Disseminated Mycobacterium Genavense Research Articles

Disseminated mycobacterium genavense infection with central nervous system involvement in an HIV patient: a case report and literature review

BackgroundImmunodeficient patients, particularly HIV patients, are at risk of opportunistic infections. Nontuberculous mycobacteria can cause severe complications in immunodeficient patients.Case PresentationWe describe a 57-year-old HIV patient, primarily presented with coughs and constitutional symptoms, with a unique Mycobacterium genavense abdominal, pulmonary, and central nervous system infection, accompanied by intracranial masses.ConclusionThe diagnosis of NTM, including M. genavense, must always be considered by clinicians in immunodeficient patients, especially those with HIV, who have a compromised immune system.

Disseminated Mycobacterium genavense infection in an otherwise healthy child: a clinical case and literature review

This paper presents the first clinical case of combined pulmonary and abdominal M. genavense infection in an otherwise healthy, immunocompetent child with an early treatment response and full recovery. The favorable outcome was determined by rapid microbiological diagnosis using up-to-date diagnostic methods followed by targeted antimicrobial therapy.

Sarcoid-like lesions obfuscating the diagnosis of disseminated Mycobacterium genavense infection in a patient with IL-12Rβ1-associated immunodeficiency

BackgroundSarcoidosis is a systemic inflammatory disease that is characterized by non-caseating epithelioid-cell granulomas upon histology. However, similar histological findings may also be seen with certain infections. Thus, differentiation from infection is pivotal to ensure appropriate treatment. Here, we present a case of a disseminated infection with Mycobacterium genavense owing to an interleukin 12 receptor subunit beta 1 (IL-12Rβ1) associated immunodeficiency in a previously healthy female who was initially misdiagnosed with sarcoidosis. M. genavense is a nontuberculous mycobacterium which can cause lymphadenopathy, gastrointestinal and bone marrow infiltration in immunocompromised patients. With this case report we aim to highlight that an infection with M. genavense on the ground of a genetic defect of mycobacterial immune control may represent a rare differential diagnosis of sarcoidosis.Case presentationA 31-year-old female was referred to our hospital with progressive lymphadenopathy, hepatosplenomegaly, pancytopenia and systemic inflammation. She had previously been evaluated for generalized lymphadenopathy in another hospital. At that time, lymph node biopsies had revealed sarcoid-like lesions and a systemic corticosteroid treatment was initiated based on a putative diagnosis of sarcoidosis. When her condition worsened, she was transferred to our university clinic, where the diagnosis of disseminated M. genavense infection owing to an inborn interferonopathy was made. Her family history revealed that her brother had also suffered from IL-12Rβ1 deficiency and had died from a systemic infection with M. genavense at the age of 21. The patient received antimycobacterial treatment combined with subcutaneous type I interferon, which eventually led to a gradual improvement over the next months.ConclusionsDifferentiating between sarcoidosis and sarcoid-like lesions secondary to infections may be challenging, especially when pathogens are difficult to detect or not expected in an apparently immunocompetent patient. Patients with IL-12Rβ1-associated immunodeficiency may be asymptomatic until adulthood, and disseminated M. genavense infection on the grounds of an IL-12Rβ1-associated immunodeficiency may represent a rare differential diagnosis of sarcoidosis.

Disseminated Mycobacterium genavense infection in a guinea pig (Cavia porcellus): a case report

BackgroundMycobacteria are found in many environmental conditions and infect a variety of species, including rodents and rabbits. Guinea pigs are used experimentally as a model for Mycobacterium tuberculosis, but natural mycobacteriosis in guinea pigs has not been reported.Case presentationA 1.5-year-old female guinea pig was found acutely deceased with no premonitory illness. On gross post-mortem examination, multifocal to coalescing, raised, firm, pale tan nodules with discrete, irregular margins were noted over the surfaces of all lung lobes. Histopathology revealed nodules composed of clustered foamy macrophages and multinucleated giant cells containing numerous bacterial rods. Similar bacteria-laden macrophages were noted within sections of the liver, heart, palpebral conjunctiva, duodenum, and cecum. Polymerase chain reaction was performed on tissues collected during post-mortem examination. The 16S rRNA gene product was sequenced and was identical to the Mycobacterium genavense type strain.ConclusionsTo the best of the author’s knowledge, this report details the first documented case of Mycobacterium genvaense infection in a guinea pig and a follow up investigation of close-contact animals. Given their experimental susceptibility and this clinical case report, mycobacteriosis should be considered as a differential in guinea pigs exhibiting weight loss in the absence of other clinical signs. With the potential for zoonotic transmission in immunosuppressed individuals, precautions should be taken to safeguard human health in cases of guinea pigs with suspected M. genavense infection.

