Non-TB Mycobacterial Infections of the Lung (Miniae, 7/21/2021)

Thanks to our new(ish) SMGR Pulmonologist, Dr. Mike Minaie, we all know a LOT more about Non-TB Mycobacterial Infections of the lung (NTM) after the excellent Grand Rounds he gave this week on the topic. 

First a random literary malady allusion: NTM is sometimes called "Lady Windemere Syndrome" in reference to a Victorian era character from an Oscar Wilde play (see above) who suffers a chronic cough and malady and is unable to cough and spit (because she has to be 'ladylike' in Victorian times). Historically it was believed that NTM (often presenting in thin post/perimenopausal women) was made pathogenic by the act of suppressing one's cough. Not sure the premise is quite correct. . . 

For those of you who would like to see the entire presentation, it can be found HERE.

For those of you who prefer my Cliff's notes, here goes:

• NTM is generally a subacute infection (symptoms occur over weeks, even months)
• NTM is NOT contagious
• NTM is often recurrent 
• Symptoms of NTM include non-specific complaints, e.g. night sweats, weight loss,  shortness of breath, low grade fever, hemoptysis as well as chronic cough (often with thick sputum) x months

Many NTM-- e.g. mycobacterium avium complex (MAC), are readily present in soil, air, and water. People with intact immune systems may be exposed to these mycobacterium (and even incidentally or transiently acquire them in their respiratory tract) but a the healthy immune system is generally able to clear the NTM without disease.

In contrast, patients who are immunocompromised (e.g. chronic steroid use, HIV) may be less successful in clearing the NTM from their airway, and then the mycobacterium can become pathogenic.

There are a variety of NTM, including those more commonly found (MAC/MAI, M Kansasli) and less common (M maxium, M. xenopi, M simiae). They are also often classified as slow growing (2-4 weeks) vs. rapid growing (4-8 weeks). Different varieties tend to be  regional (e.g. M Abscessus is more frequently encountered in these parts). 

CT findings in NTM are various:

• ground glass lesions
• evidence of bronchiectasis (straw-like lesions on CT)
• solid nodules
• cystic changes
• fibrosis

Diagnosis of NTM is accomplished via BOTH clinical and microbiological assessments:

1. clinical: pulmonary symptoms AND appropriate exclusion of other diseases (e.g. bacterial pneumonia, cancer, COPD)
2. microbiologic (+ culture from at least TWO expectorated sputum spaced out by ONE MONTH, or +culture from a single bronchoscopy sample, or transbronchial or other biopsy with mycobacterial features)

Does NTM always need to be treated?

The answer is NO, if the patient is asymptomatic and/or if symptoms resolve spontaneously (which is often seen in immunocompetent hosts). If you get a single +NTM in sputum but then does not recur, assume the immune system cleared the NTM itself. 

Indications for therapy:

• respiratory or constitutional symptoms with radiographic abnormalities
• recurrent/consistent isolation of NTM in  moderate to high numbers (i.e. not trace amounts on a single sample)
• histologic evidence of pulmonary parenchymal involvement

Treatment:

usually starts IV, then transitions to PO

often lasts >1 year (time starts at first CLEAR sputum)

3 drug abx regimen for MAC (e.g.) is typically: 

• Clarithromycin (1000mg three times per week) OR azithromycin (500mg three times/week) AND
• Rifampin (600mg thrice weekly) AND
• Ethambutol (25mg/kg thrice weekly)

Surgery can be considered in certain circumstances: if disease is isolated to a particular part of the lung, or there is a very large cavity (>8cm, risk of rupture and bleed is high: 50% in 2 years). Surgery may also be indicated if cultures don't clear after 6 months of active treatment. If patient cannot tolerate oral treatment. If they have macrolide resistance

Side effects of the 3 drug cocktail are many: GI intolerance, low WBC, impaired visual acuity and color vision, decreased auditory function, decreased renal function, peripheral neuropathy

NOTE: If patients are on the three drug regimen, be sure to monitor them for vision changes (risk of optic neuritis) is moderate, and meds may need to be stopped (particularly ethambutol, rifampin). Also tinnitus is a sign of macrolide toxicity, which must be stopped immediately in the setting of tinnitus

Also remember there is radiologic lag, so radiographic findings should not be used to guide treatment duration; but rather, clinical improvement and clearing of cultures.

And lastly, don't suppress that cough!