Treatment of MAC requires a multidrug regimen as MAC is resistant to most ordinary antibiotics. Use of only one or two drugs may result in the development of mutations in the MAC so they become resistant to the drugs.

Standard treatment of MAC recommended by the American Thoracic Society (ATS) is a combination of 3 or 4 drugs approved by the Food and Drug Administration (FDA). The drugs include:

Clarithromycin (Biaxin) or Azithromycin (Zithromax)

Rifampin (Rifadin) or Rifabutin (Mycobutin) + Ethambutol (Myambutol)

Streptomycin (Strep) or Amikacin (Amikin)

The first three drugs are pills/capsules and may be given daily or three times weekly (Monday-Wednesday-Friday). While taking these medicines, routine laboratory tests to check kidneys and liver along with a complete blood count (CBC) should be performed, at least routinely for the first six months. Patients who fail therapy after taking the 3 standard medicines (clarithromycin/azithromycin, rifampin/rifabutin, and ethambutol) are usually required to take additional medicines (such as injectables or “shots”) which may be effective. For extensive or severe disease, or disease that has failed therapy, the injectables streptomycin or amikacin are often added for the first 2 to 4 months of therapy.

Amikacin has recently become available in an inhaled form which causes less toxicity than IV or IM administration.

STANDARD DRUGS

Clarithromycin (Biaxin)

Clarithromycin belongs to a class of drugs known as macrolides. It is well absorbed in pill form. It is metabolized in the liver and excreted in part by the kidneys so that a reduction in dosage may be required in elderly patients (kidney function normally declines with age), patients with low body weights, and in patients with known kidney disease.

The most common side effects are metallic (bitter) taste, loss of appetite, nausea, vomiting, and diarrhea. Abnormalities in liver enzymes may also occur, usually in patients on dosages of clarithromycin of more than 1000 mg per day.

Clarithromycin should never be taken alone or combined only with a quinolone drug (includes ciprofloxacin and levofloxacin) for the treatment of MAC because of the risk of the MAC developing resistance to this drug. Clarithromycin is generally taken by mouth at a dosage of 1000 mg daily or 500 mg twice daily or 1000 mg (Biaxin XL) given three times weekly (Mon-Weds-Fri) in adults.

Azithromycin (Zithromax)

Azithromycin is an alternative macrolide drug to clarithromycin which is also well absorbed in pill form. Chemically the two drugs are very similar. Some patients who cannot tolerate clarithromycin, may be able to take azithromycin partly because it has fewer interactions with other drugs (that is it combines with other drugs to cause fewer bad side effects).

Diarrhea and gastrointestinal upset including abdominal pain and nausea may occur. Hearing loss and tinnitus (sounds in ears) are also possible on azithromycin. These are all generally reversible when the drug is stopped or with lower drug doses.

Azithromycin is generally taken by mouth at a dose of 250-500 mg daily or 500 mg three times weekly in adults.

Rifampin (Rifadin)

Rifampin is well absorbed by mouth. Minimal abnormalities in liver function tests (LFTs) are common in patients taking rifampin. Alcoholic patients on rifampin with pre-existing liver damage appear to be especially prone to developing significant abnormalities in the liver enzymes. Gastrointestinal upset including nausea and vomiting may occur. Other side effects such as fever, flushing, and itching without rash may also occur. Blood abnormalities such as a decrease in the blood cells that aid in clotting (platelets) known as thrombocytopenia may occur. Rarely, patients may develop a worsening of kidney function called interstitial nephritis.

Because the orange color of the pills is absorbed in the body, urine, saliva, sputum, tears, sweat, semen, and other body fluids may temporarily appear orange or red for several hours after taking the medicine. With extremely high doses, a condition known as “Redman syndrome” has been described. It should be emphasized, also, that persons on rifampin should not wear soft contact lenses because the lenses will stain orange permanently.

Rifampin is a pill taken by mouth at a standard dose of 300-600 mg daily or 600 mg three times weekly in adults.

Rifabutin (Mycobutin)

Rifabutin is well absorbed by mouth. Pain in the muscles, inflammation of the eye causing pain and blurriness of vision, and a yellow discoloration of the skin may occur in patients taking high doses of rifabutin (more than 300 mg daily). About 1/3 of the patients taking rifabutin have a low white blood cell (these are cells that fight infection) count (also called neutropenia). This is reversible, and has not been associated with an increased risk of infection. The incidence of rash, gastrointestinal upset, including nausea and vomiting and abnormalities of liver enzymes is comparable to that of rifampin and like rifampin, rifabutin may also produce a temporary orange-red discoloration of urine, saliva, tears, and contact lenses. Fever, chills, and a “flu-like” illness often occurs on high drug doses (usually daily).

