Mycobacterium Avium Complex Infection Research Articles

S1773 Not Your Typical Diarrhea: A Case of Disseminated MAC in a Solid Organ Transplant Recipient

INTRODUCTION: Mycobacterium avium complex (MAC) colitis is a rare complication of immunosuppression in solid organ transplant (SOT) recipients. Here, we describe a case of disseminated MAC infection with colitis following simultaneous pancreas-kidney (SPK) transplantation. CASE DESCRIPTION/METHODS: A 54-year-old female was admitted to the hospital with a two-month history of watery diarrhea, intermittent nausea and unintentional weight loss of 40-pounds. She was recently discharged after a prolonged hospital stay for management of acute diarrhea and was diagnosed with recurrent Clostridium difficile Infection (CDI) that required multiple courses of fidaxomicin as she was intolerant to vancomycin. Past medial history included SPK transplant 4 years ago complicated by allograft rejection, CMV viremia and recurrent CDI. Her immunosuppressive regimen included mycophenolic acid, sirolimus, prednisone, and tacrolimus with therapeutic range drug levels. Laboratory examination was remarkable for leukopenia of 1.7 × 109/L with absolute neutrophil count (ANC) of 1300 cells/µL and otherwise normal chemistries. Initial infectious work-up unremarkable including CMV PCR, BK Virus PCR, C diff toxin and antigen and infectious stool studies. Computed tomography showed mild esophageal thickening without any colitis. Colonoscopy showed few patchy erosions dispersed throughout the colon. Histologic examination of random colon biopsies revealed poorly formed granulomas that stained positively for acid fast bacilli (AFB). Esophagogastroduodenoscopy was unremarkable except LA grade D esophagitis and biopsies were obtained from the duodenum. Interestingly, these duodenal biopsies also showed granulomas that stained positive for AFB. AFB culture performed on all specimens was positive for MAC. MAC was also isolated from urine and stool cultures that were reported later. Patient was started antimicrobial therapy with ethambutol, rifampin, and azithromycin guided by infectious disease specialist with resolution of diarrhea and weight gain. DISCUSSION: MAC infections are well established in acquired immunodeficiency virus infection, but remain rarely reported in SOT recipients. Moreover, disseminated MAC presenting as diarrhea is even more uncommon. The causes of diarrhea are exhaustive in patients on immunosuppression and hence it is important to keep MAC in the differential as its diagnosis is challenging and requires tissue sampling with culture and gene sequencing. Antimicrobials provide effective treatment and eradication.

PULMONARY ALVEOLAR PROTEINOSIS IN MYELODYSPLASTIC SYNDROME SECONDARY TO GATA-2 MUTATION (MONOMAC SYNDROME)

