MAI Infection Research Articles

Case of a 38-year-old man with NEMO deficiency syndrome complicated by marginal zone lymphoma

Here, we present a unique case of a 38-year-old man with history of Nuclear Factor-Kappa B Essential Modulator (NEMO) deficiency syndrome, whose course was complicated by marginal zone lymphoma. At 7 years of age, he was found to have MAI infection and throughout his life, developed further complications of MAI including osteomyelitis, intracranial lesions, adrenal abscesses, and cavitary pulmonary disease. Genetic testing revealed 1207 C-to-T mutation in NEMO, leading to R-for-C substitution at position 417 in the zinc finger domain. He has had a long history of recurrent viral and bacterial sinopulmonary infections since infancy continuing into adulthood, with over thirty lifetime episodes of serious pneumonia requiring hospitalizations, which has led to bronchiectasis.At 36 years of age, he presented to the hospital for five months of progressively worsening dyspnea and wheezing, hypoxemic respiratory failure, and a 15-pound weight loss. CT imaging demonstrated increased consolidation and nodularity, and sputum culture revealed methicillinsusceptible Staphylococcus aureus and Corynebacterium pneumonia treated with vancomycin. He was incidentally found to have a new 7.5 cm left periaortic lymph node conglomerate on CT abdomen/pelvis. Lymph node biopsy showed B-cell lymphoma with plasmacytic differentiation and with increased large cells, most concerning for marginal zone lymphoma. He received eight doses of rituximab as well as radiation therapy, with subsequent improvement on imaging. Following this diagnosis, lung biopsy was obtained, demonstrating nodular fibrosis in a primarily airwaycentered distribution with patchy, focal organizing pneumonia, most consistent with fibrosing chronic organizing pneumonia, treated with high dose prednisone. However, his course had since been complicated by increasingly frequent hospitalizations for acute on chronic hypoxemic respiratory failure corresponding with superimposed respiratory infectious as well as exacerbations of his organizing pneumonia.Hematopoietic stem cell transplantation was strongly considered as this would be a definitive treatment for his NEMO syndrome, as he has multiple severe complications of his NEMO deficiency syndrome. Unfortunately, after multidisciplinary discussions, he was ultimately considered to not be a candidate given his very poor pulmonary status. The patient was started on rituximab for his organizing pneumonia and continued on antibiotic prophylaxis with immunoglobulin replacement.

1346 CA 19-9: Elevation in Mycobacterium Avium-Intracellulare Infections

INTRODUCTION: Carbohydrate antigen 19-9 is usually associated with pancreatic malignancy. However, other causes as bronchiectasis can cause lab elevation. Here we present a case of an elevated CA 19-9 with pulmonary mycobacterium avium-intracellulare. CASE DESCRIPTION/METHODS: 66 year old HIV negative female with MAI (Figure 1) on Ethambutol, Rifampin, Azithromycin (started 4/2017, stopped 10/2017, restarted 1/2018) presented to clinic with complaints of epigastric pain with unintentional weight loss. She was started on proton pump inhibitor and H2 blocker therapy and underwent EGD and colonoscopy with biopsies positive for Helicobacter pylori. She received quadruple therapy with eradication on stool antigen. She complained of a mass in her supra-pubic region and given this with her weight loss and normal endoscopies, a CT Abdomen and Pelvis was performed which showed no hepato-biliary abnormalities but significant bladder distention (Figure 2). This resolved on its own prior to her seeing urology or coming in for follow up. A CA 19-9 remained elevated at 105, 94, and 111 during this time frame. DISCUSSION: Mycobacterium is a masquerader causing hydronephrosis to bronchiectasis, both seen in our patient, with the mechanism of CA 19-9 elevation unknown. Shin et al presented a patient with MAI and elevated CA 19-9 levels, which improved with treatment. 1 Studies have shown an elevated CA 19-9 may be from MAI infection or other causes of bronchiectasis, such as Chang et al in 2013. 2 Yamazaki et al compared CA 19-9 in patients with deteriorated (96.9) vs non-deteriorated (19.2) disease. 3 Hong and colleagues in their analysis showed that CA 19-9 could be elevated in patients with MAI and improved with treatment. 4 Here, we highlight the importance of a differential diagnosis of non-pancreatic etiologies for elevated CA 19-9 levels.

