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NTM Treatment
How to Approach Treatment of NTM Lung Disease

Released: September 29, 2023

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Key Takeaways
  • NTM lung disease treatment is complex and long-lasting and should be approached using guideline recommendations.

On Thursday, October 12, I will be part of a symposium at IDWeek 2023 in Boston, Massachusetts, focused on best practices for treating people living with nontuberculous mycobacterial (NTM) lung disease. I invite you to read more about this topic below and then register to hear more at the live interactive symposium, either in person or virtually.

The management of NTM lung disease can be challenging given the need for a multidrug regimen frequently associated with adverse events. A multisociety-sponsored NTM guideline is available to assist healthcare professionals with treatment of some of the most common causes of NTM lung disease, such as members of Mycobacterium avium complex (MAC).

Initiation of Treatment or Watchful Waiting
The NTM guideline suggests that, in people who meet the diagnostic criteria for NTM lung disease, initiation of treatment rather than watchful waiting is warranted, especially when positive acid-fast bacilli sputum smears and/or cavitary lung disease are present. Studies have identified risk factors that are associated with a higher rate of disease progression and can be helpful in deciding whether to initiate treatment:

  • Host factors: male sex, older age, comorbidities, and low BMI (<18.5 kg/m2)
  • Laboratory-related factors: include elevated inflammatory markers, anemia, and hypoalbuminemia
  • Radiographic factors: fibrocavitary disease or more extensive disease
  • Microbial factors: causative species and/or bacterial load

Even when antimicrobial therapy is not initiated, patients with bronchiectasis should initiate good airway clearance techniques using oscillating positive expiratory pressure (PEP) valves, high-frequency chest wall oscillation, and/or hypertonic saline. In addition, exercise capacity, nutritional status, and gastroesophageal reflux should be assessed.

Antimicrobial Susceptibility Testing
Antimicrobial susceptibility testing against MAC is recommended before embarking on treatment. The NTM guideline and Clinical and Laboratory Standards Institute recommend that amikacin and clarithromycin (representative for macrolides) be tested, as these are the only drugs for which resistance cut points have been correlated with clinical outcomes. For M. kansasii, rifampin and clarithromycin should be tested, and for M. abscessus, clarithromycin and amikacin should be tested. In addition, the isolate should be examined to determine if a functional erm(41) gene is present so that you know if inducible macrolide resistance is present.

Treatment of MAC Lung Disease
For macrolide-susceptible MAC lung disease, the specific treatment regimen varies based on the phenotype. For nodular-bronchiectatic disease, a 3-drug, macrolide-based regimen is recommended and can be administered 3 days a week. For cavitary disease or otherwise extensive disease, the same drugs are used, but parenteral amikacin is recommended for the first 2-3 months, and the oral regimen is administered daily with dose adjustments. Surgical resection should be considered as an adjunct to drug therapy. Treatment should continue for at least 12 months beyond culture conversion.

Culture conversion occurs in 76% to 88% of patients with macrolide-susceptible, noncavitary MAC lung disease and often is lower in those with cavitary disease. Microbiologic recurrence after conversion is common—occurring in 25% to 48% of patients—and 46% to 75% of these are due to reinfections.

Patients who remain culture positive after at least 6 months of therapy are considered treatment refractory and should have amikacin liposome inhalation suspension (ALIS) added to their guideline-based regimen. The CONVERT study demonstrated that patients with treatment-refractory MAC lung disease who had ALIS added to their guideline-based therapy were significantly more likely to convert cultures to negative by 6 months (29% vs 8.9%; P <.001) than those who continued treatment without addition of ALIS.

Treatment outcomes in patients with macrolide-resistant MAC are poor. Factors associated with better outcomes include surgical resection with prolonged aminoglycoside use and C-reactive protein <1.0 mg/dL. No difference in outcomes has been noted with continuation of the macrolide or addition of a fluoroquinolone, and worsened outcomes have been reported when ethambutol was stopped or when cavitary disease was present.

When building a treatment regimen for macrolide-resistant MAC, I would continue ethambutol, stop the macrolide, consider rifabutin in place of rifampin, add parenteral amikacin, and consider surgical resection. Use of 1-2 additional drugs to replace the macrolide also is recommended, as is consultation with an expert.

Treatment of M. kansasii and M. xenopi
Rifampin-susceptible, nodular bronchiectatic lung disease caused by M. kansasii should be treated with a macrolide-based 3-drug regimen that can be given either 3 times a week or daily, whereas for cavitary disease, daily administration is suggested. An alternative regimen would replace the macrolide with isoniazid and be administered daily. Different from MAC, treatment should continue for at least 12 months, and there is no recommended treatment after culture conversion.

Treatment of M. xenopi is challenging. The NTM guideline suggests addition of azithromycin and/or moxifloxacin plus ethambutol and rifampin with addition of parenteral amikacin when cavitation is present. Surgical resection should be considered for these patients.

Monitoring
Patients started on treatment should be monitored for treatment response with monthly sputum cultures. Monitoring for adverse events should be individualized based on treatment regimen, age, comorbidities, concurrent medications, overlapping medication toxicities, and resources available.

We will explore more about NTM management at our interactive panel discussion–based symposium at IDWeek 2023, including strategies for timely diagnosis, treatment approaches for the most common NTM pathogens, and emerging data on M. abscessus. You can join us in person or by live webcast to hear expert faculty provide perspectives and recommendations on managing complex patient cases.

Your Thoughts?
What proportion of your patients with NTM lung disease convert to negative cultures after receiving a guideline-based treatment regimen? Join the discussion by posting a comment.