Nontuberculous Mycobacteria Infections in Immunosuppressed Hosts

https://doi.org/10.1016/j.ccm.2014.11.002Get rights and content

Section snippets

Key points

  • Nontuberculous mycobacteria (NTM) disease is an important cause of disease in immunosuppressed hosts.

  • Mycobacterium avium complex is the leading cause of NTM disease in immunosuppressed patients, but rapid growers including Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, and a variety of rare species are also important.

  • In immunosuppressed patients, about half of NTM disease is pulmonary and the remainder is split between skin/soft tissue and disseminated.

  • Treatment is

Disease description

NTM disease is increasing in the United States. Prevots and colleagues11 used data from several large health maintenance organizations in the western United States and found an increase of 2.6% per year from 1994 to 2006. The first incidence estimate of NTM disease is 5.7 per 100,000 in Oregon in 2012, with rates 3 to 4 times higher in individuals older than 70 years.14 Most of this is pulmonary disease whereby a large proportion occurs outside of recognized settings of immunosuppression. For

Epidemiology

The epidemic of disseminated MAC infection began in 1982 with a sharp increase in the number of cases associated with the AIDS epidemic.3 Up to 24% of AIDS patients had disseminated MAC by 1989/1990.2 Distinguishing it from other opportunistic infections that occurred earlier in the course of HIV infection, disseminated MAC was associated with very low CD4+ counts, generally fewer than 50 cells/mm3.2, 3 The introduction of HAART in 1997 led to a sharp decline in the number of disseminated MAC

Corticosteroids

Oral and inhaled corticosteroids are routinely prescribed to suppress inflammation in several chronic conditions, including chronic obstructive pulmonary disease (COPD), asthma, and rheumatoid arthritis. Corticosteroids are known to increase the risk of pneumonia in patients with COPD and tuberculosis as much as 5-fold,33 while the relative risks of NTM are likely even greater. Oral prednisone use was 8 times higher among NTM cases than in controls in a case-control study in Oregon and

Solid organ transplants

Solid organ transplant recipients take a variety of immunosuppressive medications after transplantation. The most common maintenance drugs include calcineurin inhibitors (tacrolimus and cyclosporine), mammalian target of rapamycin (mTOR) inhibitor (sirolimus), prednisone, and others depending on the organ being transplanted. All data on NTM in transplants is found in case reports and institutional case series. To the authors’ knowledge there are no population-based prevalence or incidence

Solid tumors and hematologic malignancies

Patients with cancer are at higher risk for NTM disease. Underlying cellular immunity impairment and immunosuppression from antineoplastic chemotherapy also contribute to the increased risk.1, 8, 55 Patients with lung tumors are at increased risk of pulmonary NTM infection probably because of localized airway destruction or damage, and hematologic malignancies put patients at higher risk of both localized infections near the site of catheter placement and disseminated infections. Hairy cell

Hematopoietic stem cell transplants

Hematopoietic stem cell transplants (HSCTs) are used to treat several hematologic malignancies, including leukemia, multiple myeloma, and others. The number of HSCTs has increased dramatically from 200 in 1980 to 20,000 in 2010.57 The risks of NTM are higher before the transplant, owing to underlying immune cell abnormalities, and during the phase of immune reconstitution that follows induction immunosuppression and the HSCT. HSCTs are most frequently associated with catheter and blood

Primary immunodeficiency diseases

Primary immunodeficiency diseases include a large number of conditions associated with defects in antibody responses, and cellular and innate immunity.63 A subset of these is associated with a documented or theoretic risk, and most are associated with the IL-12/IFN-γ axis.63, 64 Other conditions predisposing to NTM include chronic granulomatous disease, common variable immune deficiency, and hypogammaglobulinemia.63 A recent study of conditions associated with death from NTM found that primary

Summary

Diseases and therapies that reduce cell-mediated immunity increase the risk of NTM disease. The broadening use of immunosuppressive drugs including anti-TNF biologics in the United States, and the expanding practice of stem cell and solid organ transplantation, places an increasing number of patients at risk for NTM disease.38 With the exception of population-based studies of anti-TNF biologics and corticosteroids that report the risk of NTM at 8 to 50 times that of the general population, to

First page preview

First page preview
Click to open first page preview

References (64)

  • J.A. Havlik et al.

    Disseminated Mycobacterium avium complex infection: clinical identification and epidemiologic trends

    J Infect Dis

    (1992)
  • C.R. Horsburgh

    Mycobacterium avium complex infection in the acquired immunodeficiency syndrome

    N Engl J Med

    (1991)
  • I.H. Lichtenstein et al.

    Mycobacterial infections in renal transplant recipients: report of five cases and review of the literature

    Rev Infect Dis

    (1983)
  • J. Lloveras et al.

    Mycobacterial infections in renal transplant recipients. Seven cases and a review of the literature

    Arch Intern Med

    (1982)
  • R.A. Weinstein et al.

    Hairy cell leukemia: association with disseminated atypical mycobacterial infection

    Cancer

    (1981)
  • P.M. Cassidy et al.

    Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology

    Clin Infect Dis

    (2009)
  • T.K. Marras et al.

    Isolation prevalence of pulmonary non-tuberculous mycobacteria in Ontario, 1997 2003

    Thorax

    (2007)
  • D.R. Prevots et al.

    Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems

    Am J Respir Crit Care Med

    (2010)
  • K.L. Winthrop et al.

    Pulmonary disease associated with nontuberculous mycobacteria, Oregon, USA

    Emerg Infect Dis

    (2011)
  • C. Andrejak et al.

    Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis

    Thorax

    (2013)
  • E. Henkle et al.

    Incidence of nontuberculous mycobacterium disease in Oregon, 2007-2012

    (2014)
  • K.L. Winthrop et al.

    Mycobacterial diseases and antitumour necrosis factor therapy in USA

    Ann Rheum Dis

    (2013)
  • M. Mirsaeidi et al.

    Nontuberculous mycobacterial disease mortality in the United States, 1999-2010: a population-based comparative study

    PLoS One

    (2014)
  • S. Ehlers

    Role of tumour necrosis factor (TNF) in host defence against tuberculosis: implications for immunotherapies targeting TNF

    Ann Rheum Dis

    (2003)
  • T. Doherty et al.

    Mycobacterium haemophilum as the initial presentation of a B-cell lymphoma in a liver transplant patient

    Case Rep Rheumatol

    (2014)
  • K. Ducharlet et al.

    Recurrent Mycobacterium haemophilum in a renal transplant recipient

    Nephrology

    (2014)
  • E. Lhuillier et al.

    Relapsing Mycobacterium genavense infection as a cause of late death in a lung transplant recipient: case report and review of the literature

    Exp Clin Transplant

    (2012)
  • K.L. Winthrop et al.

    Association between the initiation of anti-antitumor necrosis factor therapy and the risk of herpes zoster

    JAMA

    (2013)
  • D.E. Griffith et al.

    An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases

    Am J Respir Crit Care Med

    (2007)
  • G. El Helou et al.

    Management of rapidly growing mycobacterial bacteremia in cancer patients

    Clin Infect Dis

    (2013)
  • K.L. Winthrop et al.

    Emerg Infect Dis

    Emerg Infect Dis

    (2009)
  • J.E. Kaplan et al.

    Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy

    Clin Infect Dis

    (2000)
  • Cited by (213)

    View all citing articles on Scopus

    Disclosures: None.

    View full text