Department of Microbiology

For The Patient


FOR THE PATIENT: What is MAC (Mycobacterium avium complex) and How is it Diagnosed and Treated?
Barbara A. Brown-Elliott, MS, MT(ASCP)SM
Supervisor, Mycobacteria/Nocardia Laboratory Research Assistant Professor, Microbiology Coordinator, Mycobacterial Clinical Trials

Germs, like plants and animals, are grouped into "families." One such family is called Mycobacteria . This family of germs is divided into smaller groups called species, many of which can cause human disease. The most commonly recognized species is Mycobacterium tuberculosis which causes a contagious lung disease in humans called tuberculosis. This disease is spread by person-to-person contact by coughing.

You have been diagnosed with a lung disease caused by a related germ called Mycobacterium avium complex. We refer to that germ as MAC. The difference between your germ and the germ that causes tuberculosis is that your germ is not spread by person to person contact and is not considered to be contagious. MAC infection is acquired from the environment. We do not know how or why people become infected with this MAC germ. Although we can easily recover the germ from soil, water, and air samples, most people do not become sick from this organism (fewer than one in 10,000). Scientists and physicians who study these germs, think that perhaps the people who become infected have some defect in the structure or function of their lungs or in their immune systems. People who have damaged lung tissue from previous tuberculosis, heavy smoking, and a breathing tube disease called bronchiectasis, are three recognized risk factors which make you more likely to develop this disease. Disease in men most commonly relates to heavy smoking, while disease in women most commonly relates to bronchiectasis. Together with other related mycobacteria which also are not contagious, MAC is a member of a group of germs called nontuberculous mycobacteria (or NTM).

The most common NTM germs involved in human infection are Mycobacterium avium complex (MAC), M. kansasii, M. chelonae, and M. abscessus . These germs can also cause disease in the skin (usually following local injury), but the most common organ affected is the lung. Diagnosis of these infections usually depends on growing the germ from coughed up lung samples (sputum). For a diagnosis of MAC lung infection to be made, the following tests or evaluations are usually performed:

  • Medical history with a recording of your symptoms. (Such as cough, weight loss, sputum production, fatigue, fever, night sweats, etc.)
  • Chest x-ray. (Makes a picture of your lungs internally to diagnosis disease or infections.)
  • CAT scan - a type of x-ray that shows the lung in greater deatail than a plain chest x-ray
  • Sputum culture - several sputum cultures are usually performed. Your specimen coughed up from your lungs is examined under a microscope and put on special media to grow the germs.
  • Sometimes more complicated laboratory diagnostic procedures may be necessary to properly diagnose NTM, such as putting a tube down into your lungs (this procedure is called a bronchoscopy).

Our hospital and research laboratory at the UT Health Northeast has been working for more than 15 years with the Food and Drug Administration (FDA) and several pharmaceutical companies (who make drugs called antibiotics which fight against these germs) to find ways to better treat these NTM infections, especially MAC. Most of the NTM are resistant to the ordinary antibiotics which are used to treat them, and many treatments in the past have failed. A combination of several new recently available drugs combined with some TB drugs has recently been used successfully to treat these NTM infections, including MAC. You may have been sent here by your local physician or health department because of our expertise in treating MAC and the good results of our treatment protocols with these new drugs. The combination and doses of drugs given to you will be based upon your clinical history, age, weight, and symptoms and the results of your chest x-ray and sputum cultures. It is important for you to know that you are not a "guinea pig" in a scientific experiment. These drugs which we can offer you are FDA approved and available through your local doctor. That means that the FDA says that the drugs are safe to use; it is just that we need better information about the amount of each drug that needs to be given, how often they need to be given, and how long they need to be given to decide which treatment regimen has the greatest benefit with the least amount of side effects. "Treatment trials" involve the use of these FDA approved drugs, but with all patients in the trial receiving the same drugs at the same doses at the same frequency. More than 300 patients have been involved in these trials over the past 15 years. Current standard treatment of MAC lung infection involves three drugs (biaxin, ethambutol, and rifampin) taken three times a week fora minimum of 15-18 months. Because many of these drugs have side effects, you should be monitored carefully while you are taking the drugs. Monthly labs tests to check liver function, eye checks, and sputum cultures will all be necessary while you are on the medicines. The NTM usually grow slowly in the body and may take years for your disease to be recognized, but treatment is essential in controlling and curing the diseases caused by NTM.

MAC Facts

What is MAC (Mycobacterium avium complex) and How is it Diagnosed and Treated?

