Nontuberculous%20mycobacterial%20disease Treatment

• 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

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

• 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

Factors to consider in treatment failure:

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