Rifabutin is a pill taken by mouth at a standard dosage of 150-300 mg daily or three times weekly in adults.

Ethambutol (Myambutol)

The major toxicity effect of ethambutol is associated with nerves including inflammation of the optic nerve in the eye (called optic neuritis). Characteristically, patients complain of blurry vision (usually in both eyes) and often have problems with red-green color discrimination. This is considered a toxicity, and occurs on high daily doses of the medicine. (Allergic reactions, in contrast, may occur on any drug dosage of the medicine.) Ethambutol induced optic neuritis is more likely in patients taking 25 mg/kg/day of ethambutol. Ethambutol optic neuritis appears more common on daily therapy than on three times weekly therapy. Usually after stopping the drug, the condition slowly improves over months. Patients taking ethambutol should have baseline eye tests performed and should contact their physician promptly if symptoms of blurry vision or other eye problems occur with discontinuation of the drug.

Gastrointestinal upset, skin rash or irritations, fever, and muscle aches are rare.

Ethambutol is a pill taken by mouth according to the patient’s weight in kilograms and given at 15 mg/kg daily or 25 mg/kg three times weekly.

Streptomycin (Strep)

Streptomycin is not absorbed by mouth and must be given by injection. The main side effects with streptomycin are problems with balance and auditory (ears) toxicity. Patients taking streptomycin should be instructed to be aware of decreased hearing, roaring or cricket-like sounds in the ears (called tinnitus), and problems with balance, numbness or tingling, fever and headache and notify their physician if any reaction occurs. Kidney damage may also occur, as well as changes in blood counts, so these should be routinely monitored while on this drug.

Streptomycin is given by intramuscular injection and the dosages are based on body weight, age, and physical condition of the patient. Although not approved for IV use, the drug can safely be administered by this method when needed usually via a peripherally inserted central catheter (called a PICC line for short).

Generally, streptomycin is given 2 to 3 times per week but may be given as often as daily in younger patients. The average dosage is 500 mg per injection in adults. The drug is not readily available in all pharmacies. It is generally given to patients with severe or extensive disease, or those who have failed the standard three drug regimen.

Amikacin

Amikacin is an aminoglycoside similar to streptomycin. It is not absorbed by mouth. Common side effects from taking amikacin are similar to streptomycin and include sounds in the ear (tinnitus), hearing loss, poor balance, and kidney damage/failure. Rash is rare. Amikacin is an alternative injectable agent but tends to be more toxic and is more expensive than streptomycin. The usual adult dose is 500 mg given two to five times per week.

Recently inhaled (aerosolized) amikacin has been used as a companion drug for patients with MAC, especially for patients who have failed the standard treatment. Average dosage is 250 mg 2 to 4 times weekly for 6 months.

DRUGS FOR PATIENTS WHO FAIL INITIAL THERAPY

Clofazimine (Lamprene)

Clofazimine has been used in the past primarily for treatment of leprosy (Mycobacterium leprae). However, it is sometimes used to treat patients with MAC, especially with drug resistant strains of MAC or patients who have failed standard therapy.

Gastrointestinal upset including loss of appetite (anorexia), diarrhea, and abdominal pain are the most common side effect. Dry mouth and skin may occur and because clofazimine is a dye, red-brown to nearly black skin pigmentation is a common result of drug accumulation. The usual adult dose is 100 mg to 200 mg by mouth daily.

The drug is not commercially available, and requires special application to the FDA to get approval for its use (as of 2005). This issue is well discussed at the NTM website http://www.ntminfo.com.

Quinolones

Quinolone antibiotics such as ciprofloxacin, levofloxacin (levaquin), gatifloxacin (tequin), and moxifloxacin (avelox), are sometimes used in the treatment of MAC although their effectiveness is less than optimal and the patient should be instructed not to take a quinolone alone or with only zithromax or biaxin. Side effects include dizziness, diarrhea, nausea, and anorexia are not uncommon. Their efficacy is not widely known in the treatment of MAC.
These antibiotics are generally given in pill form at the manufacturer’s recommended adult dose that ranges from 400-750 mg daily.

Rifabutin

In patients who take rifampin initially and do not convert their sputum to negative, rifabutin is considered as a replacement for rifampin. (See previous information under standard drugs.)