* Formerly known as “atypical mycobacteria”, “atypical TB”, or “atypical AFB” and currently as “nontuberculous mycobacteria” or “NTM”

* Related to Mycobacterium tuberculosis (Mtb) but it is not TB.

* NTM includes a number of different species, but the most common one causing disease is MAC.

* MAC is not spread person to person like Mtb. MAC is not contagious.

* MAC lung disease seen in HIV (-) (non-AIDS) patients is a chronic lung infection and early-on is often misdiagnosed as chronic bronchitis or recurrent pneumonia.

* MAC infection is often acquired from the environment (soil, air, natural waters, tap water, etc.)

* Scientists and physicians who have studied MAC believe people become infected because of a defect in the structure or function of their lungs (especially a disease called bronchiectasis) or in their immune systems.

* Damaged lung tissue can result from previous TB, heavy smoking, and a breathing tube disease called bronchiectasis.

* Bronchiectasis is a breathing tube (bronchial) disorder characterized by excessive mucus production, cough, and susceptibility to certain infections such as MAC or infection caused by the bacteria Pseudomonas aeruginosa.

* Disease in men commonly relates to smoking while disease in women (non-smoking) usually relates to bronchiectasis.

* The average age of patients with MAC lung disease in men is approximately 55 years and approximately 67 years in women.

* Men are more likely to have cavitary MAC (holes in their lungs).
Women are more likely to have non-cavitary, nodular MAC.

* Diagnosis of MAC usually requires:

• Medical history with records of symptoms:

Cough Fever
Weight loss Fatigue
Sputum production Night sweats

• Chest x-ray (a picture of your lungs internally)

• High resolution CAT scan (similar to an x-ray but a more detailed picture)

• Sputum culture - several sputum cultures are usually performed. Your specimen coughed from your lungs is examined under a microscope (AFB smear) and also placed on special media to grow mycobacteria (AFB culture).

• Bronchoscopy - may be necessary in some cases (especially if you can not cough up sputum) but not all, and involves putting a tube down into your lungs to obtain specimens for culture.

* Treatment of MAC requires a multi-drug regimen (more than one drug).

• MAC is resistant to ordinary antibiotics.

• Combination of 3 drugs (all FDA approved)/dosages are based upon your clinical history, age, weight, and symptoms.

Clarithromycin (Biaxin) or Azithromycin (Zithromax)
Rifampin (Rifadin) or Rifabutin (Mycobutin)
Ethambutol (Myambutol)

• The combination of medicines is given until no more MAC germs can be grown by culture of your sputum for 1 year. Average treatment period is about 15-18 months.

• Monthly sputum cultures are performed while you are on therapy and periodically when you finish your therapy to be sure your MAC is gone.

• The 3-drug regimen is given 3 times weekly (preferably Monday-Wednesday-Friday)

• Data from previous treatment trials tells us that most patients (approximately 80%) who can tolerate the appropriate medicines will get better and may be “cured”.

• Patients who take the 3-drug regimen for less than 1 year with negative cultures are more likely to develop another infection or relapse with disease.

• Patients who fail therapy after taking the 3 medicines are usually required to take additional medicines (injectables) which may be useful.

Streptomycin/ Amikacin

• Monthly laboratory tests to check kidneys and liver along with complete blood count (CBC) are necessary while you are taking the medicines.

* Most common potential side effects/complications of medicines:

Clarithromycin : Loss of appetite, diarrhea, nausea, abdominal pain, abnormal liver function tests (blood tests), bitter taste, mild allergic rash.

Azithromycin : Diarrhea, nausea, abdominal pain, abnormal liver function tests (blood tests), decreased hearing, tinnitus (sounds in ears).

Rifampin : Nausea, vomiting, liver damage, decreased platelets (cells which clot blood), body secretions are orange/red.

Rifabutin : Nausea, vomiting, decreased platelets (cells which clot blood), decreased white blood cells (cells which fight infection), eye pain, diffuse muscle and joint aches, skin pigmentation (orange).

Ethambutol : Decrease in vision (especially color vision), blurriness.

Streptomycin : Kidney damage, sounds in ears (tinnitus), hearing loss, poor balance, numbness, tingling, muscle damage, fever, headache.

Amikacin : Kidney damage, hearing loss, poor balance, muscle damage, fever, headache, numbness.

If you experience these or other additional problems, you should discuss them with your physician.