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: The majority of the cases of pulmonary alveolar proteinosis (PAP) occur in patients due to autoimmunity with the GM-CSF antibody. We present here a case of a 29-year-old female with GATA-2 mutation (monoMAC) syndrome who presented with dyspnea and was diagnosed with secondary PAP due to myelodysplastic syndrome. CASE PRESENTATION: A 29-year-old female presented to the hospital with the chief complaint of a nonproductive cough for 2 weeks associated with difficulty in breathing with exertion and intermittent fever. She had a history of heterozygous mutation for GATA-2 and was under treatment at a tertiary care center for early Myelodysplastic syndrome secondary to 9q34 deletion. Her medical history was extensive including Mycobacterium avium intracellulare (MAC) Pneumonia and bacteremia diagnosed 8 months before the presentation and was on azithromycin, ethambutol, and rifabutin for it to complete a total of 12 months of treatment. On presentation, she was febrile at 103 degrees Fahrenheit, tachycardiac at 135 beats per minute and saturating 88% on room air. She was placed on 4 L of oxygen by nasal cannula. Labs showed a WBC count of 8.4 10*3/uL (normal 4.0 - 12.0 10*3/uL) with differential showing a low monocyte count at <1 % (normal 2-8 %). Computed Tomography angiogram was obtained which ruled out a pulmonary embolism but showed diffuse and bilateral alveolar and interstitial pulmonary opacification. She had an extensive infectious, autoimmune, metabolic and cardiovascular workup which was all negative. So, bronchoscopy with bronchoalveolar lavage was obtained which showed an exudative effusion with 84 Polymorphonuclear cells, 2 Lymphocytes, 8 Histiocytes, 6 Eosinophils. BAL fluid was negative for respiratory viral PCR, AFB, fungal culture and bacterial culture, galactomannan and Pneumocystis culture. Cytology was also negative for pathogens or malignant cells. Post-Bronchoscopy the patient’s respiratory status improved, and she was weaned off of the oxygen. Pulmonary function tests (PFT) were also obtained there which revealed a non-specific ventilatory defect with decreased Diffusion lung capacity for Carbon monoxide (DLCO). A lung biopsy was obtained there confirming the diagnosis of pulmonary alveolar proteinosis (PAP). The patient had negative anti-GM-CSF antibodies indicating GATA-2 deficiency as the cause of PAP. The patient is scheduled to get a repeat full lung bronchoalveolar lavage and is currently being evaluated for a lung transplant. DISCUSSION: GATA-2 mutation is identified in cases of PAP secondary to hematological malignancies. Whole lung lavage is the standard of care. Treatment of the hematological malignancy may treat the PAP. There is no evidence of corticosteroids in the treatment of secondary PAP. CONCLUSIONS: Clinicians should be mindful of PAP in treating patients with hematological malignancies with respiratory distress. Reference #1: Ishii H, Seymour JF, Tazawa R, Inoue Y, Uchida N, Nishida A, et al. Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan. BMC Pulm Med. 2014;14:37. Reference #2: Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med 2002; 166: 215–235. Reference #3: Milleron BJ, Costabel U, Teschler H, et al. Bronchoalveolar lavage cell data in alveolar proteinosis. Am Rev Respir Dis 1991; 144: 1330–1332. DISCLOSURES: No relevant relationships by Fazal Raziq, source=Web Response No relevant relationships by Muhammad Usama, source=Web Response

COUGH-INDUCED DIFFUSE BRONCHIAL HEMORRHAGE

SESSION TITLE: Medical Student/Resident Procedures Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Bleeding from the tracheobronchial tree is usually caused by neoplasms, bronchitis, bronchiectasis, mucosal infections, and/or iatrogenic mucosal erosions. We present a rare case of petechial tracheobronchial hemorrhage developing after a severe bout of cough. CASE PRESENTATION: An 81-year-old male with past medical history of Acquired immunodeficiency syndrome (AIDS), combined pulmonary fibrosis and emphysema, pulmonary hypertension, and chronic hypoxemia on supplemental oxygen (3 L/min), presented with gradually worsening dyspnea and non-productive cough over 6 months. Computed tomography (CT) scan of the chest showed a right upper lobe cavitary lesion for which further evaluation with diagnostic flexible fiberoptic bronchoscopy was planned. His home medications included low dose aspirin (81 mg) daily for the primary prevention of cardiovascular disease. He did not have any prior history of hemoptysis or coagulopathy. The patient received aerosolized topical anesthesia with nebulized lidocaine orally prior to bronchoscopy after which he developed a strong coughing fit. Patient was intubated with a laryngeal mask and flexible bronchoscopy was performed under monitored anesthesia care using Propofol. Inspection of the airways incidentally showed numerous mucosal petechiae with oozing of blood in the entire tracheobronchial tree distal to the vocal cords [Figure 1]. Patient was admitted due to worsening hypoxia and hemoptysis post procedure. He had mild hemoptysis for the next two days after which it resolved without any intervention. Broncho alveolar lavage cultures showed Mycobacterium avium intracellulare complex for which he was treated. DISCUSSION: We describe an unusual case of diffuse bronchial hemorrhage that, given the clinical course, developed due to severe coughing fit immediately prior to bronchoscopy. Only a few cases of cough induced diffuse bronchial hemorrhage, also called as the "hemorrhagic bronchial mucosa syndrome", have been previously reported [1-3]. The presence of mucosal petechiae with evidence of bleeding is a characteristic finding and usually improves with conservative management. It has been postulated that high intrathoracic pressures during coughing can increase intravascular pressure resulting in local vessel damage and bleeding [3]. Immunocompromised status due to AIDS, old age, use of aspirin, and pulmonary hypertension may have been additional risk factors predisposing to hemorrhage in this case. CONCLUSIONS: Diffuse bronchial hemorrhage or "hemorrhagic bronchial mucosa syndrome” is a rare complication that can occur during bronchoscopy due to severe coughing and measures to prevent coughing should be considered. Reference #1: Panjwani A. Hemorrhagic bronchial mucosa syndrome. The Egyptian Journal of Internal Medicine. 2015;27(4):151-153. Reference #2: Hira HS. Cough-induced Tracheobronchial Mucosal Bleeding. J Bronchology Interv Pulmonol. 2011;18(1):51-52. Reference #3: Milman N. Diffuse bleeding from the bronchial mucosa on flexible bronchoscopy in lung transplanted patients: 'the hemorrhagic bronchial mucosa syndrome'. Respiration. 2009;77(4):416-419. DISCLOSURES: No relevant relationships by Steven Shaw, source=Web Response No relevant relationships by Abhishek Singla, source=Web Response