Disseminated Mycobacterium genavense Infection in Patient with Adult-Onset Immunodeficiency

We report a case of disseminated Mycobacterium genavense infection resulting from neutralizing anti–interferon-γ autoantibodies in the patient. We identified M. genavense targeting the hsp65 gene in an aspiration specimen of the lymph node. Adult-onset immunodeficiency caused by neutralizing anti–interferon-γ autoantibodies, in addition to HIV infection, can lead to disseminated nontuberculous mycobacterial infection.

Disseminated Mycobacterium genavense in the immunocompromised: A Case Series at Mayo Clinic Rochester

Background Mycobacterium genavense can cause serious disease in the immunocompromised. We report our experience with this uncommon infection.MethodsRetrospective review of M. genavense infection at Mayo Clinic (2010–2017).ResultsThree patients were diagnosed with M. genavense from 2010 to 2017 (Table 1). Lymph node biopsy noted non-necrotizing granulomatous inflammation with AFB in 2 patients. Delayed growth in culture was noted after at least 6 weeks incubation. All patients were started on mycobacterial therapy; no isolate grew sufficiently for drug susceptibility testing.AgeGenderRisk factorPresentationMicrobiologyAntimicrobialsManagementOutcome51MRenal transplant Prednisone2 months right TKA painPositive right knee operative culture at 12 weekCiprofloxacin Ethambutol Rifampin ClarithromycinTKA resection + arthrodesis 24 mo antimicrobials9 y – no relapse66FAzathioprine Idiopathic CD4 lymphopeniaAbdominal pain, fever, weight lossIntra-abdominal lymphadenopathy (Figure 1 and 2)Positive mesenteric lymph node culture at 8 week, blood cultures at 6 weekClarithromycinMoxifloxacinRifabutinSymptoms resolvedExpired from stroke - 7 mo36FAIDSAbdominal painIntra-abdominal lymphadenopathyPositive mesenteric lymph node culture at 11 weekClarithromycin Rifabutin EthambutolSymptoms improved at 1 moLost to followupConclusion M. genavense is an environmental mycobacteria, it rarely causes infection in non-HIV hosts. Our cases involved advanced HIV, solid organ transplant and idiopathic CD4 lymphopenia. Presentation with GI and systemic symptoms is common, pulmonary and cutaneous less so. Growth in culture requires prolonged incubation (8–12 weeks) in broth media with Mycobactin J supplementation. Positive pathological examination for AFB organisms, negative probes for MTB or MAC combined with persistently negative cultures, should raise the suspicion for this organism in the right clinical setting. It is generally susceptible to rifamycins, fluoroquinolones and macrolides; resistant to isoniazid and sometimes pyrazinamide. Immunosuppression should be reduced if possible to speed recovery. Duration of therapy is usually at least 12 months for disseminated disease, depending on response and immunosuppression.Disclosures All authors: No reported disclosures.

Immune reconstitution inflammatory syndrome due to Mycobacterium genavense in an HIV-infected patient: Impact of rapid species identification by rpoB sequencing on clinical management