Additionally, you should provide a list of your current medicines to your physician so he can determine any possible contra-indications.

* UT Health Northeast MAC clinic and research team is led by Dr. Richard J. Wallace Jr., an infectious disease physician and microbiologist with more than 40 years experience in mycobacterial infections. He has authored approximately 300 scientific papers, most of these about NTM. He has also received numerous awards for his work with mycobacteri. He is joined by pulmonologist Dr. David Griffith who has extensive experience in mycobacterial lung disease, and Barbara Brown-Elliott, MS, MT(ASCP)SM, laboratory supervisor and clinical trials coordinator for mycobacterial studies with more than 30 years experience in laboratory medicine, including 21 years in mycobacterial research. Dr. Wallace and Barbara have been honored to receive the Gardner Middlebrook Award for significant contributions in mycobacteriology. This is an annual award given at the international General Meeting of the American Society for Microbiology each year.

REFERENCES

  1. Wolinsky E: Nontuberculous mycobacteria and associated diseases. Am. Rev. Respir. Dis. 119:107-159, 1979.
  2. Wallace RJ Jr, Cook JL, Glassroth J, Raleigh J, Dutt A: Diagnosis and treatment of disease caused by nontuberculous mycobacteria, NTM Statement, American Thoracic Society. Am. Rev. Respir. Dis. 142:940-953, 1990 .
  3. Brown BA, Wallace RJ Jr, Onyi G: Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system. Antimicrob. Agents Chemother . 36: 1987-1990, 1992 .
  4. Wallace RJ Jr, Brown BA, Griffith DE: Drug intolerance to high dose clarithromycin among elderly patients. Diagn. Microbiol. Infect. Dis. 16:215-221, 1993 .
  5. Wallace RJ Jr: Mycobacterium avium complex lung disease and women. Now an equal opportunity disease. Chest , 105:6-7, 1994
  6. Meier A, Kirschner P, Burkhardt S, Steingrube VA, Brown BA, Wallace RJ Jr, Böttger E: Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare. Antimicrob. Agents Chemother. 38:381-384, 1994 .
  7. Wallace RJ Jr, Brown BA, Griffith DE, Girard WM, Murphy DT, Onyi GO, Steingrube VA, Mazurek GH: Initial clarithromycin monotherapy for Mycobacterium avium-intracellulare complex lung disease. Amer. Rev. Resp. Dis. 149:1335-134, 1994 .
  8. Griffith DE, Brown BA, Girard WM, Wallace RJ Jr: Adverse events associated with high-dose rifabutin in macrolide-containing regimens for the treatment of Mycobacterium avium complex lung disease. Clin. Infect. Dis. 21-594-598, 1995.
  9. Wallace RJ Jr, Brown BA, Griffth DE, Girard W, Tanaka K: Reduced serum levels of clarithromycin in patients with multidrug regimens including rifampin or rifabutin for Mycobacterium avium-M. intracellulare infection. J. Infect. Dis. 171-747-750, 1995
  10. .Wallace RJ Jr, Brown BA, Griffith DE, Girard W. Tanaka K: Reduced serum levels of clarithromycin in patients with multidrug regimens including rifampin or rifabutin for Mycobacterium avium-M. intracellulare infection. J. Infect. Dis. 171-747-750, 1995 .
  11. Brown, BA, Wallace RJ Jr, Griffith DE, Girard W: Clarithromycin-induced hepatotoxicity. Clin. Infect. Dis. 20-173-174, 1995 .
  12. Inderlied CB, Salfinger M: Antimicrobial agents and susceptibility tests: Mycobacteria. In: Manual of Clinical Microbiology, 6th ed., Patrick R. Murray, editor, ASM Press, Washington, D.C. 1995 ; 119-1385-1402.
  13. Griffith DE, Brown BA, Girard WM, Murphy DT, Wallace RJ Jr: Azithromycin activity against Mycobacterium avium complex lung disease in patients who were not infected with human immunodeficiency virus. Clin. Infect. Dis. 23:983-989, 1996 .
  14. Griffith DE, Brown BA, Wallace RJ Jr: Varying dosages of rifabutin affect white blood cell and platelet counts in human immunodeficiency virus-negative patients who are receiving multidrug regimens for pulmonary Mycobacterium avium complex disease. Clin. Infect. Dis. 23:1321-1322, 1996
  15. Meier A, Heifets L, Wallace RJ Jr., Zhang Y, Brown BA, Sander P, Böttger EC: Molecular mechanisms of clarithromycin resistance in Mycobacterium avium : observation of multiple 23S rDNA mutations in a clonal population. J. Infect. Dis. 174-354-360, 1996.
  16. Wallace RJ Jr, Brown BA, Griffith DE, Girard WM, Murphy DT: Clarithromycin regimens for pulmonary Mycobacterium avium complex - the first 50 patients. Am. J. Respir. Crit. Care Med. 153:1766-1772, 1996.