A CASE OF MAC IN A PATIENT WITH CHRONIC SILICOSIS

SESSION TITLE: Medical Student/Resident Occupational and Environmental Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Our patient is a 32-year-old male with chronic silicosis who presented with one week of worsening dyspnea and cough in the setting of a 40 pound weight loss over 3 months. CASE PRESENTATION: The patient was diagnosed with silicosis in 2015 (Image 1) in the setting of prolonged work with cutting porous stone without use of PPE; he had a negative mycobacterial work-up then. He was lost to follow-up and continued to work until one week prior to this presentation. On hospital presentation he was found to be febrile, severely cachectic, using accessory muscles for respiration, and with fine bilateral inspiratory crackles diffusely. He was subsequently admitted to the ICU for hypercapnic and hypoxemic respiratory failure requiring non-invasive ventilation (NIV). CT findings suggested progressive massive fibrosis (PMF) with eggshell calcifications of mediastinal lymph nodes; however, a cavitary infectious process could not be ruled out (Image 2 and 3). He was started on empiric antibiotics for bacterial pneumonia. Laboratory testing revealed negative bacterial, fungal, and viral sputum/blood cultures. He showed marginal improvement in respiratory status after initiating NIV and completing antibiotics. Although the initial AFB sputum smears were negative, two weeks later two separate AFB cultures each grew Mycobacterium Avium Complex (MAC). He was fully weaned off NIV after starting anti-mycobacterial therapy. Given the imaging and his clinical improvement, this decompensation was thought to be secondary to PMF with MAC superinfection. DISCUSSION: Silicosis occurs following chronic occupational exposure to aerosolized silica from mining, stone cutting, or sandblasting. Patients often are asymptomatic despite abnormal x-ray findings. Imaging of chronic silicosis typically follows nodular patterns of inflammation (which was noted on our patient's initial diagnosis) and in more acute presentations ground-glass opacities and crazy paving have been described. Our patient's clinical presentation and CT findings of diffuse coalescent densities and cavitations led us to consider PMF and mycobacterial disease over simple silicosis. PMF is a rare, and in most cases irreversible, complication of silicosis defined as conglomeration of dense fibrosis preferentially involving the upper lung lobes. Eggshell calcifications of lymph nodes are often described. Mycobacterial infection is also a rare complication of silicosis, classically with mycobacterium tuberculosis (TB); however there have been many case reports with silicosis patients developing MAC infections. These mycobacterial infections present with constitutional and TB-like symptoms such as weight loss. CONCLUSIONS: Progressive massive fibrosis in silicosis is a rare complication that leads to severe structural lung disease and respiratory failure. Mycobacterial superinfection, including MAC, should be considered in decompensated patients with silicosis. Reference #1: Jiro Fujita,Takumi Kishimoto,Yuji Ohtsuki,Eriko Shigeto,Takayuki Ohnishi,Masahiro Shiode,Yasufumi Yamaji,Ichizo Suemitsu,Ichiro Yamadori,Shuji Bandoh,Kazutaka Nishimura,Toshiharu Matsushima,Toshihiko Ishida. Clinical features of eleven cases of Mycobacterium avium-intracellulare complex pulmonary disease associated with pneumoconiosis. Respir Med. 2004 Aug;98(8):721-5. DISCLOSURES: No relevant relationships by Neel Bhan, source=Web Response No relevant relationships by Nicola Hanania, source=Web Response No relevant relationships by Lauren Nicholas Herrera, source=Web Response No relevant relationships by Hal Zhang, source=Web Response