Introduction: Diagnosis of infections due to Mycobacterium tuberculosis has been recently facilitated with the worldwide implementation of rapid molecular tests. However, the diagnosis of non-TB mycobacteria (NTM) remains a major challenge for laboratories, as this group of bacteria contains over 150 different species with highly variable bacteriological properties. The development and implementation in clinical practice of techniques allowing rapid identification of NTM at the species level is, therefore, important for clinical laboratories. We report the case of an HIV-1 positive patient presenting with severe NTM infection who benefited from a novel rapid diagnostic technique, based on the direct sequencing of the rpoB gene from smear-positive clinical samples. Case Presentation: A 43-year-old HIV-1 positive woman was hospitalized for bicytopenia in the presence of an inflamed supraclavicular lymph node. The diagnosis of disseminated Mycobacterium genavense infection, which involved the bone marrow and several lymph nodes, was missed by conventional mycobacteriological techniques. Identification was obtained by performing direct sequencing of the rpoB gene. Conclusion: We describe a novel technique that allows the rapid diagnosis of NTM infections directly from biological samples. This technique is now implemented in our routine workflow for smear and culture-positive samples, after the exclusion of TB, by rapid molecular assays.

Disseminated Mycobacterium genavense infection in a patient with immunosuppressive therapy and lymphoproliferative malignancy

We present the case of a 51-year-old woman who presented a right supraclavicular mass corresponding to lymphadenitis with atypical mycobacterium (Mycobacterium genavense). Later, she developed subcutaneous purulent small nodules containing the same germ. The presence of this mycobacterium was in the context of recurrent peripheral T-cell lymphoma and immunosuppressive therapy for seronegative inflammatory polyarthritis.

Disseminated Mycobacterium genavense infection after immunosuppressive therapy shows underlying new composite heterozygous mutations of β1 subunit of IL-12 receptor gene

Disseminated Mycobacterium genavense infection after immunosuppressive therapy shows underlying new composite heterozygous mutations of β1 subunit of IL-12 receptor gene

Disseminated Mycobacterium genavense infection in a patient with a novel partial interleukin-12/23 receptor β1 deficiency

A patient presented with late onset disseminated nontuberculous mycobacterium (NTM) infection due to a novel interleukin-12/interleukin-23 receptor β1 (IL-12/IL-23Rβ1) mutation, r.1561C>G, leading to the amino acid substitution R521G. This is the second patient reported with a partial IL-12/IL-23Rβ1 defect.

GI involvement in disseminated Mycobacterium genavense: endoscopy and histology

1A 34-year-old man ultimately shown to have immunodeficiency and disseminated Mycobacterium genavense associated with protein-losing enteropathy presented with cachexia and generalized weakness. Physical examination revealed a cachectic man with generalized muscle wasting and a protuberant abdomen with shifting dullness, but without tenderness, rebound, or guarding. Laboratory data showed the following: white blood cell count, 4.8 K/µL (normal range 3.98–10.14 K/µL); hemoglobin, 13.6 g/dL (normal range 11.2–15.7 g/dL); platelet count, 73,000/µL (normal range 173–369 K/µL); sodium, 134 mmol/L (normal range 135–144 mmol/L); potassium, 3.7 mmol/L (3.3–5.1 mmol/L); urea nitrogen, 25 mg/dL (normal range 8–22 mg/dL); creatinine, 0.86 mg/dL (normal range 0.56–1.16 mg/dL); alkaline phosphatase, 153 U/L (normal range 37–116 IU/L); alanine aminotransferase, 84 U/L (normal range 6–41 U/L); aspartate aminotransferase, 120 U/L (normal range 9–34 U/L); total protein, 3.9 g/dL (normal range 6.4 – 8.2 g/dL); albumin, 1.4 g/dL (normal range 2.5–4.8 g/dL); preal-bumin, 15 mg/dL (normal range 17–39 mg/dL); 24-hour stool a1- antitrypsin level, 93 mg/dL (normal <54 mg/ dL); trace urinary protein; negative HIV test results; IgG, 377 mg/dL (normal range 642–1730 mg/dL); IgA, 20 mg/dL (normal range, 91–499 mg/dL); IgM, less than 21 mg/dL (normal 34–342 mg/dL); and IgE, 2.4 mg/dL (normal range 0–90.0 IU/mL). CT scan of the abdomen and pelvis revealed nonspecific small-bowel thickening, sigmoid mucosal enhancement, and extensive mesenteric adenopathy (A). EGD revealed diffuse esophageal mucosal denudation and friability, mild thickening of the gastric and duodenal folds (B). Colonoscopy (C) showed mucosal edema, absence of vasculature, and loss of haustral folds. Biopsy specimens (D,E) revealed expansion of the lamina propria, which was filled with foamy macrophages that contained acid-filled bacilli, subsequently shown to be M genavense.

