Disseminated Mycobacterium genavense infection in an immunocompetent adult: a case report
Authors: G. Cornelis, M. Reynders, J. Deprez, A. Vankeerberghen, H. Orlent
Journal: Clinical Microbiology and Infection (2018)

A 79-year-old man was admitted to our hospital because of persistent episodic fever and weight loss of 12 kg after 3 months. About 13 weeks before, he underwent a percutaneous transluminal angioplasty (PTA) of both femoral arteries. Physical examination was unremarkable. Laboratory tests showed mild inflammation (C-reactive protein 46 mg/L) and elevated liver enzymes (gamma-glutamyl transferase, 470 U/L; alkaline phosphatase, 815 U/L; aspartate aminotransferase, 69 U/L; alanine aminotransferase, 51 U/L), with a normal bilirubin. A computed tomography (CT) scan of the abdomen revealed a saccular aneurysm of the abdominal aorta. Thirty-five sets of paired blood cultures remained negative. A liver core needle biopsy showed granulomatous hepatitis. Liver tissue culture and workup for viral aetiologies of granulomatous hepatitis remained negative. Subsequently, a positron emission tomography (PET)-CT study revealed a hot spot in the infrarenal aorta. This infected aneurysm was resected with insertion of a tube prosthesis. Acid-fast bacilli were visible on an auramine-rhodamine stain, although a prolonged bacterial, mycobacterial, and mycological culture of the resection piece remained negative. DNA extraction from the resection tissue was performed using the UMD Universal kit (Molzym GmbH & co., Bremen, Germany). The recovered nucleic acid extract underwent an in-house “panmycobacterial” nested polymerase chain reaction (PCR) that was an adaptation of the protocol described by De Baere et al. [[1]De Baere T. de Mendonça R. Claeys G. Verschraegen G. Mijs W. Verhelst R. et al.Evaluation of amplified rDNA restriction analysis (ARDRA) for the identification of cultured mycobacteria in a diagnostic laboratory.BMC Microbiol. 2002; 1: 4Crossref Scopus (29) Google Scholar], followed by universal 16S rRNA sequencing. A 486-bp fragment was sequenced and 100% homology with all Mycobacterium genavense 16S sequences present in Genbank was found (GenBank accession no. X60070). As M. genavense is a known pathogen in severe immunocompromised patients, studies on the immune status of our patient were performed. HIV serology was negative. Serum protein electrophoresis with levels of immunoglobulins (IgG, IgA, IgM) and flow cytometric analysis of lymphoid cells (CD4, CD8, and CD20 lymphocyte subtypes) all appeared normal. Combined antimycobacterial treatment (moxifloxacin, rifampicin, and clarithromycin) was initiated, with resolution of fever and biochemical abnormalities. A PET scan after 6 months showed no residual aortic hot spot. A 9-month treatment period was maintained and recently stopped. Follow-up so far showed no signs of infection. In 1990 Hirshel et al. [[5]Hirschel B. Chang H.R. Mach N. Piguet P.F. Cox J. Piguet J.D. et al.Fatal infection with a novel, unidentified Mycobacterium in a man with the acquired immunodeficiency syndrome.N Engl J Med. 1990; 323: 109-113Crossref PubMed Scopus (90) Google Scholar] described a fatal infection characterized by fever and massive weight loss, caused by an unidentified mycobacterium. This novel mycobacterium, M. genavense, was only identified in 1992 as a pathogen responsible for disseminated infection in HIV-infected patients [[2]Santos M. Gil-Brusola A. Escandell A. Blanes M. Gobernado M. Mycobacterium genavense infections in a tertiary hospital and reviewed cases in non-HIV Patients.Patholog Res Int. 2014; 2014: 1-8Crossref Scopus (22) Google Scholar]. It has been identified in more than 10% of disseminated non-tuberculous mycobacterial infections in HIV-infected patients [[2]Santos M. Gil-Brusola A. Escandell A. Blanes M. Gobernado M. Mycobacterium genavense infections in a tertiary hospital and reviewed cases in non-HIV Patients.Patholog Res Int. 2014; 2014: 1-8Crossref Scopus (22) Google Scholar]. Disease is characterized by fever, diarrhoea, and weight loss [[3]Ombelet S. Van Wijngaerden E. Lagrou K. Tousseyn T. Gheysens O. Droogne W. et al.Mycobacterium genavense