Role of fluorescence in situ hybridization in detecting mycobacterium avium complex presenting as fever in treatment failure HIV

A 49-year-old male HIV positive patient on treatment failure presented with complaints of fever and dysphagia of three weeks duration and later on developed cervical lymphadenopathy along with severe vomiting and abdominal pain. Liver function tests were found to be worsening with severe drop in CD4 counts. An extensive workup for pyrexia was done. FNAC and biopsy of lymph node showed features suggestive of granulomatous lymphadenitis. CBNAAT of the lymph node aspirate was negative for MTB. Blood culture and lymph node cultures were negative for Mycobacterium Avium Complex (MAC). MAC was however, finally detected and reported positive on Fluorescence in Situ Hybridization (FISH) of the cervical lymph node aspirate. Prompt treatment for MAC was initiated with Ethambutol 800 mg OD and Azithromycin 500 mg OD following which fever spikes subsided and lymph node resolved. The Patient’s condition gradually improved and was discharged shortly with a good recovery on subsequent follow ups.Fever is one of the common symptoms in patients with MAC infection. Some other clinical manifestations include weight loss, hepatosplenomegaly and intra-abdominal lymphadenopathy. Diagnostic evaluation should be aggressive.As there is a high risk for MAC infection in advanced HIV cases with poor HAART compliance, FISH can be a valuable and effective diagnostic tool in early detection and treatment of MAC.

Heterologous Boosting With Listeria-Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection.

While Baccillus Calmette-Guerin (BCG) is used worldwide, tuberculosis (TB) is still a global concern due to the poor efficacy of BCG. Novel vaccine candidates are therefore urgently required. In this study, two attenuated recombinant Listeria strains, LMΔ-msv and LIΔ-msv were constructed by deletion of actA and plcB and expression of a fusion protein consisting of T cell epitopes from four Mycobacterium tuberculosis (Mtb) antigens (Rv2460c, Rv2660c, Rv3875, and Rv3804c). The safety and immunogenicity of the two recombinant strains were evaluated in C57BL/6J mice. After intravenous immunization individually, both recombinant strains entered liver and spleen but eventually were eliminated from these organs after several days. Simultaneously, they induced antigen-specific cell-mediated immunity, indicating that the recombinant Listeria strains were immunogenic and safe in vivo. LMΔ-msv immunization induced stronger cellular immune responses than LIΔ-msv immunization, and when boosted with LIΔ-msv, antigen-specific IFN-γ CD8+ T cell responses were notably magnified. Furthermore, we evaluated the protection conferred by the vaccine candidates against mycobacterial infection via challenging the mice with 1 × 107 CFU of BCG. Especially, we tested the feasibility of application of them as heterologous BCG supplement vaccine by immunization of mice with BCG firstly, and boosted with LMΔ-msv and LIΔ-msv sequentially before challenging. Combination immune strategy (LMΔ-msv prime-LIΔ-msv boost) conferred comparable protection efficacy as BCG alone. More importantly, BCG-vaccinated mice acquired stronger resistance to Mycobacterial challenge when boosted with LMΔ-msv and LIΔ-msv sequentially. Our results inferred that heterologous immunization with Listeria-based recombinant strains boosted BCG-primed protection against pulmonary mycobacterial infection.

Disseminated Mycobacterium avium complex infection as a differential diagnosis of tuberculosis in HIV patients.