Delayed Diagnosis of Disseminated Mycobacterium genavense Infection in a Human Immunodeficiency Virus-Negative Young Woman

Delayed Diagnosis of Disseminated Mycobacterium genavense Infection in a Human Immunodeficiency Virus-Negative Young Woman

Disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient: case report and review of the literature

We report a case of disseminated Mycobacterium genavense with pulmonary nodules in a kidney transplant recipient and review the associated literature. Disease caused by M. genavense has been recognized in acquired immunodeficiency syndrome (AIDS) patients since 1990, with subsequent case reports in other immunocompromised host populations. In AIDS patients, pulmonary lesions are an uncommon finding. This is the first report to our knowledge of a human immunodeficiency virus (HIV)-negative patient with pulmonary nodules as a feature of disseminated M. genavense. Diagnosis of M. genavense is often challenging and frequently requires nucleic acid-based identification techniques. Because of limitations in culture and drug susceptibility testing, treatment regimens rely on reported clinical experience. This case report and literature review illustrates a successful approach to the diagnosis and treatment of disseminated M. genavense and summarizes the reports of M. genavense infection in HIV-negative patients.

Disseminated Mycobacterium genavense infection in a healthy boy

Mycobacterium genavense (M genavense) has been recognized as a life-threatening pathogen in severely immunocompromised patients. To our knowledge, disseminated M genavense infection has never been described in immunocompetent individuals. Here, we report a case of disseminated M genavense infection in a healthy Japanese boy. A 15-year-old boy who had never been diagnosed with an immunodeficiency disorder was hospitalized because of ileus. Tumorous lesions were identified in the ileum, cecum, and ascending colon, resulting in stenosis of ileocecal valve. There was diffuse proliferation of histiocytes throughout the intestinal wall, along with lymphocytic infiltration. No nuclear or cellular atypia was present in these cells. Ziehl-Neelsen staining revealed numerous acid-fast bacteria in histiocytes. After surgery, systemic lymph node swelling was noticed by generalized examination, including the mesenteric and cervical lymph nodes. M genavense DNA was identified by direct sequencing of 16S ribosomal DNA that had been amplified by polymerase chain reaction.

Intestinal involvement by Micobacterium genavense in an immunodepressed patient

Mycobacterium genavense is a nontuberculous mycobacteria that has recently been described as a cause of human pathology. 1 Casal M.M. Casal M. Atypical mycobacteria as emerging pathogens. Enf Emerg. 2000; 2 ([Spanish]): 220-230 Google Scholar This intestinal affectation causes alterations in the mucosa that make diagnosis difficult. By means of endoscopy, it is possible to detect edematous folds, loss of elasticity, and increased friability of the mucosa. It usually affects severely immunodepressed patients (CD4 <100 cells/mm3), causing up to 13% of all nontuberculous mycobacteria infections in patients with AIDS. 2 de Lastours V. Guillemain R. Mainardi J.L. et al. Early diagnosis of disseminated Mycobacterium genavense infection. Emerg Infect Dis. 2008; 14: 346-347 PubMed Google Scholar The organs most commonly affected are the small bowel, bone marrow, spleen, liver, and lymph nodes. 3 Bogdan C. Kern P. Richter E. et al. Systemic infection with Mycobacterium genavense following immunosuppressive therapy in a patient who was seronegative for human immunodeficiency virus. Clin Infect Dis. 1997; 24: 1245-1247 Crossref PubMed Scopus (29) Google Scholar This strain of bacteria can be treated by prescribing rifampicin and streptomycin and is resistant to isoniazide. 4 Shrestha Y. Ortega W. Nancy P. Matuschak G. Mycobacterium genavense: a rare pulmonary pathogen in a patient with advanced AIDS. Chest. 2006; 130: 321S Google Scholar