  17. Meier A, Heifets L, Wallace RJ Jr., Zhang Y, Brown BA, Sander P, Böttger EC: Molecular mechanisms of clarithromycin resistance in Mycobacterium avium : observation of multiple 23S rDNA mutations in a clonal population. J. Infect. Dis. 174:354-360, 1996 .
  18. Wallace RJ Jr., Cook JL, Glassroth J, Griffith DE, Olivier KN, Gordin F: American Thoracic Society Statement: Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am. Respir. Crit. Care Med. 156:S1-S25, 1997.
  19. Brown BA, Wallace RJ Jr., Griffith DE, Warden R: Clarithromycin-associated digoxin toxicity in the elderly. Clin. Infect. Dis. 24:92-93, 1997 .
  20. Brown BA, Griffith DE, Girard W, Levin J, Wallace RJ Jr: Relationship of adverse events to serum drug levels in patients receiving high-dose azithromycin for mycobacterial lung disease. Clin. Infect. Dis. 24-958-964, 1997 .
  21. Griffith DE, Wallace RJ Jr: Treatment of pulmonary Mycobacterium avium complex lung disease in non-acquired immunodeficiency syndrome (AIDS) patients in the era of newer macrolides and rifabutin. Am. J. Med. 102-22-27, 1997.
  22. Griffith DE, Brown BA, Murphy DT, Girard WM, Couch L, Wallace RJ Jr: Initial (6 months) results of three-times-weekly azithromycin in treatment regimens for Mycobacterium avium complex lung disease in human immunodeficiency virus-negative patients. J. Infect. Dis. 178-121-126, 1998 .
  23. Nelson KG, Griffith DE, Brown BA, Wallace RJ Jr: Results of operation in Mycobacterium avium-intracellulare lung disease. Ann. Thorac. Surg. 66:325-330, 1998.
  24. Wallace RJ Jr, Zhang Y, Brown BA, Dawson D, Murphy DT, Wilson R, Griffith DE: Polyclonal Mycobacterium avium complex infections in patients with nodular bronchiectasis. Am. J. Respir. Crit. Care Med. 158:1235-1244, 1998 .
  25. Huang JH, Kao PN, Adi V, Ruoss SJ: Mycobacterium avium-intracellulare pulmonary infection in HIV-negative patients without preexisting lung disease. Chest 1033-1040, 1999.
  26. Griffith DE, Brown BA, Cegielski P, Murphy DT, Wallace RJ Jr: Early results (at 6 months) with intermittent clarithromycin-including regimens for lung disease due to Mycobacterium avium complex. Clin. Infect. Dis. 30-288-292, 2000
  27. Wallace RJ Jr: Antimycobacterial agents. In: Mandel, Douglas and Bennett’s Principles and Practice of Infectious Diseases , Fifth edition, Mandell, Bennett, Dolin, eds. Churchill Livingston Inc., Vol. 1, 34-436-448, 2000 .
  28. Griffith DE, Brown BA, Girard WM, Griffith BE, Couch LA, Wallace RJ Jr: Azithromycin-containing regimens for treatment of Mycobacterium avium complex lung disease. Clin. Infect. Dis. 32:1547-1553, 2001.
  29. Wallace RJ Jr, Brown-Elliott BA, Griffith DE: Nontuberculous mycobacteria. In: Respiratory Infections , Second Edition, MS Niederman, GA Sarosi, J. Glassroth eds. Lippincott Williams & Wilkins, Philadelphia. 38:487-500, 2001 .
  30. Griffith DE, Brown-Elliott BA, Wallace RJ Jr: Diagnosis of nontuberculous mycobacterial lung disease. Infect. Dis. Clin. North Am. 16:235-249, 2002.
  31. Wallace RJ Jr, Zhang Y, Brown-Elliott BA, Yakrus MA, Wilson RW, Mann L, Couch L, Girard WM, Griffith DE: Repeat positive cultures in Mycobacterium intracellulare lung disease after macrolide therapy represent new infections in patients with nodular bronchiectasis. J. Infect. Dis. 186:266-273, 2002.
  32. Brown-Elliott BA, Grffith DE, Wallace RJ Jr: Diagnosis of nontuberculous mycobacterial infections. Clin. Lab. Med. 22:911-925, 2002 .
  33. Wallace JR Jr, Zhang Y, Brown-Elliott BA, Yakrus MA, Wilson RW, Mann L, Couch L, Girard WM, Griffith De: Repeat positive cultures in Mycobacterium intracellulare lung disase after macrolide therapy represent new infections in patients with nodular bronchiectasis. J. Infect. Dis. 186:266-273, 2002 .
  34. Woods GL, Williams-Bouyer N, Wallace RJ Jr, Brown-Elliott, BA, Witebsky FG, Conville PS, Plaunt M, Hall G, Arala P, Inderlied C: Multisite reproducibility of results obtained by two broth dilution methods for susceptibility testing of Mycobacterium avium complex. J. Clin. Microbiol. , 41:627-631, 2003 .
  35. Olivier KN, Weber DJ, Wallace RJ Jr., Faiz AR, Lee J, Zhang Y, Brown-Elliott BA, Handler A, Wilson RW, Schechter MS, Edwards LJ, Chakraborti S, Knowles MR. Nontuberculous Mycobacteria, I: Multicenter Prevalence Study in Cystic Fibrosis. Am J Respir Crit Care Med 167:828-834, 2003 .
