Pulmonary Mycobacterium avium complex disease
Introduction
Published data to inform the treatment of pulmonary Mycobacterium avium complex disease are limited. If treatment is indicated, a combination of three drugs is required for the entire treatment course. Test sputum regularly for mycobacteria while the patient is being treated. The duration of treatment depends on clinical, microbiological and radiological responses, with treatment continued for at least 12 months from the time the patient’s sputum first becomes culture-negative. The usual duration of treatment is 18 to 24 months.
Clarithromycin susceptibility testing of Mycobacterium avium complex isolates is recommended in patients who do not respond to treatment with macrolide-containing regimens. Except for macrolides, there is poor correlation between Mycobacterium avium complex in vitro drug susceptibility and clinical response to treatment. For management of resistant organisms, severe disease or a poor response to initial treatment, see here.
A daily or intermittent (three-times-weekly) treatment regimen can be used. An intermittent regimen is not recommended for patients with cavitary disease, moderate or severe disease (eg multilobar disease), those who have been previously treated for Mycobacterium avium complex, and those who are immunocompromised.
Daily treatment regimen
For daily treatment of pulmonary Mycobacterium avium complex infection, a three-drug regimen (including a macrolide, ethambutol and a rifamycin) is required; use:
1 azithromycin 250 mg (child: 5 mg/kg up to 250 mg) orally, daily12 MAC, pulmonary disease: daily regimen azithromycin
OR
1 clarithromycin 500 mg (adult less than 50 kg or older than 70 years: 250 mg; child: 12.5 mg/kg up to 500 mg) orally, 12-hourly. For dosage adjustment in adults with kidney impairment, see clarithromycin dosage adjustment MAC, pulmonary disease: daily regimen clarithromycin
PLUS (with either of the above regimens)
ethambutol (adult and child) 15 mg/kg orally, daily3. For dosage adjustment in adults with kidney impairment, see ethambutol (daily regimen) dosage adjustment MAC, pulmonary disease: daily regimen ethambutol
PLUS EITHER
1 rifampicin 600 mg (adult less than 50 kg: 450 mg; child 50 kg or more: 600 mg; child less than 50 kg: 15 mg/kg up to 450 mg) orally, daily. For dosage adjustment in adults with kidney impairment, see rifampicin dosage adjustment MAC, pulmonary disease: daily regimen rifampicin
OR
2 rifabutin 300 mg (child: 5 mg/kg up to 300 mg) orally, daily. MAC, pulmonary disease rifabutin
Staged introduction of the drugs at 1-week intervals is prudent in the elderly, to make it easier to attribute adverse effects to a particular drug. Gradually introduce the macrolide over 1 to 2 weeks, then add ethambutol, followed by the rifamycin. Adverse effects of therapy, particularly nausea, may require dose reduction or a trial of evening dosing. The macrolide and ethambutol are likely more important in the treatment of Mycobacterium avium complex than rifampicin, and rifampicin is sometimes omitted or substituted with another drug if it causes troublesome adverse effects. Clofazimine has been used as an alternative to one of the other drugs in the event of adverse effects.
Monitor vision because ethambutol can cause visual adverse effects (see Monitoring tuberculosis therapy).
Intermittent (three-times-weekly) treatment regimen
An intermittent regimen is not recommended for patients with cavitary disease, moderate or severe disease (eg multilobar disease), those who have previously been treated for pulmonary Mycobacterium avium complex, and those who are immunocompromised.
If intermittent treatment of pulmonary Mycobacterium avium complex infection is appropriate, a three-drug regimen (including a macrolide, ethambutol and rifampicin) is required; use:
1 azithromycin 500 mg (child: 10 mg/kg up to 500 mg) orally, 3 times weekly4 MAC, pulmonary disease: intermittent regimen azithromycin
OR
1 clarithromycin 500 mg (child: 12.5 mg/kg up to 500 mg) orally, 12-hourly (ie two doses per day) on 3 days per week. For dosage adjustment in adults with kidney impairment, see clarithromycin dosage adjustment MAC, pulmonary disease: intermittent regimen clarithromycin
PLUS (with either of the above regimens)
ethambutol (adult and child) 25 mg/kg orally, 3 times weekly5. For dosage adjustment in adults with kidney impairment, see ethambutol (three-times-weekly regimen) dosage adjustment MAC, pulmonary disease: intermittent regimen ethambutol
PLUS
rifampicin (adult and child) 15 mg/kg up to 600 mg orally, 3 times weekly. For dosage adjustment in adults with kidney impairment, see rifampicin dosage adjustment. MAC, pulmonary disease: intermittent regimen rifampicin
Monitor vision because ethambutol can cause visual adverse effects (see Monitoring tuberculosis therapy).
Resistant organisms, severe disease and poor response to initial treatment
Patients infected with a macrolide-resistant isolate require an alternative regimen—seek expert advice. Treatment options may include amikacin for the first 2 months of treatment (daily or three times weekly).
Therapeutic options for patients with severe disease or a poor response to initial treatment include the addition of an aminoglycoside, clofazimine or interferon gamma.
Surgical resection of focal disease or a solitary nodule or cavity is sometimes indicated.
For more information on managing macrolide-resistant and severe pulmonary Mycobacterium avium complex infections (including amikacin regimens and monitoring), see the British Thoracic Society Guidelines for the Management of Non-tuberculous Mycobacterial Pulmonary Disease (NTM-PD) (2017) [URL].