BACKGROUND: Disseminated Mycobacterium avium complex infection (DMAC) has symptoms and microscopic findings similar to those of TB in HIV patients. To inform a clinical algorithm-based differential diagnosis, we aimed to characterise the clinical features of DMAC.METHODS: This was a retrospective cohort study of 192 HIV-positive patients with culture-confirmed mycobacterial infections hospitalised during 1996-2016 at a major HIV/AIDS treatment centre in Taiwan.RESULTS: HIV patients with DMAC (n = 58) had a three times higher 1-year mortality than those with TB (n = 98) (48.3% vs. 16.3%, P < 0.001). DMAC and TB were not distinguishable by the WHO TB screening criteria (fever, cough, night sweats or weight loss). Nevertheless, DMAC was characterised by a lower median CD4 count (5.0 cells/µL vs. 38.5 cells/µL, P < 0.001), lower median body mass index (BMI) (17.7 kg/m² vs. 19.7 kg/m², P = 0.002) and the absence of chest radiographic findings (P < 0.001). Simultaneous presence of CD4 <20 cells/µl, BMI <18.5 kg/m² and negative chest radiographic finding had a 98% specificity for diagnosing DMAC against TB or other types of mycobacterial infections.CONCLUSION: DMAC is an important differential diagnosis of TB in HIV patients. A simple rule based on CD4, BMI and chest radiography may inform the decision to start anti-DMAC treatment in patients with mycobacterial infection.

Molecular and Serological Footprints of Mycobacterium avium Subspecies Infections in Zoo Animals.

Background: Mycobacteria of the Mycobacterium avium complex (MAC) pose a significant risk to zoological collections. Mycobacterium avium subspecies paratuberculosis (MAP) is a member of MAC and the causative agent of Johne’s disease. Despite many reports in animals kept in zoological gardens, systemic surveillance has rarely been reported. Methods: In this study, archived serum samples collected from animal species at the Wilhelma Zoological and Botanical Gardens in Stuttgart, Germany, were screened for the presence of antibodies against MAC and MAP. In addition, molecular investigations were performed on necropsy, fecal, and environmental samples. Results: In total, 30/381 serum samples of various mammalian species were positive for MAC antibodies in ELISA, while one sample of a reticulated giraffe (Giraffa camelopardalis reticulata) was positive in MAP-specific ELISA. Samples from many species were positive in pan-Mycobacterium real-time PCR (40/43 fecal samples, 27/43 environmental samples, and 31/90 necropsy samples). Surprisingly, no sample was positive in the MAP-specific molecular assays. However, two environmental samples from primate enclosures were positive in Mycobacterium avium subspecies hominissuis (MAH)-specific real-time PCR. Conclusions: The results reveal serological indications of MAC infections in the zoological collection. However, the presence of a MAP-contaminated environment by a high-shedding individual animal or MAP-infected population is unlikely.

General Overview of Nontuberculous Mycobacteria Opportunistic Pathogens: Mycobacterium avium and Mycobacterium abscessus.

Nontuberculous mycobacteria (NTM) are emerging human pathogens, causing a wide range of clinical diseases affecting individuals who are immunocompromised and who have underlying health conditions. NTM are ubiquitous in the environment, with certain species causing opportunistic infection in humans, including Mycobacterium avium and Mycobacterium abscessus. The incidence and prevalence of NTM infections are rising globally, especially in developed countries with declining incidence rates of M. tuberculosis infection. Mycobacterium avium, a slow-growing mycobacterium, is associated with Mycobacterium avium complex (MAC) infections that can cause chronic pulmonary disease, disseminated disease, as well as lymphadenitis. M. abscessus infections are considered one of the most antibiotic-resistant mycobacteria and are associated with pulmonary disease, especially cystic fibrosis, as well as contaminated traumatic skin wounds, postsurgical soft tissue infections, and healthcare-associated infections (HAI). Clinical manifestations of diseases depend on the interaction of the host’s immune response and the specific mycobacterial species. This review will give a general overview of the general characteristics, vulnerable populations most at risk, pathogenesis, treatment, and prevention for infections caused by Mycobacterium avium, in the context of MAC, and M. abscessus.

Macrophage Signaling Pathways in Pulmonary Nontuberculous Mycobacteria Infections.