  36. Olivier KN, Weber DJ, Lee J, Handler A, Tudor G, Molina PL, Tomashefski J, Knowles MR. Nontuberculous Mycobacteria, II: Nested-Cohort Study of Impact on Cystic Fibrosis Lung Disease. Am J Respir Crit Care Med 167:835-840, 2003 .
  37. Pfyffer GE, Brown-Elliott BA, Wallace RJ Jr: Mycobacterium : General characteristics, isolation and staining procedures. In: Manual of Clinical Microbiology, 8th edition, Patrick R. Murray, editor. ASM Press, Washington, DE, 36:532-559, 2003.
  38. Vincent V, Brown-Elliott BA, Jost KC Jr, Wallace RJ Jr: Mycobacterium : Phenotyic and genotypic identification. In Manual of Clinical Microbiology, 8th edition, Patrick R. Murray, editor. ASM Press, Washington, DC 37:560-584, 2003.
  39. Brown-Elliott BA, Crist CJ, Mann LB, Wilson RW, Wallace RJ Jr: In vitro activity of linezolid against slowly growing nontuberculous mycobacteria. Antimicrob. Agents Chemother. 47:1736-1738, 2003.
  40. Woods, GL, Brown-Elliott BA, Desmond EP, Hall GS, Heifets L, Pfyffer GE, Ridderhof JC, Wallace RJ Jr, Warren NG, Witebsky FG: Susceptibility testing of mycobacteria, nocardia, and other aerobic actinomyetes; approved standard. NCCLS, 23:M24-A, 2003.
  41. Nelson KG, Griffith D, Wallace RJ Jr: Pulmonary mycobacterial disease - the role of surgical resection. Clin. Pulm. Med. 11:35:362, 2004.
  42. Brown-Elliott BA, Wallace RJ Jr: Infectons caused by nontuberculous mycobacteria. In: Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, Sixth Edition, Mandell, Bennett, Dolin, eds, Elsevier Churchill Livingston Inc., Vol. 2, 251:2909-2916, 2005.
  43. Griffith, DE, Brown-Elliott BA, Shepherd S, McLarty J, Griffith L, Wallace RJ Jr: Ethambutol ocular toxicity in treatment regiments for Mycobacterium avium complex lung disease. Am. J. Respir. Crit. Care Med. 172:250-253, 2005.
  44. Griffith DE, Brown-Elliott BA, Langsjoen B, Zhang Y, Pan X, Girard W, Nelson K, Caccitolo J, Alvarez J, Shepherd S, Wilson R, Graviss EA, Wallace RJ Jr: Clinical and Molecular Anlaysis of Macrolide Resistance in Mycobacterium avium Complex Lung Disease. Am. J. Respir. Crit. Care Med. 174:928-934, 2006.
  45. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, Fordman von Reyn, Wallace RJ Jr, Winthrop K: An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases. Am. J. Respir. Crit. Care Med. 175:367-416, 2007.
  46. Turenne CY, Wallace RJ Jr, Behr MA: Mycobacterium avium in the postgenomic era. Clin. Microbiol. Rev. 20:205-229, 2007.
  47. Brown-Elliott, BA, Cohen, S, Wallace RJ Jr.: Susceptibility testing of mycobacteria. In: Antimicrobial Susceptibility Testing Protocols, R Schwalbe, L Steele-Moore, AC Goodwin, eds. CRC Press, Boca Raton, FL. 11:243-274, 2007.
  48. Wallace RJ Jr., Griffith DE: Antimycobacterial agents. In: Harrison’s Principles of Internal Medicine, 17th edition, AS Fauci, DL Kasper, DL Longo, E Braunwald, SL Hauser, JL Jameson, J Loscalzo, eds. McGraw Hill. 161:1032-1038, 2008.
  49. Forbes BA, Banaiee N, Beavis KG, Brown-Elliott BA, Della Latta P, Elliott LB, Hall GS, Hanna B, Perkins MD, Siddiqi SH, Wallace RJ Jr, Warren NG: Laboratory detection and identification of mycobacteria; Approved guideline. Clinical and Laboratory Standards Institute, M48-A, 2008.
  50. Brown-Elliott BA, Wallace RJ Jr: Infections due to nontuberculous mycobacteria other than Mycobacterium avium-intracellulare. In: Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, Seventh Edition, Mandell, Bennett, Dolin, eds, Elsevier Churchill Livingstone Inc., Vol. 2, 253: 3191-3198, 2010.
  51. Babady NE, Hall L, Abbenyi AT, Eisberner JJ, Brown-Elliott BA, Pratt CJ, McGlasson MC, Beirle DK, Wohlfiel SL, Deml SM, Wallace RJ Jr, Wengenack NL: Evaluation of Mycobacterium avium complex clarithromycin susceptibility testing using SLOMYCO sensititre panels and JustOne strips. J. Clin. Microbiol. 48:1749-1752, 2010.
  52. Wallace RJ Jr., Griffith DE: Antimycobacterial agents. In: Harrison’s Infectious Diseases, DL Kasper, AS Fauci, eds. McGraw Hill. 69:635-643, 2010.
  53. Richter E, Brown-Elliott BA, Wallace RJ Jr.: Mycobacterium: Laboratory characteristics of slowly growing mycobacteria. In: Manual of Clinical Microbiology, 9th Edition, P.R. Murray, ed. ASM Press, Washington, D.C. Vol. 1, pp. 503-524, 2010.

