her fevers resolved. Pan-culture was initially negative, and all antibiotics were discontinued. Acid-fast bacilli cultures later grew Mycobacterium avium complex. She continued to have chest discomfort postoperatively, but follow-up CT of the chest 3 months postoperatively showed continued resolution of her pericardial effusion. The patient's symptoms improved, and she has had no recurrence of effusion without the need for anti-tuberculosis drugs.

Evaluation of a novel ELISA test using synthetic mycolic acid antigens for serodiagnosis of non-tuberculous mycobacterial (NTM) infections.

The diagnosis of non-tuberculous mycobacteria (NTM) is a particular challenge in people with cystic fibrosis. Current standard diagnostic approaches rely on serial sputum culture, which is resource demanding, dependent on patient expectoration and may be compromised by excessive decontamination, conventional bacterial overgrowth and masking by concomitant oral and nebulised antibiotics. An alternative rapid, reliable and inexpensive diagnostic method is therefore urgently needed. Serum of patients with Mycobacterium abscessus infection and chronic suppurative lung disease without NTM infection was tested against an array of novel synthetic mycolic acids, identical or similar to natural components of mycobacterial cell walls, and glycopeptidolipid (GPL)-core antigen, which has previously been investigated in Mycobacterium avium pulmonary infection. Diagnostic accuracy of individual antigens and combination of various antigens were calculated. An ELISA using individual trehalose dimycolates and GPL-core antigen was able to effectively distinguish serum from infected and non-infected individuals with a specificity of 88% and a sensitivity of up to 88%, which increased to 88% sensitivity and 93% specificity by combining several antigens in the test. These results suggest synthetic mycolic acid antigens, used individually or in combination with GPL-core antigen could be successfully used to distinguish patients with M. abscessus infection from disease controls.

Apoptosis Inhibitor of Macrophages Contributes to the Chronicity of Mycobacterium avium Infection by Promoting Foamy Macrophage Formation.

In Mycobacterium avium infections, macrophages play a critical role in the host defense response. Apoptosis inhibitor of macrophage (AIM), also known as CD5L, may represent a novel supportive therapy against various diseases, including metabolic syndrome and infectious diseases. The mechanisms of AIM include modulating lipid metabolism in macrophages and other host cells. We investigated the role of AIM in M. avium infections in vitro and in vivo. In a mouse model of M. avium pneumonia, foamy macrophages were induced 6 wk after infection. The bacteria localized in these macrophages. Flow cytometric analysis also confirmed that the percentage of CD11chighMHCclassIIhigh interstitial and alveolar macrophages, a cell surface marker defined as foamy macrophages, increased significantly after infection. AIM in alveolar lavage fluid and serum gradually increased after infection. Administration of recombinant AIM significantly increased the number of bacteria in the lungs of mice, accompanied by the induction of inflammatory cytokine and iNOS expression. In mouse bone marrow-derived macrophages, the mRNA expression of AIM after M. avium infection and the amount of AIM in the supernatant increased prior to the increase in intracellular bacteria. Infected cells treated with anti-AIM Abs had fewer bacteria and a higher percentage of apoptosis-positive cells than infected cells treated with isotype control Abs. Finally, AIM in the sera of patients with M. avium-pulmonary disease was measured and was significantly higher than in healthy volunteers. This suggests that AIM production is enhanced in M. avium-infected macrophages, increasing macrophage resistance to apoptosis and providing a possible site for bacterial growth.

M ycobacterium avium complex genomics and transmission in a London hospital.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are environmental microorganisms and opportunistic pathogens in individuals with pre-existing lung conditions such as cystic fibrosis (CF) and non-CF bronchiectasis. While recent studies of Mycobacterium abscessus have identified transmission within single CF centres as well as nationally and globally, transmission of other NTM species is less well studied. METHODS: To investigate the potential for transmission of the Mycobacterium avium complex (MAC) we sequenced 996 isolates from 354 CF and non-CF patients at the Royal Brompton Hospital (London, UK; collected 2013-2016) and analysed them in a global context. Epidemiological links were identified from patient records. Previously published genomes were used to characterise global population structures. RESULTS: We identified putative transmission clusters in three MAC species, although few epidemiological links could be identified. For M. avium, lineages were largely limited to single countries, while for Mycobacterium chimaera, global transmission clusters previously associated with heater-cooler units (HCUs) were found. However, the immediate ancestor of the lineage causing the major HCU-associated outbreak was a lineage already circulating in patients. CONCLUSIONS: CF and non-CF patients shared transmission chains, although the lack of epidemiological links suggested that most transmission is indirect and may involve environmental intermediates or asymptomatic carriage in the wider population.

