Nontuberculous Mycobacterial Infections Treatment

Treatment Regimen Considerations

For patients with cavitary, extensive nodular/bronchiectatic disease, or macrolide-resistant MAC, the American Thoracic Society recommends adding amikacin as a fourth agent to a regimen containing levofloxacin, azithromycin, and ethambutol 1, 2, 3
For nodular/bronchiectatic MAC disease, a three-drug regimen of azithromycin, rifampin, and ethambutol is typically recommended, administered three times weekly 1, 2
For fibrocavitary or severe nodular/bronchiectatic disease, a daily regimen is preferred with the addition of amikacin or streptomycin early in therapy 1, 2, 3
For refractory MAC disease, amikacin liposome inhalation suspension or parenteral amikacin should be added 2, 3

Amikacin is the most commonly recommended fourth agent for more severe or refractory NTM infections, with dosing at 10-15 mg/kg daily IV or 590 mg daily via liposome inhalation suspension 1, 2, 3
Amikacin is associated with ototoxicity in approximately one-third of patients after 15 weeks of therapy, and drug level monitoring is recommended 2, 4

Treatment should continue until sputum cultures remain negative for 12 consecutive months while on therapy, with monthly sputum cultures obtained to monitor treatment response 5, 6
Macrolide monotherapy should never be used due to the risk of developing macrolide resistance 7, 5
A two-drug regimen of macrolide with only ethambutol may be inadequate for preventing resistance, especially in fibrocavitary disease 5
Close monitoring for drug toxicities is essential, particularly aminoglycoside-related ototoxicity and nephrotoxicity, and ethambutol-related ocular toxicity 4, 3, 8

The treatment algorithm involves assessing disease severity, choosing an amikacin formulation, monitoring for toxicity, and adjusting the regimen based on response 1, 2, 3, 9
For severe disease, IV amikacin is recommended, while for refractory disease, amikacin liposome inhalation suspension may be considered 3
Audiometry and renal function monitoring are essential before treatment and at regular intervals 4, 3