Pulmonary Nontuberculous Mycobacterial Infections

By Elliott Dasenbrook, MD

Pulmonary nontuberculous mycobacterial (NTM) infections due to organisms such as Mycobacterium avium complex (MAC) and Mycobacterium abscessus are being diagnosed with increasing frequency. These organisms are commonly recovered on sputum or bronchoscopic cultures obtained as part of an evaluation for an abnormal CT scan of the chest demonstrating multiple pulmonary nodules or bronchiectasis. Below is a thoracic CT of a patient with MAC lung disease and characteristic radiologic findings of centrilobular nodules and tree-in-bud opacities in the bilateral lower lobes in the setting of underlying diffuse bronchiectasis.

The diagnosis of NTM infection is often less than straightforward, and decisions regarding treatment of NTM infections can be complicated. Sometimes patients have underlying chronic lung disease that may need to be addressed first. Expert consultation is often warranted.

Diagnosis of NTM lung disease

Both clinical and microbiologic criteria must be met for a diagnosis of NTM lung disease. The below table shows the diagnostic benchmarks from the American Thoracic Society and Infectious Disease Society of America. These criteria help differentiate true infection from a transient infection or colonization.

It is important to note that since patients with NTM frequently have underlying chronic pulmonary conditions, these should be treated first. For example, patients with bronchiectasis may be co-infected with Pseudomonas aeruginosa. Clinicians should treat the P. aeruginosa first, then reevaluate the symptoms and imaging.

Diagnosis does not imply treatment

Discovery of NTM lung disease does not necessarily mean physicians should immediately begin treatment. Lung disease from these infections progresses slowly, so there is time to evaluate whether NTM or a transient infection or colonization is responsible for the patient’s clinical symptoms and/or radiographic abnormalities.

If clinical and microbiologic criteria are met, then clinicians can discuss with the patient the risks and benefits of therapy. The length of drug therapy is typically a minimum of 18 months and at least 12 months from the time cultures have turned negative. The medication regimen requires monthly monitoring, and patients often report difficulty managing the gastrointestinal side effects.

Importance of airway clearance

The majority of patients with pulmonary NTM have underlying lung disease such as bronchiectasis, chronic obstructive pulmonary disease and cystic fibrosis. In addition to treatment of the airway infection, it is important to address airway clearance. A frequently used, twice-daily regimen for airway clearance consists of nebulized albuterol followed by nebulized hypertonic saline (3 percent or 7 percent), and then use of a positive expiratory pressure device with airway vibration, such as the acapella® Vibratory PEP Therapy System.

In addition, many patients will mobilize secretions with exercise. If a patient qualifies for pulmonary rehabilitation, this is an excellent option. If they do not qualify, then clinicians can suggest a program consisting of cardiovascular and core strengthening with a goal of 150 minutes per week.

Treatment: When to consider expert consultation

Medical regimens for NTM are complex. They can consist of oral, intravenous and inhaled antibiotics that are not routinely encountered in clinical practice, and monitoring for side effects and toxicities should occur at least monthly. Thus, outside expertise may be needed.

The following situations may warrant referral:

• Patients with macrolide-resistant MAC. If patients are still culture positive after six months of therapy, macrolide susceptibility should be checked. Those with macrolide-resistant organisms may require additional second-line agents.
• Refractory MAC patients: Individuals, for instance, who are treated for 12 months with triple therapy (most commonly ethambutol, rifampin and azithromycin) for MAC lung disease and remain culture positive
• Patients who are culture positive for Mycobacterium abscessus or other less common NTM
• Patients for whom surgery is being considered as an adjunct to medical therapy
• Patients who are immunocompromised

At Cleveland Clinic, our NTM Program brings together experts from infectious disease, pulmonary medicine and respiratory therapy who collaborate with patients in the diagnosis and treatment of these difficult-to-treat pulmonary NTM infections.