Mycobacterium avium Pleurisy with Bronchopleural Fistula Resulting in Rapidly Progressive Respiratory Failure Diagnosed by Transbronchial Autopsy.

Nontuberculous mycobacterial lung disease usually manifests as a chronic pulmonary infection. We herein report a fatal case of Mycobacterium avium pleurisy in a man with a refractory bronchopleural fistula that led to rapidly progressive pneumonia. A post-mortem transbronchial biopsy was performed. Histopathology revealed an acute lung injury pattern and epithelioid granulomas. Variable number tandem repeat analyses and drug susceptibility testing revealed Mycobacterium avium had acquired macrolide resistance during chemotherapy with rifampicin, ethambutol, and clarithromycin. Clinicians should be aware that Mycobacterium avium pleurisy with bronchopleural fistula can lead to fatal pneumonia, especially in patients with persistently positive cultures despite multidrug treatment.

A case report: Infection-related glomerulonephritis and mantle cell lymphoma due to mycobacterium avium complex infection.

RATIONALE: Mycobacterium avium complex (MAC) infection is common in lung, liver and skin. However, MAC presenting with peritonitis is uncommon and is particularly rare in immunocompetent patients. We report a case of infection-associated glomerulonephritis and mantle cell lymphoma caused by peritonitis due to MAC. PATIENT CONCERNS: We report a case of a 73-year-old elderly man with fever and abdominal pain for 2 days and gradually developed anuria, ascites, and abdominal lymphadenopathy. DIAGNOSES: The initial diagnosis was peritonitis and acute renal failure. There was no significant relief of symptoms after empirical anti-infective therapy and hemodialysis. infection-associated glomerulonephritis, mantle cell lymphoma, and peritonitis due to MAC were diagnosed by renal biopsy, abdominal lymph node biopsy, and metagenomics next-generation sequencing. INTERVENTIONS: The patient received empirical antibiotic therapy, hemodialysis, and anti-MAC therapy. OUTCOMES: Unfortunately, the patient eventually died of septic shock after the 21st day of admissiom. LESSONS: Early diagnosis of MAC infection is essential. When the cause of fever is unknown, metagenomics next-generation sequencing can be considered.

Adult acetonemic vomiting complicated with low body weight in a subject with Mycobacterium avium complex pulmonary disease: a case report.

Pulmonary diseases often cause significant health issues and nutritional disorders. Weight loss and malnutrition are related to the severity of obstructive disorders. Therefore, patients with such conditions often experience low nutritional energy. Acetonemic vomiting is caused by acetonemic syndrome. Previously, it was believe that acetonemic vomiting was observed only in childhood. However, it was recently suggested that acetonemic vomiting can also occur in adults. It is also considered that acetonemic vomiting can occur in subjects with low body weight because stored carbohydrate levels are reduced and fats are mainly used for energy. Consequently, large amounts of acetone are produced, ultimately resulting in nausea and vomiting. In this study, we report a case of adult acetonemic vomiting complicated by low body weight in a subject with Mycobacterium avium complex pulmonary disease.

Periocular Infection of Mycobacterium avium Complex in a Patient with Interferon-γ Autoantibodies: A Case Report.

The neutralizing anti-interferon-γ autoantibody (nAIGA)-associated immunodeficiency is an emerging entity frequently associated with the nontuberculosis mycobacterium (NTM) infection and other opportunistic infections. We present a female patient with a mysterious periocular Mycobacterium avium complex (MAC) infection, accompanied by sequential opportunistic infections including Salmollelosis and herpes zoster infection. Her condition stabilized after long-term antimycobacterial treatment. Nevertheless, neutralizing anti-interferon-γ autoantibody was found in her serum, which was compatible with the scenario of adult-onset immunodeficiency.