If desired, donations to the MAC research fund can be sent to the UT Health Northeast and checks marked for "MAC Research Fund, Account #421401". Thank you for your interest and support of our research efforts.

For additional information, please visit our website at maclungdisease.org

Rapidly Growing Mycobacterial Lung Disease (M. chelonae/M. abscessus and M. fortuitum group)
Although early studies identified most respiratory isolates of rapidly growing mycobacteria (RGM) as Mycobacterium fortuitum, use of modern identification schemes have shown that Mycobacterium abscessus (formerly M. chelonae subspecies abscessus) accounts for approximately 80% of RGM respiratory disease isolates while M. fortuitum (formerly M. fortuitum biovariant fortuitum) accounts for approximately 15% of these isolates. An important exception is the small group of patients with gastroesophageal disorders with chronic vomiting and RGM lung disease in whom M. abscessus and M. fortuitum occur with equal frequency. Overall, M. abscessus appears to be a more virulent respiratory pathogen than M. fortuitum. Many laboratories do not separate M. abscessus from the closely related M. chelonae so many respiratory isolates will be incorrectly referred to as "M. chelonae." Obtaining a single respiratory isolate of M. abscessus is more likely to indicate significant disease than a single isolate of M. fortuitum, although careful clinical evaluation and follow-up is always necessary to determine the significance of NTM respiratory isolates especially in a single sputum sample.

M. fortuitum isolates, when they do occur, are usually susceptible to multiple oral antimicrobial agents including the quinolones, doxycycline and minocycline, sulfonamides (including trimethoprim/sulfa) and linezolid. Drug susceptibilities for this species are essential for effective therapy. New research inicates the presence of a gene in some species of the M. fortuitum group that renders it clinically (in vivo) resistant to macrolides while it may appear susceptible by laboratory MIC testing (in vitro) as susceptible. Six to 12 months of therapy with two or more of these oral antimicrobials, often preceded by 2 to 6 weeks of IV therapy that includes amikacin, usually results in clinical cure.

