MAI Pneumonia in the Non-Immunosuppressed Patient
Mycobacterium tuberculosis (TB) is a well recognized problem worldwide but there are many “cousins” of tuberculosis from the family called mycobacterium. Some of these “cousins” can cause serious diseases in there own right, while others are still considered “non-pathogenic” or virtually harmless. One of these non-tuberculous mycobacterium (NTM), called MAC or MAI for short, can cause a serious widespread-infection in HIV or immunosuppressed patients. Only since the late 1980’s, however, have we come to recognize MAC as a cause of infection in otherwise healthy individuals.
What is MAC? Mycobacterium avium complex (MAC) includes the two species M. avium and M. intracellularae (or MAI for mycobacterium avium intracellularae). Among the NTM, MAC is the most common cause of pulmonary disease worldwide.
Where does MAC come from?: It is generally felt that these organisms are acquired from the environment. Mycobacteria other than M. tuberculosis and M. leprae (cause of leprosy) are generally free-living organisms that are ubiquitous in the environment. They have been recovered from surface water, tap water, soil, domestic and wild animals, milk, and food products. These organisms can also inhabit body surfaces or secretions without causing disease. Thus, occasional isolates of nontuberculous mycobacteria (NTM) were largely considered contaminants or colonizers until the second half of this century. Unlike TB, there are no solid data demonstrating human to human transmission of MAC. Why some people are infected by MAC and others are not is a still a mystery. It likely has something to do with a persons immune own system and susceptibility to certain infections.
What are the symptoms of MAC? The symptoms and signs of MAC lung disease are variable and non-specific. They include cough (productive or dry), fatigue, malaise, weakness, dyspnea, chest discomfort, and occasionally coughing up blood (hemoptysis). Fever and weight loss occur less frequently than in patients with typical tuberculosis.
Is MAC just one disease? Three major clinical presentations in non-immunosuppressed patients have been described:
The first to be described occurs primarily in middle-aged or elderly men, often alcoholics and/or smokers with underlying chronic obstructive lung disease (COPD). The disease resembles typical tuberculosis clinically and by x-ray, with cough, weight loss, upper lung infiltrates, and cavities.
The second presentation is seen in patients in whom MAC develops in areas of prior bronchiectasis. Older adults are also affected, but there is no association with male sex or smoking-related pulmonary disease. Most commonly, patients with prior treated tuberculosis develop symptoms and a new infiltrate in the previously affected lung zone suggesting a relapse of tuberculosis. This pattern is also seen with other types of bronchiectasis including cystic fibrosis.
The third presentation, being recognized now much more frequently, occurs predominantly in postmenopausal, nonsmoking women. Previously thought to represent airway colonization, the serious nature of this disease has become increasingly evident.. Sometimes called the Lady Windermere syndrome, this form of MAC has been noted in elderly women without predisposing lung disease, and can cause x-ray changes (bronchiectasis, lung nodules, etc), a troublesome cough (occasionally with hemoptysis), progressive weight loss, and malaise.
How is MAC Diagnosed? Your physician may initially have difficulty recognizing the disease because the symptoms are so non-specific. Eventually, the diagnosis is made by a careful history and physical exam, obtaining a standard chest x-ray and perhaps a chest CT scan and then collecting sputum for the microbiology lab. MAC can be difficult to isolate and a bronchoscopy to collect secretions (and sometimes biopsies) may be required.
Does MAC have to be treated? Patients may have a progressive course (in one study 19% of patients) with worsening respiratory symptoms and even die from complications of the disease. Some patients are remarkably asymptomatic despite what looks to be severe disease on chest x-ray. The bottom line is we really don’t have a good way to predict the outcome of this disease for any particular patient.
How is MAC treated?: There is still much to learn about the treatment of MAC. Much of what we know comes from treating this bacteria in HIV patients, which may not necessarily be a the same disease. This is a bacteria that, like TB, requires several antibiotics over a prolonged treatment course to eradicate. Usually 3 drugs are used over many months or years (avg ~18 mos). Even though ≥ 90% of people who stay on the medications will have MAC cleared form there pulmonary secretions, there is no guarantee that the mycobacteria will not return at a later date. The biggest problems, however, are the side effects (see below) and the cost of these medications. At a recent check (10/2001) of the typical 3 drug regimen at DrugStore.com®, the monthly cost was $592 (for a ~150 lb person). Surgery (e.g., resection or collapse therapy) may play a role in the treatment of some patients with MAC lung disease. When surgery was initially proposed , drug treatment was much less effective and more surgeons were experienced with this type of surgery. At present, medical management should be considered the first line of management. Surgery may be useful in the following settings: Patients with localized disease, especially upper lobe cavitary disease or patients in whom drugs fail to convert the sputum cultures to negative after six months of continuous treatment. There are some investigational trials with novel treatments; ask your physician about what you may be eligible for.
What are the side effects of the medicines? The most common antibiotics used are usually: azithromycin (Zithromax) or clarithromycin (Biaxin), rifabutin (Mycobutin®) or rifampin (Rifadin®), ethambutol (Myambutal®), and streptomycin. Others less commonly used include clofazizime, ciprofloxacin or sparfloxacin or levofloxacin, ethionamide, and cycloserine. The most common side effects include:
Nausea, GI upset, headache, and skin rashes: any antibiotic
Low cell counts: rifabutin
Impaired visual acuity or color vision: ethambutol or rifabutin
Decreased renal function: streptomycin
Because some of these side effects won’t necessarily be noticed by the patient, periodic lab work must be drawn while on treatment to follow liver function and cell counts. Patients are encouraged to report any worrisome problems to their physician immediately.