infection in a solid organ recipient: a diagnostic and therapeutic challenge.Transpl Infect Dis. 2016; 18: 125-131Crossref PubMed Scopus (11) Google Scholar]. The clinical presentation is similar to that of Mycobacterium avium, though gastrointestinal symptoms such as abdominal pain and diarrhoea are more prominent, presumably due to a natural reservoir of the mycobacterium in the intestine [[2]Santos M. Gil-Brusola A. Escandell A. Blanes M. Gobernado M. Mycobacterium genavense infections in a tertiary hospital and reviewed cases in non-HIV Patients.Patholog Res Int. 2014; 2014: 1-8Crossref Scopus (22) Google Scholar]. There seems to be a reservoir in tap water and in the gastrointestinal tract of animals and immunocompetent humans, suggesting a ubiquitous distribution of this mycobacterium [2Santos M. Gil-Brusola A. Escandell A. Blanes M. Gobernado M. Mycobacterium genavense infections in a tertiary hospital and reviewed cases in non-HIV Patients.Patholog Res Int. 2014; 2014: 1-8Crossref Scopus (22) Google Scholar, 3Ombelet S. Van Wijngaerden E. Lagrou K. Tousseyn T. Gheysens O. Droogne W. et al.Mycobacterium genavense infection in a solid organ recipient: a diagnostic and therapeutic challenge.Transpl Infect Dis. 2016; 18: 125-131Crossref PubMed Scopus (11) Google Scholar]. In this specific case, we suspect a relationship with the PTA as the infection included a mycotic aneurysm, though this relationship was not previously described. The diagnosis of M. genavense infection is challenging as this pathogen has a fastidious growth in liquid media and it does not grow at all on standard solid media. Primary cultures for isolation require liquid broth media such as BACTEC 12B medium or Middlebrook 7H9 medium in which these Mycobacteria grow to limited extent within 3–12 weeks [[3]Ombelet S. Van Wijngaerden E. Lagrou K. Tousseyn T. Gheysens O. Droogne W. et al.Mycobacterium genavense infection in a solid organ recipient: a diagnostic and therapeutic challenge.Transpl Infect Dis. 2016; 18: 125-131Crossref PubMed Scopus (11) Google Scholar]. Hence its rapid identification relies on molecular biological techniques, using a species-specific M. genavense PCR [2Santos M. Gil-Brusola A. Escandell A. Blanes M. Gobernado M. Mycobacterium genavense infections in a tertiary hospital and reviewed cases in non-HIV Patients.Patholog Res Int. 2014; 2014: 1-8Crossref Scopus (22) Google Scholar, 3Ombelet S. Van Wijngaerden E. Lagrou K. Tousseyn T. Gheysens O. Droogne W. et al.Mycobacterium genavense infection in a solid organ recipient: a diagnostic and therapeutic challenge.Transpl Infect Dis. 2016; 18: 125-131Crossref PubMed Scopus (11) Google Scholar]. Under-reporting of M. genavense infections is likely because of the difficult identification of this mycobacteria. The vast majority of cases have been described among AIDS patients with a CD4 count below 50/mm3, but disseminated infection is increasingly reported among transplant recipients and patients with other causes of immunosuppression [[2]Santos M. Gil-Brusola A. Escandell A. Blanes M. Gobernado M. Mycobacterium genavense infections in a tertiary hospital and reviewed cases in non-HIV Patients.Patholog Res Int. 2014; 2014: 1-8Crossref Scopus (22) Google Scholar]. There are only two cases described in immunocompetent hosts. These were both children, one of them with a disseminated disease [[4]Miyoshi H. Tamura G. Satoh T. Homma R. Omoto E. Nakano N. et al.Disseminated Mycobacterium genavense infection in a healthy boy.Hum Pathol. 2010; 41: 1646-1649Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar]. There is still insufficient data on optimal treatment. Therapeutic regimes should always include at least two antimycobacterial drugs, preferably clarithromycin and ethambutol, with sometimes addition of rifabutin and amikacin [[3]Ombelet S. Van Wijngaerden E. Lagrou K. Tousseyn T. Gheysens O. Droogne W. et al.Mycobacterium genavense infection in a solid organ recipient: a diagnostic and therapeutic challenge.Transpl Infect Dis. 2016; 18: 125-131Crossref PubMed Scopus (11) Google Scholar]. The authors have no conflict of interests to be declared. No external funding was received.