What is the next step for a patient with Mycobacterium Avium Complex (MAC) pulmonary disease who remains culture positive after six months of treatment?

From the Guidelines

For a patient with Mycobacterium Avium Complex (MAC) pulmonary disease who remains culture positive after six months of treatment, the next step is to add amikacin liposome inhalation suspension (ALIS) to the guideline-based therapy, as it has been shown to improve culture conversion and is now approved by the US Food and Drug Administration for this indication 1. The clinician should first ensure medication adherence and then obtain drug susceptibility testing to guide therapy adjustments.

• The standard approach is to intensify the regimen by adding one or two additional antibiotics,
• The core medications (macrolide, ethambutol, and rifamycin) should be continued if tolerated.
• Additionally, the clinician should consider therapeutic drug monitoring to ensure adequate serum levels,
• Evaluate for potential drug interactions,
• Reassess whether the patient might benefit from adjunctive therapies such as airway clearance techniques or surgical resection for localized disease. Persistent positive cultures indicate inadequate treatment response, which may be due to drug resistance (particularly to macrolides), inadequate drug concentrations, or anatomical factors that limit drug penetration to infection sites. The use of ALIS has been associated with a higher proportion of patients with negative cultures at 6 months compared to those who continued to take the standard regimen only, with culture conversion achieved by 29.0% of patients with ALIS + guideline-based therapy compared with 8.9% with guideline-based therapy alone 1. However, the addition of ALIS may also increase the risk of adverse events, such as dysphonia, cough, and respiratory events, which should be carefully monitored and managed 1. It is also important to note that the use of ALIS may lead to the development of amikacin resistance, which should be closely monitored through regular drug susceptibility testing 1. Overall, the addition of ALIS to guideline-based therapy is a recommended approach for patients with MAC pulmonary disease who remain culture positive after six months of treatment, and its use should be carefully considered and monitored by a qualified healthcare professional 1.

From the Research

Next Steps for MAC Pulmonary Disease Treatment

• For a patient with Mycobacterium Avium Complex (MAC) pulmonary disease who remains culture positive after six months of treatment, the next steps may involve:
  • Re-evaluation of the current treatment regimen and consideration of alternative treatment options 2
  • Addition of other drugs such as aminoglycoside, amikacin liposomal inhalation, clofazimine, linezolid, bedaquiline, or fluoroquinolone to the current regimen 2
  • Surgical lung resection may be considered in cases where the disease is localized and the patient has a high risk of treatment failure or macrolide resistance 3, 4
• The treatment duration for MAC pulmonary disease is typically at least one year after culture conversion, but this may vary depending on the individual patient's response to treatment and the presence of any underlying conditions 3, 2
• It is essential to monitor the patient's response to treatment and adjust the regimen as needed to prevent the development of macrolide resistance and ensure the best possible outcome 5, 2

Considerations for Treatment Failure

• Treatment failure or macrolide resistance can occur in patients with MAC pulmonary disease, and alternative treatment options may need to be considered 3, 2
• The use of ethambutol has been shown to prevent macrolide resistance, and its concomitant use with other drugs may be beneficial in preventing treatment failure 2
• Intermittent treatment with azithromycin and ethambutol may be an optional treatment regimen for noncavitary MAC pulmonary disease, but its efficacy and safety need to be further evaluated 6

Importance of Multidisciplinary Approach

• A multidisciplinary approach to the management of MAC pulmonary disease is crucial, involving collaboration between healthcare professionals, including infectious disease specialists, pulmonologists, and surgeons 3, 4
• The decision to initiate long-term antibiotic treatment should be made carefully, taking into account the patient's individual circumstances and the potential risks and benefits of treatment 3