The incidence and prevalence of nontuberculous mycobacteria (NTM) lung disease is rising worldwide and accounts for most clinical cases of NTM disease. NTM infections occur in both immunocompetent and immunocompromised hosts. Macrophages are the primary host cells that initiate an immune response to NTM. Defining the molecular events that govern the control of infection within macrophages is fundamental to understanding the pathogenesis of NTM disease. Here, we review key macrophage host signaling pathways that contribute to the host immune response to pulmonary NTM infections. In this review, we focus primarily on NTM that are known to cause lung disease, including Mycobacterium avium intracellulare, M. abscessus, and M. kansasii.

Feature of Adhesins Produced by Human Clinical Isolates of Mycobacterium intracellulare, Mycobacterium intracellulare subsp. chimaera and Closely Related Species.

The Mycobacterium avium complex includes two closely related species, Mycobacterium avium and Mycobacterium intracellulare. They are opportunistic pathogens in humans and responsible for severe disease in a wide variety of animals. Yet, little is known about factors involved in their pathogenicity. Here, we identified, purified and characterized adhesins belonging to the heparin-binding hemagglutinin (HBHA) and laminin-binding protein (LBP) family from M. intracellulare ATCC13950 and examined clinical isolates from patients with different pathologies associated with M. intracellulare infection for the presence and conservation of HBHA and LBP. Using a recombinant derivative strain of M. intracellulare ATCC13950 producing green fluorescent protein and luciferase, we found that the addition of heparin inhibited mycobacterial adherence to A549 cells, whereas the addition of laminin enhanced adherence. Both HBHA and LBP were purified by heparin-Sepharose chromatography and their methylation profiles were determined by mass spectrometry. Patients with M. intracellulare infection mounted strong antibody responses to both proteins. By using PCR and immunoblot analyses, we found that both proteins were highly conserved among all 17 examined clinical M. intracellulare isolates from patients with diverse disease manifestations, suggesting a conserved role of these adhesins in M. intracellulare virulence in humans and their potential use as a diagnostic tool.

Extrapulmonary Mycobacterium avium complex infections in immunocompetent patients

The Mycobacterium avium complex (MAC) includes ubiquitous bacteria that typically cause infection in immunocompromised patients. This paper reviews the presentation, diagnosis, pathogenesis, and treatment of extrapulmonary MAC infections in immunocompetent patients by compiling information from case reports identified by a PubMed search. Mycobacterium avium complex infections in immunocompetent patients can present primarily with extrapulmonary symptoms, and this makes the diagnosis of MAC infection in these patients more difficult. The American Thoracic Society has not established criteria for the diagnosis of extrapulmonary MAC infections; testing for MAC should be based on clinical suspicion or after the exclusion of all other causative agents. Methods of testing should include molecular and biochemical tests, since these tests provide more definitive identification than routine cultures. Extrapulmonary presentations usually respond well to macrolide based multi-drug regimens started as soon as a MAC infection is identified. &#x0D; Key words: Mycobacterium avium, infection, diagnosis, treatment

Treatment of Nontuberculous Mycobacterial Pulmonary Infections

Sponsoring Organizations: The American Thoracic Society (ATS), the Infectious Diseases Society of America (IDSA), the European Respiratory Society, and

CapitalBio Mycobacterium real-time polymerase chain reaction detection test: Rapid diagnosis of Mycobacterium tuberculosis and nontuberculous mycobacterial infection

ObjectivesTo evaluate the accuracy of the CapitalBio Mycobacterium real-time polymerase chain reaction (RT-PCR) detection test for pulmonary Mycobacterium tuberculosis (MTB) and nontuberculous mycobacterial (NTM) infection. MethodsThis study analyzed 2,460 samples from patients with suspected pulmonary mycobacterial infection collected between 01 June 2018 and 31 July 2019. It aimed to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of the CapitalBio Mycobacterium detection test for MTB and NTM infections, and to evaluate its diagnostic accuracy compared with mycobacterial culture. ResultsThe sensitivity, specificity, PPV, NPV, and AUC of the CapitalBio Mycobacterium detection test for MTB was 83.0%, 79.9%, 80.8%, 82.2%, and 0.81, respectively. This was similar to the diagnostic accuracy of Xpert MTB/RIF for MTB and was significantly higher than that of smear. For pulmonary NTM infection, the sensitivity, specificity, PPV, NPV, and AUC of the test was 82.0%, 99.6%, 94.1%, 98.5%, and 0.91, respectively. The diagnostic accuracy of the CapitalBio Mycobacterium detection test was also significantly higher than that of smear for NTM. ConclusionsThe CapitalBio Mycobacterium detection test had good diagnostic accuracy for MTB and NTM infections. This is of great significance for the differential diagnosis of early pulmonary mycobacterial infection.

