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Mycobacteria other than those of the M. tuberculosis complex and M. leprae are referred to as nontuberculous or atypical mycobacteria and are ubiquitous in soil and water.

Microbiology !!navigator!!

NTM are broadly differentiated into rapidly and slowly growing forms (<7 days and 7 days, respectively). M. abscessus, M. fortuitum, and M. chelonae are examples of rapid growers; species such as M. avium and M. intracellulare (the M. avium complex, or MAC), M. kansasii, M. ulcerans, and M. marinum are slow growers.

Epidemiology !!navigator!!

Most NTM cause disease in humans only rarely unless some aspect of host defense is impaired (as in bronchiectasis) or breached (as by inoculation-e.g., during liposuction or trauma). The bulk of NTM disease in North America is due to M. kansasii, MAC organisms, and M. abscessus.

Clinical Manifestations !!navigator!!

Although there are many NTM species, the clinical presentations they cause can be broadly categorized by the organ system(s) affected.

  • Disseminated disease is now quite rare; even pts with advanced HIV infection do not often develop disseminated NTM infection, given improved treatment of HIV infection and effective antimycobacterial prophylaxis.
    • Organisms typically spread from the bowel to the bone marrow and bloodstream, but disease is indolent, and it can take weeks or months for the pt to present for medical attention with malaise, fever, weight loss, organomegaly, and lymphadenopathy.
    • A child with involvement of two or more organ systems and no iatrogenic cause should be evaluated for defects in the interferon γ;/interleukin 12 pathway.
  • Pulmonary disease represents the most common NTM infection in industrialized countries. MAC organisms are most commonly involved in North America. Pts present with months or years of throat clearing, nagging cough, and slowly progressive fatigue. M. kansasii can cause a TB-like syndrome, with hemoptysis, chest pain, and cavitary lung disease.
  • Isolated cervical lymphadenopathy is the most common NTM infection among young children in North America and is most frequently caused by MAC organisms. The nodes are typically firm and painless and develop in the absence of systemic symptoms.
  • Skin and soft-tissue disease usually requires a break in the skin for introduction of the organism. Different NTM species are associated with specific exposures.
    • M. fortuitum is linked to pedicure bath-associated infections, particularly if skin abrasion (e.g., during leg shaving) has immediately preceded the pedicure.
    • Rapidly growing NTM are associated with outbreaks of infection acquired via skin contamination from surgical instruments (especially in cosmetic surgery), injections, and other procedures. These infections are typically accompanied by painful, erythematous, draining SC nodules, usually without associated fever or systemic symptoms.
    • M. marinum can be acquired from fish tanks, swimming pools, barnacles, and fish scales. Pts typically develop papules or ulcers (“fish-tank granuloma”) that can progress to tendonitis and tender nodules on the arm in a pattern similar to that caused by Sporothrix schenckii. Lesions appear days or weeks after acquisition of the organism.
    • M. ulcerans is a waterborne organism found primarily in tropical areas, especially in Africa. Skin lesions are typically painless, clean ulcers that slough and can cause osteomyelitis.

Diagnosis !!navigator!!

Similar to M. tuberculosis, NTM can be detected on acid-fast or fluorochrome smears of clinical samples and can be cultured on mycobacterial medium. Isolation of NTM from a clinical specimen may reflect colonization and requires an assessment of the organism's clinical significance.

  • Isolation of NTM from blood specimens is clear evidence of disease; many NTM species require special media and will not grow in standard blood culture medium.
  • The American Thoracic Society has published guidelines for the diagnosis of pulmonary NTM disease that require the growth of NTM from two of three sputum samples, a positive bronchoalveolar lavage sample, or a pulmonary parenchyma biopsy sample with granulomatous inflammation or mycobacteria found on section and NTM in culture. Although these guidelines are specific to MAC, M. abscessus, and M. kansasii, they probably apply to other NTM as well.
  • The only antibiotic susceptibility assessment indicated is testing of MAC organisms for susceptibility to clarithromycin and of M. kansasii for susceptibility to rifampin.
TREATMENT

Infections with NTM

Since NTM disease evolves over a long period, it is rarely necessary to begin treatment on an emergency basis before identifying the infecting species.

  • MAC infection requires multidrug therapy with a macrolide (clarithromycin or azithromycin), ethambutol, and a rifamycin (rifampin or rifabutin). Therapy is prolonged, generally continuing for 12 months after culture conversion; typically, a course lasts for at least 18 months.
  • M. kansasii lung disease is similar to TB in many ways and is also effectively treated with isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg per day). Treatment should continue until cultures have been negative for at least 1 year.
  • Extrapulmonary disease due to rapidly growing NTM is often treated successfully with a macrolide and another drug (with the choice based on in vitro susceptibility). Pulmonary disease due to M. abscessus is difficult to cure and often requires repeated courses that include a macrolide along with an IV-administered agent such as amikacin, a carbapenem, cefoxitin, or tigecycline.
  • M. marinum infection is effectively treated with any combination of a macrolide, ethambutol, and a rifamycin for 1-2 months after clinical resolution of isolated soft-tissue disease; tendon and bone involvement may require longer courses in light of clinical evolution.
  • Treatment of infections caused by other NTM is less well defined, but macrolides and aminoglycosides are usually effective, with other agents added as indicated.

Outline

Section 7. Infectious Diseases