Genitourinary Tract Infection Due to Mycobacterium avium intracellulare Complex Infection in Pretransplant Setting With Recurrence Following Transplant: A Case Report

Genitourinary (GU) tract infection with Mycobacterium avium intracellulare complex (MAI) is very rare and, to our knowledge, has never been reported in the solid organ transplant literature. Case DescriptionA 61-year-old Somali-born woman had a history of liver cirrhosis due to chronic hepatitis C infection. She was diagnosed as having and treated for latent tuberculosis infection and GU tract infection due to MAI. She received a total of 17 months antimycobacterial therapy consisting of azithromycin, ethambutol, and moxifloxacin. Within 5 months of the initiation of antimicrobial therapy, there was documented sterilization of urine mycobacterial cultures. Liver and kidney transplant was performed 3 months after finishing the treatment course. One year following transplant, GU tract infection due to MAI recurred. She declined further diagnostic testing as well as mycobacterial therapy. She died 15 months following transplant for reasons not related to infections. ConclusionThe treatment of MAI infection in solid organ transplant candidates and recipients is challenging, and the duration of therapy in this population is not known. The recurrence of infection following transplant in this case may argue in favor of a duration that extends beyond the date of transplant. The combination of a fluoroquinolone and ethambutol may successfully prevent reactivation of tuberculosis in patients with history of latent tuberculosis infection and deserves further evaluation.

Emerging Side Effects of Programmed Cell Death 1 Ligand Inhibitors: MAC Infection and Nivolumab

SESSION TITLE: Non-Small Cell Lung Cancer SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Mycobacterium Avium Complex (MAC) is a ubiquitous environmental microorganism. In recent years, there has been an increase in disease incidence; it is not clear whether this reflects a real increase in infection rate or greater recognition resulting from more widespread awareness and advanced laboratory techniques. A potential reason for the MAC infection is the weakened immune system in aging population and the rise in the use of immunomodulating drugs. We hereby describe the first known case report of MAC infection in a patient with Non-Small Cell Lung Cancer (NSCLC) receiving Nivolumab (Opdivo) a programmed cell death 1 ligand inhibitor. CASE PRESENTATION: Our patient is an 83 years old gentleman with lung adenocarcinoma diagnosed in June 2011. He had received six cycles of Pemetrexed and Carboplatin and placed on maintenance therapy with Pemetrexed which was discontinued due side effects. The cancer progressed and the patient was placed on Opdivo with great response. At a follow up appointment, the patient presented with progressive fatigue, weight loss, and dry cough. On physical examination, the patient appeared chronically ill, with no specific respiratory exam findings. His chest was clear to auscultation without wheezing, rhonchi or crackles. Additionally, his laboratory results showed normal WBC count and differential. CT scan of the chest showed no progression of his cancer but revealed new nodular and small cavitary lesions with centrilobular nodularity in tree-in-bud distribution (figure 1). Subsequently the patient underwent bronchoscopy with diagnostic bronchoalveolar lavage which returned positive for MAI infection. The patient was placed on triple antibiotics and the Opdivo was placed on hold. At three months follow up, the patient showed significant improvement in his fatigue and weight and his cough had resolved. DISCUSSION: Despite the impressive benefits of the immune checkpoint blockade, its use can be hampered by the occurrence of serious adverse events including immune-related adverse events (irAEs) and opportunistic infections with potentially aggressive course and fatal outcome. With more indications and widespread use of these medications we will be encountering more of their side effects. Prompt diagnosis, discontinuation of the drug and starting antibiotics treatment is the key for successful treatment CONCLUSIONS: It is important to become aware of the possible infections that patient on current treatment with Opdivo (Nivolumab) could develop; it becomes important to keep in mind that MAC infections should be at the top of the list in the differential diagnosis if patient presents with symptoms such as cough, fever, severe fatigue. Reference #1: OPDIVO. Package insert. Princeton, NJ: Bristol Myers Squibb Company; 2016. DISCLOSURE: The following authors have nothing to disclose: Fernando Fuentes, Yousef Al-ahwel No Product/Research Disclosure Information

