Recurrence of pulmonary Mycobacterium avium complex disease due to endogenous reactivation

Taga, Shu; Yagi, Tetsuya; Uchiya, Kei-ichi; Shibata, Yuichi; Hamaura, Hiromitsu; Nagao, Taku; Hayashi, Yuta; Nikai, Toshiaki; Ogawa, Kenji

doi:10.1099/jmmcr.0.000935

Cited by 3 publications

(2 citation statements)

References 8 publications

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“…Evidence for the existence of MAC recurrence is relatively recent, and its pathogenesis has not been studied as well as that of TB. Recently, there have been several case reports suggesting the possibility of MAC reactivation based on the genomic identity between initial isolates and recurrent isolates after chemotherapy [ 25 , 26 ]. In addition, a population-based national survey in the United States revealed that positive result rates for MAC skin tests peak in young adults and decrease in older populations [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Experimental Reactivation of Pulmonary Mycobacterium avium Complex Infection in a Modified Cornell-Like Murine Model

et al. 2015

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The latency and reactivation of Mycobacterium tuberculosis infection has been well studied. However, there have been few studies of the latency and reactivation of Mycobacterium avium complex (MAC), the most common etiological non-tuberculous Mycobacterium species next to M. tuberculosis in humans worldwide. We hypothesized that latent MAC infections can be reactivated following immunosuppression after combination chemotherapy with clarithromycin and rifampicin under experimental conditions. To this end, we employed a modified Cornell-like murine model of tuberculosis and investigated six strains consisting of two type strains and four clinical isolates of M. avium and M. intracellulare. After aerosol infection of each MAC strain, five to six mice per group were euthanized at 2, 4, 10, 18, 28 and 35 weeks post-infection, and lungs were sampled to analyze bacterial burden and histopathology. One strain of each species maintained a culture-negative state for 10 weeks after completion of 6 weeks of chemotherapy, but was reactivated after 5 weeks of immunosuppression in the lungs with dexamethasone (three out of six mice in M. avium infection) or sulfasalazine (four out of six mice in both M. avium and M. intracellulare infection). The four remaining MAC strains exhibited decreased bacterial loads in response to chemotherapy; however, they remained at detectable levels and underwent regrowth after immunosuppression. In addition, the exacerbated lung pathology demonstrated a correlation with bacterial burden after reactivation. In conclusion, our results suggest the possibility of MAC reactivation in an experimental mouse model, and experimentally demonstrate that a compromised immune status can induce reactivation and/or regrowth of MAC infection.

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Section: Discussionmentioning

confidence: 99%

Experimental Reactivation of Pulmonary Mycobacterium avium Complex Infection in a Modified Cornell-Like Murine Model

et al. 2015

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“…The timing of the infection suggests that chemotherapy unmasked the dormant MAC bacteria or enabled re-infection. Since MAC is ubiquitous in the environment, endogenous reactivation is difficult to confirm ( 14 , 15 ). However, experimental reactivation of latent pulmonary MAC infection has been demonstrated in a mouse model ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Initial Treatment Adjustments and Complications in Ovarian Cancer Patient With Inborn Error of Immunity

Mammadova¹,

Redden²,

Cruz³

et al. 2022

Front. Oncol.

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BackgroundPatients with inborn errors of immunity (IEI) have increased risk of developing cancers secondary to impaired anti-tumor immunity. Treatment of patients with IEI and cancer is challenging as chemotherapy can exacerbate infectious susceptibility. However, the literature on optimal cancer treatment in the setting of IEI is sparse.ObjectivesWe present a patient with specific antibody deficiency with normal immunoglobins (SADNI), immune dysregulation (ID), and stage III ovarian carcinoma as an example of the need to modify conventional treatment in the context of malignancy, IEI, and ongoing infections.MethodsThis is a retrospective chart review of the patient’s clinical manifestations, laboratory evaluation and treatment course.ResultsOur patient is a female with SADNI and ID diagnosed with stage III ovarian carcinoma at 60 years of age. Her ID accounted for antinuclear antibody positive (ANA+) mixed connective tissue diseases, polyarthralgia, autoimmune neutropenia, asthma, autoimmune thyroiditis, and Celiac disease. Due to the lack of precedent in the literature, her treatment was modified with continuous input from infectious disease, allergy/immunology and oncology specialist using a multidisciplinary approach.The patient completed debulking surgery and 6 cycles of chemotherapy. The dosing for immunoglobulin replacement therapy was increased for prophylaxis. Chemotherapy doses were lowered for all cycles preemptively for IEI. The therapy included carboplatin, paclitaxel, bevacizumab, and pegfilgrastim. The patient completed six-months of maintenance medication involving bevacizumab.Her treatment course was complicated by Mycobacterium avium-complex (MAC) infection, elevated bilirubin and liver enzymes attributed to excessive immunoglobulin replacement therapy, and urinary tract infection (UTI) and incontinence.Cancer genetic analysis revealed no targetable markers and primary immunodeficiency gene panel of 407 genes by Invitae was unrevealing. Lab tests revealed no evidence of Epstein-Barr Virus (EBV) infection. Post-chemotherapy imaging revealed no evidence of cancer for 1 year and 4 months, but the disease relapsed subsequently. The patient’s lung scarring requires vigilance.ConclusionsOur patient with ovarian cancer and IEI required modified treatment and prevention of complications. In cases of IEI, optimal chemotherapy should be titrated to minimize immunosuppression yet treat cancer aggressively while decreasing the risk of infection with prophylactic antibiotics and prolonged post-treatment surveillance, including pulmonary evaluation.