M. abscessus isolates are usually susceptible on laboratory evaluation only to the injectable agents amikacin, cefoxitin and imipenem and to the newer oral macrolides, clarithromycin and azithromycin. About 50% of the isolates of M. abscessus have MICs for the newer antibiotic, linezolid, in the intermediate or susceptible range (< 16 µg/mL), suggesting this drug may be useful for some patients. Preliminary studies suggest that monotherapy with the newer macrolides (clarithromycin or azithromycin) is not sufficient to produce microbiologic cure for M. abscessus.

Recent studies have shown that M. abscessus is composed of at least two subspecies: M. abscessus subsp. abscessus and M. abscessus subsp. bolletii. Although isolates of M. abscessus subsp. abscessus have susceptible MICs to macrolides at routine incubation of 3 days, most isolates of M. abscessus subsp. abscessus have resistant MICs after extended incubation, the result of an erythromycin methylase gene (erm 41) which induces macrolide resistance. However a 2010 study showed that patients with M. abscessus subsp. bolletii (formerly including M. massiliense) and not containing a functional erm gene had a higher response rate (90%) than patients with M. abscessus subsp. abscessus (25%). M. abscessus subsp. bolletii does not appear to contain a functional erm gene.

Combination therapy of low dose intravenous amikacin (average 400 mg twice daily for peaks 20-25 µg/mL range) plus high dose cefoxitin up to 12 grams/day) or imipenem for 2 to 4 weeks almost invariably produces clinical and microbiologic improvement, but cost and morbidity prohibit potentially curative courses of treatment (probably 4 to 6 months). Linezolid may also be effective in some cases but susceptibility testing should be performed and there is no published data on the results of therapy for M. abscessus. The exorbitant cost of this medicine ($100.00/day) has precluded all efforts to date at a clinical trial. Imipenem appears as effective as cefoxitin for isolates of M. abscessus. Routine monitoring of renal function, eighth nerve function and white blood cell counts (for beta lactams) should be performed on patients receiving these regimens. Patients on linezolid are generally treated with 600 mg once daily to try to minimize cost and toxicity, with careful long term monitoring of hematologic parameters. Surgical resection for localized lung disease can also be curative. Unfortunately, symptomatic care, including periodic parenteral antibiotic and/or oral macrolide therapy, may be all that can be realistically administered to control the symptoms and progression of most patients with bilateral M. abscessus lung disease.

A new parenteral antibiotic, tigecycline (formerly GAR-936), is a derivative of minocycline and has exciting therapeutic potential for treatment of diseases caused by the RGM, especially M. chelonae and M. abscessus. The antibiotic has recently been approved by the FDA. In vitro susceptibility studies have shown most isolates of M. abscessus to have MICs to tigecycline < 1 μg/ml.

Surgery may be an option in some cases but should be carefully reviewed with a specialist in the treatment of M. abscessus lung disease.

Respiratory infections with other mycobacterial species may also occur but are less commonly seen than the M. abscessus group.