An association between pulmonary Mycobacterium avium-intracellulare complex infections and biomarkers of Th2-type inflammation

BackgroundThe rising incidence of pulmonary Mycobacterium avium-intracellulare complex (MAI) infection is unexplained but parallels the growing world-wide epidemic of allergic disease. We hypothesized an association between pulmonary MAI infection and Th2-type immune responses as seen in allergy.MethodsBiomarkers of patient Th2-type immune responses (peripheral blood eosinophil counts and serum IgE levels) were compared between patients with positive pulmonary samples for tuberculosis and non-tuberculous mycobacterial (NTM) infection. A further comparison of clinical characteristics, including respiratory co-morbidities, and biomarkers, was conducted between patients culturing MAI NTM and those culturing NTM other than MAI.ResultsPatients culturing NTM from pulmonary samples had significantly higher peripheral blood eosinophil levels than those culturing Mycobacterium tuberculosis. Furthermore, patients culturing MAI compared to those culturing NTM other than MAI had higher eosinophil counts (mean 0.29x109/L vs 0.15x109/L, p = 0.010) and IgE levels (geometric mean 138kU/L vs 47kU/L, p = 0.021). However there was no significant difference in the frequency of asthma between the two NTM groups.ConclusionsThere is an association between biomarkers of Th2-type immune responses and pulmonary MAI. Prospective and translational research could identify the direction of causation; and so determine whether our finding may be utilized within future management strategies for MAI.

Pulmonary Infections With Mycobacterium avium-intracellulare in Women With Confirmed or Suspected Malignancy

Background In the last 2 decades, there has been an increased interest in infections caused by nontuberculous mycobacteria (NTM). Mycobacterium avium complex is the most common PNTM in the United States. Pulmonary disease caused by MAI is often chronic and occurs particularly in the elderly, in women frequently without underlying lung disease. Although NTM infections are reported in patients with malignancy, few studies investigated the epidemiological, clinical, and radiological characteristics of pulmonary MAI infection in women with cancer. Materials and Methods We retrospectively reviewed medical and microbiologic records and radiographic findings of all female patients seen at the Moffitt Cancer Center in Tampa, Florida, with positive lung specimen cultures for MAI from January 1987 to January 2011. Microbiologic records included the cultures of expectorated sputum samples, bronchial wash or lavage, and lung biopsies. Radiographic findings obtained by high-resolution computed tomography permitted a classification of the lung MAI disease in 3 forms: cavitary, nodular bronchiectatic, and nodular form. Results A total of 46 patients met the inclusion criteria during a 24-year period. The median age at the time of diagnoses was 68 years. There were some patients who had an underlying cancer, an underlying chronic lung disease, and a comorbid condition. Cough was the most common pulmonary symptom in most of our patients. The most common radiologic finding was consistent with a single nodule. A few of the female patients were definable as Lady Windermere syndrome. Symptomatic improvement was seen in most of the patients with either a monotherapy or a combination therapy. Conclusions Physicians need to be aware of the possibility of coexisting pulmonary MAI in elderly women with cancer, principally breast and lung cancer, or chronic lung disease, with a chronic cough and a new nodule on the lung computed tomography scan. Early suspicion can lead to appropriate diagnosis, prompt therapy, and reduction of mortality.

Pharmacokinetics of chewed vs. swallowed raltegravir in a patient with AIDS and MAI infection: some new conflicting data.

