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.

Principles of Therapy

  • Patients suspected of having nontuberculous mycobacterial (NTM) pulmonary disease but do not meet all the criteria should be observed until the diagnosis is confirmed or excluded
  • Patients w/ M avium complex (MAC) pulmonary disease respond well to multidrug therapy, hence it is recommended that antimicrobial treatment be initially administered

Pharmacotherapy

Recommended Treatment Regimens Based on Causative Agent

  • MAC pulmonary disease:
    • Severe nodular/bronchiectatic or patients w/ fibrocavitary disease who cannot tolerate daily therapy: Clarithromycin or Azithromycin + Ethambutol + Rifampicin administered 3x weekly
    • Fibrocavitary or severe nodular/bronchiectatic: Clarithromycin or Azithromycin + Ethambutol + Rifampicin
    • Severe & multilobar especially fibrocavitary or refractory infection: Clarithromycin or Azithromycin + Rifabutin or Rifampicin + Ethambutol w/ or w/o (Amikacin or Streptomycin for 2-3 months)
    • Macrolide-resistance: 4-drug regimen w/ Isoniazid + Rifampicin or Rifabutin + Ethambutol (for 1st 2 months) + Streptomycin (for initial 3-6 months)
  • Pulmonary M kansasii disease: Rifampicin + Isoniazid + Ethambutol
    • Clarithromycin may be substituted for Isoniazid
    • Supplementary Pyridoxine is recommended while on Isoniazid
  • 3-drug regimen for Rifampicin-resistant M kansasii disease: Clarithromycin or Azithromycin + Moxifloxacin + ≥1 drug based on In vitro susceptibilities (eg Ethambutol, Sulfamethoxazole, Streptomycin, or Amikacin)
  • M abscessus pulmonary disease: Clarithromycin or Azithromycin + ≥1 drug (Amikacin, Cefoxitin or Imipenem)
    • Amikacin w/ Cefoxitin or Imipenem is recommended for initial treatment of patients w/ M abscessus subspecie bolletii w/out prior history of therapy, & for the whole duration of treatment for M abscessus subspecie abscessus
    • Linezolid, Tigecycline, Doxycycline, Ciprofloxacin, Levofloxacin, or Moxifloxacin monotherapy may also be used
    • Difficult to treat medically, hence surgery is advised
  • Pulmonary M chelonae infection: Tobramycin, Amikacin, Clarithromycin or Azithromycin, Linezolid, Moxifloxacin, Ciprofloxacin, Doxycycline, Imipenem
  • M xenopi pulmonary infection: Rifampin + a macrolide (Clarithromycin or Azithromycin) + Ethambutol w/ Moxifloxacin
  • For M fortuitum lung disease, ≥2 of the following are recommended: fluoroquinolones, sulfonamides, Imipenem, Doxycycline, Cefoxitin, aminoglycosides
  • M malmoense pulmonary disease: Rifampin + Ethambutol w/ or w/o Isoniazid + fluoroquinolones + a macrolide
  • M simiae lung infection: a macrolide (Clarithromycin or Azithromycin) + fluoroquinolones (preferably Moxifloxacin, or Ciprofloxacin) + a sulfonamide
  • Hypersensitivity-like pulmonary disease especially severe form or in respiratory failure: Corticosteroids (Prednisone) given 1-2 mg/kg/day tapered over 4-8 weeks
    • Antimicrobials against MAC are indicated in the following patients: immunocompromised, w/ persistent disease after removal of MAC antigen exposure, w/ bronchiectasis

Amikacin

  • Most active drug against M abscessus
  • May be used as an alternative drug to Streptomycin especially in macrolide-resistant MAC pulmonary disease

Cefoxitin

  • Effective against M abscessus

Ethambutol

  • One of the 1st-line drugs for MAC disease therapy
  • Effective against M kansasii especially in combination therapy w/ Isoniazid & Rifampicin
    • Regimen has low failure & relapse rates in Rifampicin-susceptible strain

Imipenem

  • Alternative agent to Cefoxitin in the treatment of M abscessus pulmonary infection

Macrolides

  • Eg Clarithromycin, Azithromycin
  • Major agent in the treatment of MAC pulmonary disease & M abscessus subsp bolletii
  • Not recommended as monotherapy to prevent emergence of resistance
  • Have substantial In vitro & clinical activity against MAC & M abscessus & M kansasii
    • Clarithromycin is recommended as an alternative for Rifampicin-resistant M kansasii isolates
  • Clarithromycin enhances Rifabutin toxicity

Moxifloxacin

  • Has an excellent In vitro activity against M kansasii, hence may be effective in re-treatment regimens

Rifampicin

  • Rifamycin of choice against MAC & M kansasii
  • Has synergistic effect w/ Ethambutol against MAC

Rifabutin

  • Affects the metabolism of Clarithromycin
  • Reserved for use as a substitute for Rifampicin

Tigecycline

  • Has an excellent In vitro activity against M abscessus

Tobramycin

  • Preferred therapy for M chelonae

Duration of Antimicrobial Therapy

  • The recommended treatment duration for MAC & M kansassi is 12 months of negative sputum cultures
  • For Rifampin-resistant M kansassi isolates, therapy should be continued until sputum culture negative for 12-15 months
  • Treatment duration of 2-4 months is advised to obtain clinical & microbiological improvement in patients w/ M abscessus pulmonary disease

Surgical Intervention

  • May be advised in the following conditions: Localized lung involvement, tolerant to resectional surgery, development of macrolide-resistance, treatment failure, presence of disease-related complications, recurrent disease
  • May be considered in patients w/ severe & multilobar MAC disease or who are resistant to macrolide therapy
  • Surgical resection of involved lung combined w/ multidrug therapy is predictably curative in patients w/ M abscessus pulmonary disease
  • Not indicated in patients infected w/ M kansasii due to excellent prognosis w/ antimicrobial therapy

Treatment Failure

Factors to consider in treatment failure:

  • Noncompliance
  • Intolerance to side effects
  • Emergence of antimicrobial resistance
  • Anatomic limitations (eg focal cavitary or cystic disease)
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