nontuberculous%20mycobacterial%20disease
NONTUBERCULOUS MYCOBACTERIAL DISEASE
Nontuberculous mycobacteria are ubiquitous and are usually found in soil, natural and treated water sources. They are relatively uncommon cause of pulmonary disease and likely to cause disseminated disease.
May cause both asymptomatic infection and symptomatic disease in humans.
There is no evidence of animal-to-human or human-to-human transmission in immunocompetent hosts.
Nontuberculous mycobacterial pulmonary disease is a generally slowly progressive infection.
Signs and symptoms are generally nonspecific.

Diagnosis

Hypersensitivity-like Disease

  • Nontuberculous mycobacterial (NTM) pulmonary disease syndrome presenting like a hypersensitivity lung disease
  • One form of this syndrome is the “hot tub lung” which is associated w/ MAC exposure
  • Another form of this syndrome similar to hypersensitivity-like pneumonitis is associated w/ occupational exposures to metalworking fluids
    • Similar to “hot tub lung” but solely caused by M immunogenum

Evaluation

The following are criteria used to diagnose NTM Pulmonary Disease:

Clinical, radiographic & microbiologic criteria must all be met

Clinical

  • Signs & symptoms consistent w/ nontuberculous mycobacterium (NTM) pulmonary disease, &
  • Appropriate exclusion of other diagnoses (eg pulmonary TB, cancer)

Radiographic

  • Nodular or cavitary opacities on chest radiograph, or
  • In the absence of cavitations, high-resolution computed tomography (HRCT) scan that shows multifocal bronchiectasis & multiple small (noncalcified) nodules

Microbiologic

  • ≥2 positive culture results from separate expectorated sputum samples, or
  • ≥1 positive culture bronchial wash or lavage, or
  • Transbronchial or other lung biopsy w/ mycobacterial histopathologic features (granulomatous formation or acid-fast stain) & positive culture for NTM, or biopsy w/ mycobacterial histopathologic features (granulomatous formation or acid-fast stain) & ≥1 sputum or bronchial wash/lavage culture positive for NTM

Physical Examination

  • May reflect underlying lung pathology
  • Chest auscultation may reveal rhonchi, crackles, wheezes
  • Characteristic body morphotype is noted especially in nodular/bronchiectatic M avium complex (MAC) pulmonary disease

Laboratory Tests

Sputum Exam for Acid-Fast Bacilli (AFB)

  • Preferably 3 early-morning sputum specimens must be collected on separate days
  • Fluorochrome technique is the recommended method
  • If rapidly growing mycobacteria (RGM) is suspected, it is advised to use weaker decolorizing process
  • Semiquantitative analysis may be useful in the diagnosis

Bronchoscopy

  • Considered in patients who are unable to produce sputum
  • May be done w/ or w/o lung biopsy

Sputum Culture

  • All cultures should include both solid & liquid (broth) media
  • Liquid media produce rapid results & have higher yield of mycobacteria
  • Advantages of solid media are the following: Allow recognition of mixed infections, observation of colony morphology & growth rates, quantitation of organism, & serve as a substitute when liquid media cultures are contaminated
  • Quantitation of the number of colonies is recommended

Lung Biopsy

  • May be done in patients w/ nondiagnostic radiographic & microbiologic findings, or if there is concern on the presence of other disease causing radiographic abnormalities

Antimicrobial Susceptibility Testing

  • Clarithromycin susceptibility testing is recommended for MAC isolates
  • M kansasii strains are tested for Rifampin; strains that are susceptible to Rifampin will also be susceptible to Rifabutin
    • Strains that are resistant to Rifampin should be tested against a panel of ancillary antimicrobials (eg Ethambutol, Isoniazid, Clarithromycin, Amikacin, fluoroquinolones, & sulfonamides)
    • Testing for M terrae-M nonchromogenicum group, M simiae, M szulgia, & M celatum are the same as w/ M kansasii strains
    • M xenopi testing is the same as M kansasii, but w/ the temperature adjusted to 42-45oC
    • M malmoense testing is the same as M kansasii, but w/ the pH adjusted to pH 6
  • Susceptibility testing for RGM (eg M fortuitum, M abscessus & M chelonae) includes Amikacin, Doxycycline, fluoroquinolones, sulfonamide or Co-trimoxazole, Cefoxitin, Clarithromycin, Linezolid, Tobramycin (for M chelonae), & Imipenem (for M fortuitum)
    • M fortuitum group is easily identified by using Polymixin-B or sulfonamides
    • Testing w/ Cefoxitin or Tobramycin is useful in identifying presence of M abscessus & M chelonae
  • Susceptibility testing for fastidious slow growing NTM is limited
    • M haemophilum are tested using hemin or ferric ammonium citrate in 28-30oC temperatures
    • M genavense are tested in a macrobroth system incubated for >6 weeks; M ulcerans for 4-6 weeks at 30oC

Other Laboratory Tests

  • Rapid species identification of NTM should be routinely done through DNA probes & high-performance liquid chromatography (HPLC)
  • RGM (especially M chelonae, M abscessus & M fortuitum) isolates should be identified using extended antibiotic in vitro susceptibility testing, DNA sequencing, or polymerase chain reaction (PCR) restriction endonuclease assay (PRA)
  • Baseline tests are necessary to assist in monitoring for efficacy & adverse effects of antimicrobial drugs & for the development of drug resistance
  • Request for complete blood count, renal function, liver function tests (LFT) prior to initiation of drugs
  • Testing for visual acuity, red-green color discrimination & hearing are advised at baseline
Baseline Laboratory Evaluations
  • Baseline tests are necessary to assist in monitoring for efficacy & adverse effects of antimicrobial drugs & forthe development of drug resistance
  • Request for complete blood count, renal function, liver function tests (LFT) prior to initiation of drugs
  • Testing for visual acuity, red-green color discrimination & hearing are advised at baseline

Imaging

  • Findings depend on whether the pulmonary disease is characterized by nodules & bronchiectasis (nodular/bronchiectatic disease) or predominantly fibrocavitary (similar to TB)
  • Plain chest X-ray may be adequate to evaluate fibrocavitary lung disease, whereas HRCT of the chest is recommended to evaluate nodular/bronchiectatic pulmonary disease
  • Findings on hypersensitivity-like pulmonary disease may include ground glass opacities as well as mosaic pattern as noted on HRCT scan
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