Different clinical features of patients with pulmonary disease caused by various Mycobacterium avium–intracellulare complex subspecies and antimicrobial susceptibility

ObjectivesCharacteristics of the Mycobacterium avium–intracellulare complex pulmonary disease (MAC-PD) caused by distinct subspecies remain uncertain. MethodsThis study was conducted from 2013–2015 in three hospitals in Taiwan. ResultsAmong the 144 patients with MAC-PD, 57 (39.6%), 37 (25.7%), 37 (25.7%), and 13 (9.0%) were infected with Mycobacterium intracellulare subspecies intracellulare (MIsI), Mycobacterium avium subspecies hominissuis (MAsH), Mycobacterium intracellulare subspecies chimaera (MIsC), and others, respectively. Patients with MAsH-PD were younger (p = 0.010) with higher human immunodeficiency virus infection rates (27.0%, 0.0%, 0.0%, and 7.7% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p < 0.001). Twenty-two (15.3%) patients reported spontaneous culture-negative conversion, but 15 (10.4%) and 33 (22.9%) patients developed radiographic progression and unfavorable outcomes, especially MAsH-PD. The susceptibility rates to clarithromycin and inhaled amikacin were both 98.6%. MAsH demonstrated the lowest rate of resistance to moxifloxacin (66.7%, 97.3%, 89.1%, and 92.3% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p = 0.001) and MIsI isolates had the highest rate of resistance to intravenous amikacin (25%, 13.5%, 38.2%, and 15.4% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p = 0.024). ConclusionsPulmonary disease caused by distinct MAC subspecies had different outcomes and drug susceptibility. The local prevalence of species needs to be monitored.

Characteristics of Circulating CD4+ T Cell Subsets in Patients with Mycobacterium avium Complex Pulmonary Disease.

Although prevalence of Mycobacterium avium complex pulmonary disease (MAC-PD) is increasing, limited data are available regarding vulnerability to Mycobacterium avium complex (MAC) infections. To understand the pathobiology of interaction between MAC and host-immunity, it is important to understand the characteristics for circulating T cells in terms of the immunological phenotype and functional correlates in MAC-PD. We aimed to characterize immunophenotype, cytokine profile, and immune inhibitory receptors of circulating CD4+ T cells in MAC-PD patients. We enrolled 71 MAC-PD and 20 control individuals. Flow cytometric analysis was performed to determine T cell subsets and immune checkpoint markers. Ex vivo cytokine productions in response to MAC were determined using enzyme-linked immunosorbent assay. The frequencies of CD4+ T cells and CD4+IL-17+ T cells decreased, while CD4+IL-4+ T cells and CD4+CD25+Foxp3+ T cells increased in peripheral blood mononuclear cells (PBMCs) of MAC-PD individuals upon MAC stimulation compared with those cells in healthy donor-PBMCs. Additionally, we found increased PD-1, CTLA-4, and TIM-3-expressing T cells in MAC- PD individuals in response to MAC-stimulation, indicating that suppressed T cell-mediated response is associated with the susceptibility to MAC infection. These results may help to explain impaired T cell-mediated responses and pave the way for better strategies to achieve protective immunity against MAC infection.

肺非結核性抗酸菌症の外科治療におけるCOPD assessment testの有用性と術後HRQOLの経過

肺非結核性抗酸菌症の外科治療におけるCOPD assessment testの有用性と術後HRQOLの経過

Clinical outcomes in Mycobacterium xenopi versus Mycobacterium avium complex pulmonary disease: A retrospective matched cohort study.