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Recurrence of Disseminated Mycobacterium avium Complex Disease in a Patient with Anti-Gamma Interferon Autoantibodies by Reinfection

Nishimura¹,

Fujita-Suzuki²,

Yonemaru³

et al. 2015

J Clin Microbiol

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jWe report a case of recurrent disseminated Mycobacterium avium complex (DMAC) disease with anti-gamma interferon autoantibodies. To our knowledge, this is the first reported case caused by reinfection with a separate isolate of M. avium. DMAC disease activity was monitored using serum IgG antibody titers against lipid antigens extracted from a MAC strain. CASE REPORTA 65-year-old woman was admitted to an outside hospital with subcutaneous panniculitis. Chest radiography revealed infiltration of the right upper lobe, and Mycobacterium avium was cultured from respiratory secretions. The patient was transferred to Keio University Hospital for definitive diagnosis and treatment. On admission, the patient's chief complaint was severe cough. She had a temperature of 38.3°C and marked hepatosplenomegaly on examination. The white blood cell (WBC) count and alkaline phosphatase (ALP) concentration were 36,100/l and 1,771 IU/ liter, respectively. Human immunodeficiency virus (HIV) antibody testing with an enzyme immunoassay was negative. Chest computed tomography (CT) showed an infiltrate in the right upper and middle lobes of the lung with angiogram sign and bilateral pleural effusions. M. avium was isolated from multiple samples, including sputum, pleural effusion, bronchoalveolar lavage fluid, bone marrow, and liver biopsy tissues. A bone marrow biopsy showed inflammation with granulomata. This case satisfied the diagnostic criteria for nontuberculous mycobacterial disease established by the American Thoracic Society (ATS) and the Infectious Disease Society of America (IDSA) (1), and we diagnosed this patient with disseminated Mycobacterium avium complex (DMAC) disease. Antimycobacterial therapy was initiated with four antibiotics: rifampin (RFP) at 450 mg/day, ethambutol (EB) at 750 mg/day, clarithromycin (CAM) at 800 mg/day, and kanamycin (KM) at 750 mg three times per week. After the initiation of antimycobacterial therapy, the WBC and ALP concentration were decreased compared with the values on admission. Pleural effusions decreased, and the pulmonary infiltrates improved. The patient was discharged on day 84 after admission. Two months after discharge, the WBC and ALP concentration had decreased to 6,800/l and 474 IU/liter. KM was switched to levofloxacin (LVX) at 400 mg/day due to concern about the cumulative dose approaching 40 g. M. avium was not isolated from any of the sputum cultures after discharge, and antimycobacterial therapy (EB, 750 mg/day; CAM, 800 mg/day; RFP 450 mg/day; and LVX, 400 mg/ day) was continued for approximately 2 years. Six months after the cessation of therapy, the patient again felt fatigued and feverish. The WBC and ALP concentration were again elevated, and she was readmitted to Keio University Hospital 9 months after the cessation of therapy (30 months after her first discharge). On readmission, the WBC and ALP concentration were elevated to 13,900/l and 497 IU/liter, respectively. A bone marrow biopsy was performed, and M. avium was again isolated from her bone marrow. Abdominal m...

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Recurrence of pulmonary Mycobacterium avium complex disease due to endogenous reactivation

Cited by 3 publications

References 8 publications

Experimental Reactivation of Pulmonary Mycobacterium avium Complex Infection in a Modified Cornell-Like Murine Model

Experimental Reactivation of Pulmonary Mycobacterium avium Complex Infection in a Modified Cornell-Like Murine Model

Case Report: Initial Treatment Adjustments and Complications in Ovarian Cancer Patient With Inborn Error of Immunity

Recurrence of Disseminated Mycobacterium avium Complex Disease in a Patient with Anti-Gamma Interferon Autoantibodies by Reinfection

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