refractory MAC Pulmonary Disease Treatmenet

Mycobacterium avium complex (MAC) pulmonary disease is a challenging condition to treat, particularly when standard therapies fail. When patients continue to test positive for MAC despite undergoing treatment, the disease is considered refractory. Here we will explore what refractory MAC pulmonary disease is, how it’s diagnosed, and the steps that can be taken to try and eradicate the infection.

Understanding Refractory MAC Pulmonary Disease

MAC is a type of nontuberculous mycobacteria (NTM) found in water and soil. It can be inhaled into the lungs, causing infection, especially in individuals with underlying lung conditions. Standard treatment typically involves a multi-drug regimen, including a macrolide (such as clarithromycin or azithromycin), ethambutol, and rifampin, administered for at least 12 months after culture conversion. Culture conversion occurs when the patient’s sputum cultures are consistently negative for MAC.

Refractory MAC pulmonary disease occurs when patients do not achieve culture conversion after at least six months of standard therapy. This can happen due to various factors, including drug resistance, inadequate drug absorption, or an incorrect diagnosis.

Diagnosing Refractory MAC Pulmonary Disease

Diagnosis of refractory MAC involves confirming persistent infection despite ongoing treatment. It is recommend obtaining three sputum specimens done at separate times, with at least two positive cultures required for confirmation. This helps distinguish between true infection and environmental contamination.

Strategies for Treating Refractory MAC

When standard treatment fails, several approaches can be considered:

  1. Optimised Drug Regimen: Adjusting the existing antibiotic regimen based on drug susceptibility tests can help. This might involve higher doses or different combinations of antibiotics to target the resistant strains effectively.
  2. Amikacin Liposome Inhalation Suspension (ALIS): Approved by the FDA in 2018 and available in the UK, ALIS has shown promise for treatment-refractory MAC. This therapy involves inhaling amikacin encapsulated in liposomes, which delivers the antibiotic directly to the lungs, enhancing its efficacy against MAC bacteria.
  3. Intravenous Therapy: In more severe cases, intravenous administration of antibiotics such as amikacin or streptomycin might be necessary. This approach is often combined with oral antibiotics for a comprehensive treatment strategy.
  4. Surgical Intervention: In cases where localised disease does not respond to medical therapy, surgical resection of affected lung tissue may be considered. This is typically reserved for patients with limited disease and good overall health.
  5. Supportive Care: Ensuring optimal nutritional status, managing underlying conditions, and improving overall lung health through pulmonary rehabilitation can support the effectiveness of the treatment and improve the patient’s quality of life.

Amikacin Liposome Inhalation Suspension for Refractory MAC Pulmonary Disease

Amikacin Liposome Inhalation Suspension (ALIS) has emerged as a significant development for patients with refractory MAC. Clinical trials have demonstrated its efficacy in patients who have not responded to standard therapy. One pivotal trial, the CONVERT study, evaluated the safety and efficacy of ALIS in combination with guideline-based therapy. The study included patients with refractory MAC who had failed at least six months of prior treatment.

The trial showed that adding ALIS to guideline-based therapy significantly increased the proportion of patients achieving culture conversion compared to guideline-based therapy alone. At six months, 29% of patients in the ALIS plus GBT group achieved culture conversion versus 8.9% in the guideline-based therapy alone group. These results highlight the potential of ALIS as a crucial tool in managing refractory MAC pulmonary disease.

Intravenous Amikacin

Intravenous (IV) amikacin remains an option for treating refractory MAC, especially in severe cases. Data from various studies indicate that IV amikacin can be effective when used as part of a combination regimen. However, it is typically reserved for patients who can tolerate its potential side effects, which include nephrotoxicity and ototoxicity.

In clinical practice, IV amikacin is often administered for a limited duration, followed by oral therapy to minimise the risk of adverse effects. The exact duration and combination of antibiotics should be tailored to the individual patient’s response and tolerance to the treatment.

Balancing Treatment and Adverse Effects

Managing refractory MAC pulmonary disease is a delicate balance between achieving disease control and minimising adverse effects. Long-term antibiotic therapy can lead to various side effects, including gastrointestinal disturbances, hepatotoxicity, and drug interactions.

  1. Monitoring and Adjusting Treatment: Regular monitoring of liver function, kidney function, and hearing is essential for patients undergoing prolonged antibiotic therapy. Adjusting the treatment regimen based on these tests can help mitigate adverse effects.
  2. Patient-Centred Approach: It’s crucial to involve patients in treatment decisions, discussing the potential benefits and risks of continued therapy. Some patients may opt for a less aggressive approach if the side effects significantly impact their quality of life.
  3. Supportive Care and Symptom Management: Providing supportive care to manage symptoms and prevent complications can improve patient outcomes. This includes nutritional support, pulmonary rehabilitation, and management of comorbid conditions such as bronchiectasis.

When Eradication of MAC Isn’t Possible

In some cases, complete eradication of MAC may not be achievable. The focus then shifts to managing symptoms and preventing disease progression:


Refractory MAC pulmonary disease presents significant challenges, but understanding this pulmonary infection and available treatment options can improve outcomes. An expert respiratory physician with expertise in chest infections and bronchiectasis can help you manage your NTM pulmonary disease even if refractory. Optimised antibiotic regimens, new therapies like nebulised liposomal amikacin, and supportive care strategies are pivotal in managing this complex condition. For those who do not achieve eradication, long-term management and regular monitoring can help maintain a better quality of life.


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Disclaimer: The information provided in this article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your healthcare provider with any questions you may have regarding a medical condition or treatment

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