Mycobacterium xenopi is associated with the highest mortality among pulmonary nontuberculous mycobacterial (NTM) infections, but whether this is due to the infection or other factors is unclear. There is little information regarding outcomes among patients infected with M. xenopi versus other NTM species. We conducted a retrospective matched cohort study comparing M. xenopi pulmonary disease (Mx-PD) to M. avium complex (MAC)-PD. Patients were matched by sex, age, radiologic subtype, and presence of cavitation. Baseline clinical characteristics, treatment, and outcomes were compared using matched analyses. We identified 70Mx-PD cases: 29 fibrocavitary-type, 28 nodular-bronchiectatic-type, and 13 unclassifiable-type CT patterns, mean (SD) age 63 (13) years, and 54.3% (n=38) female. Median follow-up duration was longer in the Mx-PD cohort (1552 days versus 1035 days, p=0.01). Symptoms, radiologic phenotype, and pulmonary function were similar between groups although the Charlson Comorbidity Index was numerically higher in Mx-PD patients (3.6 versus 3.2, p=0.08). Rifamycins were used less frequently in Mx-PD (59.5% versus 85.7%, p=0.02). Although combined clinical and radiologic improvement was similar between the groups, successful treatment was more common with Mx-PD (40.5% versus 16.7%, p=0.02) owing to superior culture conversion (70.8% versus 33.3%, p=0.0001). Mortality 24 months after initiation of treatment was numerically but not statistically greater in the Mx-PD cohort (20.4% versus 10.3%, p=0.32). Among matched Mx-PD and MAC-PD patients, standard anti-mycobacterial treatment was significantly more likely to achieve culture conversion and successful treatment for Mx-PD patients. Mortality among Mx-PD patients was numerically, but not statistically higher, possibly explained by increased comorbidity burden.

Epidemiology and Risk Factors Associated with NTM Pulmonary and Extrapulmonary Infections in a High Tuberculosis Endemic Region

AbstractIntroduction: Non-tuberculous mycobacteria, although identified as pathogenic to humans long time ago, are emerging as the new threat in the past two decades. Even in tuberculosis endemic country such as India, they are being isolated from the clinical specimens more often than previously. This change in trend is of concern, because they are often misdiagnosed as Mycobacterium tuberculosis or even as drug-resistant tuberculosis. Objectives: A prospective, observational study was planned to identify the frequency and risk factors associated with pulmonary and extrapulmonary non-tuberculous mycobacterial (NTM) infections. Agreement between two commercially available molecular systems, namely GenoType Mycobacteria CM assay and matrix-assisted laser desorption/ionisation time of flight mass spectrometry (MALDI TOF MS) used in the identification of mycobacterial species is also analysed. Materials and Methods: NTM isolated from pulmonary and extrapulmonary clinical specimens over a period of 1½ year was included in the study. Patient demographics were collected, and the risk factors associated with NTM infections were analyzed. NTM grown on culture was speciated using GenoType Mycobacteria CM assay (HAIN Life Sciences, Germany) and MALDI TOF MS (bioMerieux, France). Drug-susceptibility tests were done for rapid-growing NTM using E-test (bioMerieux, France). Results: Eight hundred and fifty-four mycobacteria were isolated from 5009 specimens processed during the study period. Out of the mycobacteria grown, 74 (8.7%) were NTM and 780 (91.3%) were Mycobacterium tuberculosis complex. The NTM isolated from pulmonary specimens were 46 (62.16%) and from extrapulmonary sources were 28 (37.84%). The most common species isolated from pulmonary specimens was Mycobacterium intracellulare and from extrapulmonary specimens was Mycobacterium abscessus. Concordance between the two commercial assays used for the identification was 96.49%. The most common risk factor associated with pulmonary NTM was previous lung pathology, while with extrapulmonary NTM infection was previous surgical intervention. Drug-susceptibility tests for rapid growers showed amikacin and clarithromycin as the most active drugs in vitro. Conclusions: NTM plays a significant role in causing pulmonary and extrapulmonary infections even in our part of the country with high endemicity of tuberculosis. NTM has emerged as important pathogens even in the immunocompetent patients. There is a need for rapid diagnosis and susceptibility testing of NTM to aid physicians administer timely and appropriate treatment to the patients.

Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease.

The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.