Treatment of Non-Tuberculous Mycobacterial (NTM) Pulmonary Disease
Confirm Diagnosis Before Treatment
Meeting diagnostic criteria does not automatically mandate treatment—you must first assess disease severity, progression rate, patient tolerance for prolonged therapy, and species pathogenicity before initiating antibiotics. 1
Diagnostic Requirements (All Must Be Met):
Clinical criteria:
- Pulmonary or systemic symptoms (cough, dyspnea, hemoptysis, weight loss, night sweats) 1
- HRCT showing nodular or cavitary opacities, OR bronchiectasis with multiple small nodules 1
- Exclusion of tuberculosis and other diagnoses 1
Microbiologic criteria (one of the following):
- ≥2 positive sputum cultures with the same NTM species 1
- ≥1 positive bronchial wash/lavage 1
- Lung biopsy showing granulomatous inflammation or AFB plus positive NTM culture 1
Critical caveat: Species identification to subspecies level is mandatory before treatment, as regimens differ dramatically between organisms. 2 A single positive culture for highly pathogenic species like M. kansasii may warrant treatment, while multiple cultures over months may be needed for low-pathogenicity species like M. gordonae. 1
Species-Specific Treatment Regimens
Mycobacterium avium Complex (MAC)
For non-cavitary/mild nodular-bronchiectatic disease:
- Azithromycin 500-600 mg three times weekly 2
- Rifampin 600 mg three times weekly 2
- Ethambutol 25 mg/kg three times weekly 2
For fibrocavitary or severe nodular-bronchiectatic disease:
- Azithromycin 250-500 mg daily OR clarithromycin 500 mg twice daily 1, 2
- Rifampin 450-600 mg daily OR rifabutin 150-300 mg daily 1, 2
- Ethambutol 15 mg/kg daily 1, 2
- Add IV amikacin 10-15 mg/kg three times weekly for first 2-3 months in severe disease 2
Duration: Continue for 12 months after sputum culture conversion. 3
For cystic fibrosis patients: Use daily (not intermittent) regimen with azithromycin, rifampin, and ethambutol. 4, 2 Never use intermittent three-times-weekly therapy in CF. 4
Susceptibility testing: Perform macrolide susceptibility testing on isolates before treatment and if culture conversion fails after 6 months. 1
Mycobacterium abscessus Complex
Intensive phase (3-12 weeks):
- Azithromycin 250-500 mg daily (preferred over clarithromycin) 1, 2
- IV amikacin 10-15 mg/kg daily 1
- PLUS one or more: IV tigecycline 25-50 mg twice daily, IV imipenem 500-1000 mg 2-3 times daily, OR IV cefoxitin 2-4 g 2-3 times daily 1, 2
Continuation phase (12+ months after culture conversion):
- Azithromycin 250-500 mg daily 1, 2
- Inhaled amikacin 590 mg daily (liposomal formulation) OR 250-500 mg daily (parenteral formulation) 1
- PLUS 2-3 oral agents from: minocycline 100 mg twice daily, clofazimine 100-200 mg daily, moxifloxacin 400 mg daily, linezolid 600 mg once or twice daily 1, 2
Susceptibility testing: Test clarithromycin, amikacin, cefoxitin, and preferably tigecycline. 1 Guide but do not dictate drug selection by susceptibility results. 1
Surgical consideration: For localized disease with adequate pulmonary reserve, surgical resection combined with antibiotic therapy offers the best cure chance. 2
Mycobacterium kansasii
Standard regimen:
- Isoniazid 5 mg/kg (up to 300 mg) daily 1, 2
- Rifampin 10 mg/kg (450-600 mg) daily 1, 2
- Ethambutol 15 mg/kg daily 1, 2
Duration: 12 months after culture conversion. 1
Susceptibility testing: Test rifampin only; if rifampin-resistant, test rifabutin, ethambutol, isoniazid, clarithromycin, fluoroquinolones, amikacin, and sulfonamides. 1
Mycobacterium fortuitum
Do not rely on macrolides despite susceptibility testing showing "susceptible"—all M. fortuitum isolates contain inducible erm(39) gene conferring macrolide resistance. 2
Regimen:
- Use at least two agents with demonstrated in vitro activity 2
- Options include: amikacin, cefoxitin, imipenem, fluoroquinolones, doxycycline, trimethoprim-sulfamethoxazole, linezolid 1
- Continue for minimum 12 months after culture conversion 2
Critical Treatment Principles
Never Use Monotherapy
Macrolide monotherapy for any NTM infection is absolutely contraindicated—this is the single most critical error leading to rapid resistance development and treatment failure. 4, 2, 5
- If a patient on chronic azithromycin (e.g., for CF or bronchiectasis) develops a positive NTM culture, immediately discontinue azithromycin until NTM disease is ruled out. 1, 6, 4
- A 2-week washout period may be required before NTM evaluation due to intracellular accumulation of azithromycin. 1, 6
Susceptibility Testing Strategy
Perform susceptibility testing according to CLSI guidelines before treatment initiation. 1, 2
- MAC: Test macrolides and amikacin; use susceptibility-based treatment over empiric therapy. 1
- M. abscessus complex: Test clarithromycin, amikacin, cefoxitin, tigecycline. 1
- M. kansasii: Test rifampin only unless rifampin-resistant. 1
- Rapidly growing mycobacteria: Test all potentially active agents. 1
Important limitation: In vitro susceptibility does not reliably predict clinical outcomes except for macrolides (MAC) and rifampin (M. kansasii). 4, 7 Use susceptibility results to guide but not dictate drug selection. 1
Monitoring During Treatment
Establish monitoring schedule at treatment initiation and implement throughout therapy: 2
- Sputum cultures: Every 4-8 weeks throughout treatment to assess microbiologic response 2
- Audiometry: Baseline and monthly for patients on amikacin or streptomycin 2
- Visual acuity and color discrimination: Baseline and monthly for patients on ethambutol 2
- Renal function: Baseline and monthly for patients on aminoglycosides 2
- Liver function tests: Baseline and monthly for patients on rifamycins, macrolides, or other hepatotoxic agents 2
- HRCT chest: Shortly before starting treatment and at treatment completion to assess radiographic response 2
Common Pitfalls to Avoid
Starting treatment without species identification: Regimens differ dramatically between species; empiric therapy is inappropriate. 2
Using macrolide monotherapy: This rapidly induces resistance and is contraindicated with 100% consensus. 4, 2
Treating all patients who meet diagnostic criteria: Watchful waiting may be appropriate for slow-progressing disease, elderly patients with limited life expectancy, or those unable to tolerate prolonged therapy. 1
Inadequate treatment duration: Continue therapy for 12 months after culture conversion, not from treatment initiation. 2, 3
Ignoring drug-drug interactions: Rifamycins induce cytochrome P450 enzymes and interact with numerous medications; review all concomitant medications before starting treatment. 2
Failing to monitor for toxicity: Extended treatment duration leads to cumulative toxicity; implement structured monitoring protocols. 2
Using intermittent therapy in CF patients with MAC: Daily regimens are required in CF; three-times-weekly dosing is contraindicated. 4, 2