BackgroundWhile HIV, AIDS and atypical Mycobacterium infections are closely linked, the use of Integrase-Inhibitor based cART, notably raltegravir-based regimens is more widespread. RAL should be double-dosed to 800 mg semi-daily in situation of rifampicin co-medication, because RAL is more rapidly metabolized due to rifampicin-induced Uridine-5’-diphosph- gluronosyl-transferase (UGT1A1). Recently, it was speculated that chewed RAL might lead to increased absorption, which might compensate the inductive effect of rifampicin-rapid metabolized RAL, as part of cost-saving effects in countries with high-tuberculosis prevalence and less economic power.MethodsWe report measurement of raltegravir pharmacokinetics in a 34-year AIDS-patient suffering from disseminated Mycobacterium avium infection with necessity of parenteral rifampicin treatment. RAL levels were measured with HPLC (internal standard: carbamazepine, LLQ 11 ng/ml, validation with Valistat 2.0 program (Arvecon, Germany)). For statistical analysis, a two-sided Wilcoxon signed rank test for paired samples was used.ResultsHigh intra-personal variability in raltegravir serum levels was seen. Comparable Cmax concentrations were found for 800 mg chewed and swallowed RAL, as well as for 400 mg chewed and swallowed RAL. While Cmax seems to be more dependent from overall RAL dosing than from swallowed or chewed tablets, increased AUC12 is clearly linked to higher RAL dosages per administration. Anyway, chewed raltegravir showed a rapid decrease in serum levels.ConclusionsWe found no evidence that chewed 400 mg semi-daily raltegravir in rifampicin co-medication leads to optimized pharmacokinetics. There is need for more data from randomized trials for further recommendations.

Successful endovascular treatment of three fusiform cerebral aneurysms with the Pipeline Embolization Device in a patient with dilating HIV vasculopathy

Dilating HIV vasculopathy can be a cause of ischemic and hemorrhagic stroke in patients with HIV. Although first identified in children, this condition is increasingly being recognized in adults and...

Overwhelming MAI and Pneumococcal Infection in a 19 Month Old Female with Normal IFNγRI Expression

Overwhelming MAI and Pneumococcal Infection in a 19 Month Old Female with Normal IFNγRI Expression

Activities of poloxamer CRL-1072 against Mycobacterium avium in macrophage culture and in mice.

Earlier studies reported that certain large hydrophobic poloxamer surfactants were able to inhibit the growth of Mycobacterium avium-M. intracellulare complex (MAI) in broth and to produce synergistic enhancement of the activity of rifampin. CRL-1072 was synthesized to have an optimal structure for antimicrobic effects and greater purity. Its MIC for MAI in broth was greater than 100 microg/ml. Surprisingly, its MIC for MAI growing in human U937 monocytoid cells was much lower, 5 microg/ml. A still lower concentration, 0.1 microg/ml, produced synergistic enhancement of the activities of clarithromycin, rifampin, amikacin, streptomycin, and clindamycin, but not isoniazid, against MAI infecting monocytoid cells. Mice tolerated injection of doses of CRL-1072 as high as 125 mg/kg of body weight. Pharmacokinetic analysis revealed that the copolymer had an elimination half-life of 60 h and suggested dosing regimens that might produce therapeutic concentrations in tissue. In a mouse model of acute MAI infection, CRL-1072 significantly enhanced the bactericidal activities of clarithromycin and rifampin when it was administered at 1.0 mg/kg intravenously (i.v.) three times per week. CRL-1072 given i.v. or orally also enhanced the bactericidal activity of clindamycin against MAI.

Negative images due to MAI infection detected in Papanicolaou‐stained duodenal brushing cytology

Atypical mycobacteriosis of the duodenum was diagnosed by duodenal brush cytology in a woman with AIDS. Smears were fixed in alcohol and stained by the method of Papanicolaou. The cytological characteristics of this disease have been described previously in other cytological specimens such as imprints or fine-needle aspirations stained with Diff-Quik or Wright's stain. We found that alcohol fixation and routine Papanicolaou staining allow observation of numerous foamy and striated macrophages (pseudo-Gaucher cells), as well as negative images both within the cytoplasm of the macrophages and in the background of smears in areas of air-drying artifact. These findings should suggest the diagnosis of atypical mycobacteriosis, and special staining techniques such as PAS and Ziehl-Neelsen are useful in corroborating it. This has not been previously described. Diagn. Cytopathol. 1998;19:462–464. © 1998 Wiley-Liss, Inc.