Early Diagnosis of Disseminated Mycobacterium genavense Infection

To the Editor: Nontuberculous mycobacteria are environmental organisms that cause life-threatening diseases, particularly in immunocompromised hosts. They are increasingly recognized for causing problems in the management of solid-organ transplant recipients, due to improved diagnostic methods as well as increasing numbers and life expectancy of these patients (1). The slow-growing Mycobacterium genavense is a ubiquitous nontuberculous mycobacterium; it is reportedly isolated from tap water, pets, and the gastrointestinal tract of healthy humans (1,2). It was first recognized as a human pathogen in a patient with AIDS but has not yet been found in heart transplant recipients (3). We report early diagnosis of disseminated M. genavense infection in a heart transplant recipient. A 37-year-old man was hospitalized in September 2001 for abdominal pain, sweats, and weight loss; he had received a heart transplant 3 years earlier. Immunosuppressive treatment, which began immediately after transplantation, consisted of tacrolimus (5 mg) and mycophenolate mofetil (2 g) daily; concurrent steroid therapy was tapered off over the next 6 months. A computed tomographic (CT) scan showed numerous large lymph nodes in his abdomen (Figure). Endoscopic examinations showed diffuse inflammation of the mucosa of the duodenum, ileum, and colon. Multiple biopsy samples were submitted for histologic analysis, culture, and molecular biological analysis. Immediate 16S rRNA gene amplification that used universal primers (4) and sequencing of samples taken directly from the biopsy material led to the identification of M. genavense. A 475-bp fragment was sequenced, and 99% homology with the gene of type strain ATCC 51234 (GenBank accession no. {type:entrez-nucleotide,attrs:{text:X60070,term_id:44288}}X60070) was found. PCR results were positive for 2 of the 4 samples tested. The molecular identification was compatible with the subsequent histologic finding of profound macrophage infiltration without granuloma and the presence of Ziehl-Neelsen–positive bacilli. Five weeks later, the molecular diagnosis was confirmed by blood cultures and cultures of the intestinal mucosa samples (Inno-LiPA Mycobacteria test, version 2, Innogenetics, Courtaboeuf, France). The direct molecular diagnosis of M. genavense enabled immediate treatment of the patient with the combination of moxifloxacin, ethambutol, clarithromycin, and amikacin; mycophenolate mofetil was discontinued. Clofazimine was added to the treatment regimen 3 months later, when a control CT scan showed that some of the enlarged mesenteric lymph nodes had increased further. After 5 months, the clinical signs resolved, and after 9 months, the lymph nodes were substantially smaller. CT scan results were within normal limits after 12 months of treatment; only ethambutol and clarithromycin were continued for an additional 6 months. There was no sign of M. genavense infection relapse 3 years after the diagnosis had been made. Figure Initial computed tomographic scan of the abdomen, performed after intravenous injection of contrast dye, showing numerous enlarged para-aortic lymph nodes (arrow). Nontuberculous mycobacteria in persons who have received heart or other solid-organ transplants remain a rare cause of late infectious complications and occur ≈3.5 years after transplantation (1,4). In the subgroup of heart transplant recipients, skin disease is the most common clinical manifestation, followed by pulmonary and disseminated disease; M. kansasii, M. avium complex, and M. haemophilum infections are most frequently encountered (1,5). M. genavense causes up to 12.8% of all nontuberculous mycobacteria infections in AIDS patients; these infections are clinically similar to those caused by the M. avium complex (1,6). M. genavense infections occur only rarely in persons other than AIDS patients (as in the present case), but they always occur in immunocompromised persons (7,8). To date, only 1 case of disseminated infection has been reported in a solid-organ (kidney) transplant recipient; the diagnosis was made by molecular identification in isolates from blood and marrow cultures. That patient died of complications from M. genavense infection (9). Because M. genavense is a fastidious organism, the infections it causes are difficult to diagnose and their frequency is probably underestimated, which may change with increased use of direct molecular biological methods. Optimal treatment of M. genavense infections has not been established (10). Experience with M. genavense infections in AIDS patients and with other nontuberculous mycobacteria infections in solid-organ transplant recipients suggests that at least 2 antimicrobial drugs should be used for a prolonged period; when possible, immunosuppressive drugs should be concurrently reduced (1,3,6,10). Outcome of nontuberculous mycobacteria infections in transplant patients is highly variable (1,5) but was satisfactory in the present patient, who was treated with quintuple antimicrobial-drug therapy and reduced immunosuppressive therapy. This case of a disseminated infection due to M. genavense in a heart transplant recipient was diagnosed early. Universal 16S rRNA gene sequencing after amplification directly from intestinal biopsy specimens enabled fast diagnosis and appropriate management.