Involvement of HLA-DR+ Large Granular Lymphocytes in the Induction of Tumor Necrosis Factor by Mycobacterium avium-intracellulare Complex

This study shows that normal human large granular lymphocytes (LGL) secrete tumor necrosis factor (TNF) in response to Mycobacterium avium-intracellulare complex (MAI). Percoll density gradient fractionation of peripheral mononuclear cells showed TNF activity in the fractions corresponding to LGL and not T cells, even when 5% monocytes were added to the T lymphocytes for accessory function. TNF release was not abrogated by treatment of the crude LGL preparations with anti-Leu M3, -CD4, and -CD8 antibodies (Ab) plus complement (C), but was abrogated by anti-CD16 and -CD2 Ab, as expected. Interestingly, anti-HLA-DR monoclonal antibody (mAb) treatment significantly diminished TNF activity from LGL, but maintained natural killer (NK) cell function unmodified as opposed to CD2+ and CD16+ cell depletion. Panning studies demonstrated that TNF secretion upon MAI stimulation resided only in the HLA-DR+ LGL and not the DR- LGL population. These results indicate that normal fresh HLA-DR+ LGL, as well as monocytes, are also responsible for rapid TNF secretion during early MAI infection. These DR+ cells appear to be distinct from those expressing NK function.

Paraspinous Abscess With Mycobacterium avium-intracellulare in a Patient Without AIDS

This paper reports the case of a young woman with SLE whose paraspinous abscess due to Mycobacterium avium-intracellulare was metastatic to the breast. Surgical drainage and 18 months of treatment with rifampin, cycloserine, ethambutol, and streptomycin failed to eradicate the infection. This case illustrates that MAI infection can occur in patients not usually considered to be immunosuppressed and may be difficult to treat.

Endobronchial Mycobacterium avium-intracellulare Infection in a Patient with AIDS

The pulmonary manifestations of AIDS are well described in the medical literature; however, MAI infection presenting as an endobronchial lesion has not, to our knowledge, been reported in a patient with AIDS. We report a unique case of an AIDS patient who developed endobronchial polypoid lesions secondary to MAI infection. Complications resulting from these lesions included hemoptysis and later bronchiectasis.

Mycobacteremia in AIDS patients. Results of a prospective study.

The importance of blood cultures in diagnosing disseminated mycobacteriosis in AIDS patients was evaluated. Blood samples were screened for mycobacteria by culture and microscopic techniques. Mycobacteremia was proven in 20/136 (14.7%) AIDS patients, the agent being M. avium-M. intracellulare (MAI) in 16 cases and M. tuberculosis in four cases. The rate of cases with positive blood samples in disseminated MAI infection was 59.3% (16/27 cases) and in disseminated tuberculosis 57.1% (4/7 cases). To detect mycobacteria buffy-coat was slightly superior to lysated cell pellets, obtained by a lysis-centrifugation technique. In 4/16 cases with MAI bacteremia, the agent was proven by positive blood smears for acid-fast bacilli only; in these four patients MAI was demonstrated at other body sites. These results illustrate the diagnostic role of blood culture and its use in early diagnosis of disseminated mycobacteriosis, with microscopic examination of blood smears being an important adjunct.

HIV-disease and bone marrow changes: a study of 60 cases.

We report our experience of peripheral blood and bone marrow changes in patients with HIV disease. Abnormalities were most commonly seen in patients with advanced disease. In AIDS group IV patients (CDC classification) anaemia (92%) neutropenia (85%) monocytopenia (75%) and thrombocytopenia (61%) have their highest incidence, the reason being a combination of factors such as infection, myelosuppressive drugs and HIV infection itself. Bone marrow examinations were performed most commonly for microbiological culture (25%) and the investigation of anaemia (16%). Morphological changes in the bone marrow were non-specific and not pathognomic; however erythroid hypoplasia was found to be a distinctive feature associated with MAI infection. The procedure provided a high yield for microbiological culture, particularly in MAI infection.