Disseminated Mycobacterium genavense infection in a FIV-positive cat

An 8-year-old FIV-positive Australian cat was presented with coughing, periocular alopecia, pyrexia and inappetence. Skin scrapings demonstrated Demodex cati mites. Antibiotics were administered and it was treated successfully for periocular demodectic mange, but the cat continued to exhibit respiratory signs and lose weight. Further investigation revealed an ascarid infection and active chronic inflammation of undetected cause affecting the lower airways. Repetitive treatment with pyrantel failed to eradicate the ascarid infection. The cat became cachectic and developed moist ulcerative dermatitis of the neck, severe non-regenerative anaemia, leucopenia and thrombocytopenia. Necropsy and histopathology revealed mycobacteriosis affecting skin, lungs, spleen, lymph nodes, liver and kidney. Attempted culture of frozen tissues at a mycobacteria reference laboratory was unsuccessful. Paraffin-embedded, formalin-fixed tissue was retrieved and examined using PCR to amplify part of the 16S rRNA gene. A diagnosis of disseminated Mycobacterium genavense infection was made based on the presence of acid fast bacteria in many tissues and partial sequence of the 16S rRNA gene. Although M genavense has been identified previously as a cause of disseminated disease in AIDS patients, this is the first report of infection in a cat. It was suspected that the demodecosis, recurrent ascarid infections and disseminated M genavense infection resulted from an immune deficiency syndrome consequent to longstanding FIV infection.

Treatment of disseminated Mycobacterium genavense infection in a murine model with ciprofloxacin, amikacin, ethambutol, clarithromycin and rifabutin.

Mycobacterium genavense is a recently described agent which can induce disseminated infections in patients with AIDS. Up to now, no standard approach to treatment has been defined and patients have been treated empirically with antibiotics used for treating infections caused by other nontuberculous mycobacteria. In this study, we compared the effectiveness of ciprofloxacin, amikacin, ethambutol, clarithromycin and rifabutin in the treatment of an animal model of M. genavense infection in C57BL/6 mice. Antimycobacterial treatment was started 4 weeks after an intravenous bacterial challenge and was continued for 30 days. Treated and control mice were killed at days 15 and 30 of treatment and the number of viable bacteria in their spleens was counted. Treatment with clarithromycin (50 mg/kg/day sc) and rifabutin (20 mg/kg/day po) was found to decrease the bacterial counts in the spleens significantly as early as 15 days after the onset of treatment (P < 0.01). The effect of treatment was more pronounced after 30 days of treatment (P < 0.001). Amikacin (25 mg/kg/day sc) and ethambutol (50 mg/kg/day sc) were found to decrease significantly the cfu in the spleens only after 30 days of treatment (P < 0.01). Ciprofloxacin (25 mg/kg/day sc) was ineffective in the experimental conditions used here.

Treatment of disseminated Mycobacterium genavense infection

Treatment of disseminated Mycobacterium genavense infection

Disseminated Mycobacterium genavense infection in Canadian AIDS patients

Mycobacterium genavense is a recently described mycobacterial species which thus far has been identified only in persons with advanced HIV disease. It appears to be a rare pathogen with an undefined reservoir. We describe the first two cases of M. genavense infection in Canadian AIDS patients. The clinical presentation of fever and wasting with extremely low CD4 lymphocyte counts was indistinguishable from disseminated M. avium complex (MAC) infection. However, blood cultures in BACTEC 13A medium required a mean of 58 days (range 41–87) to detect growth of M. genavense in contrast to a mean of 10 days for MAC in our laboratory. M. genavense infection is underdiagnosed due to the lack of universal use of BACTEC liquid medium and the use of relatively short incubation times (only 6 weeks) by some laboratories. The value of antimycobacterial therapy for M. genavense is unknown, but anecdotal data suggest that treatment with a regimen appropriate for MAC may be beneficial.