REFERENCES

  1. Swenson JM, Wallace RJ Jr., Silcox VA, Thornsberry C: Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae Antimicrob. Agents Chemother. 28:807-811, 1985.
  2. Kusunoki S, Ezaki T: Proposal of Mycobacterium peregrinum sp. nov., nom. rev., and elevation of Mycobacterium chelonae subsp. abscessus (Kubica et al.) to species status: Mycobacterium abscessus comb. nov. Int. J. Syst. Bacteriol . 42:240-245, 1992.
  3. Brown BA, Wallace RJ Jr., Onyi GO, De Rosas V, Wallace RJ III: Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum,
    Mycobacterium chelonae , and M. chelonae -like organisms. Antimicrob. Agents Chemother. 36:180-184, 1992.
  4. Griffith DE, Girard WM, Wallace, RJ Jr: Clinical features of pulmonary disease caused by rapidly growing mycobacteria: An analysis of 154 patients. Am. Rev. Respir. Dis., 147:1271-1278, 1993.
  5. Wallace RJ Jr., Silcox V, Brown BA: Taxonomy of rapidly growing growing mycobacteria. Clin. Infect. Dis. 18:121-122, 1994.
  6. Brown BA, Wallace RJ, Onyi GO: Activities of the glycylcyclines N, N-dimethylglycylamido-minocycline and N, N-dimethylglycylamido-6-demethyl-6-deoxytetracycline against Nocardia spp. and tetracycline-resistant isolates of rapidly growing mycobacteria. Antimicrob. Agents Chemother. 40:874-878, 1996 .
  7. Wallace RJ Jr, Meier A, Brown BA, Zhang Y, Sander P, Onyi GO, Böttger EC: Genetic basis for clarithromycin resistance among isolates of Mycobacterium chelonae and Mycobacterium abscessus . Antimicrob. Agents Chemother. 40:1676-1681, 1996 .
  8. Prammananan T, Sander P, Brown BA, Frischkorn K, Onyi GO, Zhang Y, Böttger EC, Wallace RJ Jr: A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae . J. Infect. Dis. 177:1573-1581, 1998 .
  9. Wallace RJ Jr, Brown BA: Mycobacterium fortuitum, chelonae, abscessus . In: Tuberculosis and Nontuberculous Mycobacterial Infections , David Schlossberg, ed., W.B. Saunders Co., p. 372-379, 1999 .
  10. Wallace RJ Jr, Brown-Elliott BA, Ward SC, Crist CJ, Mann LB, Wilson RW: Activities of linezolid against rapidly growing mycobacteria. Antimicrob. Agents Chemother. 45:764-767, 2001.
  11. Bange F-C, Brown BA, Smaczny C, Wallace RJ Jr, Böttger EC: Lack of transmission of Mycobacterium abscessus among patients with cystic fibrosis attending a single clinic. Clin. Infect. Dis. 32: 1648-1650, 2001 .
  12. Wallace RJ Jr., Brown-Elliott BA, Crist CJ, Mann LB, Wilson RW: Comparison of the in vitro activity of the glycylcycline, tigecycline (formerly GAR-936), with tetracycline, minocycline, and doxycycline against isolates of nontuberculous mycobacteria. Antimicrob. Agents and Chemother. , 46:3164-3167, 2002 .
  13. Brown-Elliott BA, Wallace RJ Jr, Crist CJ, Mann L, Wilson RW: Comparison of in vitro activities of gatifloxacin and ciprofloxacin against four taxa of rapidly growing mycobacteria. Antimicrob. Agents Chemother. 46:3283-3284, 2002 .
  14. Brown-Elliott BA, Wallace RJ Jr: Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin. Microbiol. Rev . 15:716-746, 2002 .
  15. Olivier KN, Weber DJ, Wallace RJ Jr., Faiz AR, Lee J, Zhang Y, Brown-Elliott BA, Handler A, Wilson RW, Schechter MS, Edwards LJ, Chakraborti S, Knowles MR. Nontuberculous Mycobacteria, I: Multicenter Prevalence Study in Cystic Fibrosis. Am J Respir Crit Care Med 167:828-834, 2003 .
  16. Olivier KN, Weber DJ, Lee J, Handler A, Tudor G, Molina PL, Tomashefski J, Knowles MR. Nontuberculous Mycobacteria, II: Nested-Cohort Study of Impact on Cystic Fibrosis Lung Disease. Am J Respir Crit Care Med 167:835-840, 2003.
  17. Wallace RJ Jr, Brown-Elliott BA, Wilson RW, Mann L, Hall L, Zhang Y, Jost KC Jr, Brown JM, Kabani A, Schinsky MF, Steigerwalt AG, Crist CJ, Roberts GD, Blacklock Z, Tsukamura M, Silcox V, Turenne C: Clinical and laboratory features of Mycobacterium porcinum. J. Clin. Microbiol. 42:5689-5697, 2004.
  18. Zhang Y, Yakrus MA, Graviss EA, Williams-Bouyer N, Turenne C, Kabani A, Wallace RJ Jr: Pulsed-field gel electrophoresis study of Mycobacterium abscessus isolates previously affected by DNA degradation. J. Clin. Microbiol. 42:5582-5587, 2004.
  19. Brown-Elliott BA, Wallace RJ Jr: Infections caused by nontuberculous mycobacteria. In: Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, Sixth Ediction, Mandell, Bennett, Dolin, eds, Elsevier Churchill Livingstone Inc. Vol. 2, 251:2909-2916, 2005.
  20. Wallace RJ Jr, Brown-Elliott BA, Brown J, Steigerwalt AG, Hall L, Woods G, Cloud J, Mann L, Wilson R, Crist C, Jost KC Jr, Byrer DE, Tang J, Cooper J, Stamenova E, Campbell B, Wolfe J, Turenne C: Polyphasic characterization reveals that the human pathogen Mycobacterium peregrinum type II belongs to the bovine pathogen species Mycobacterium senegalense. J. Clin Microbiol. 43:5925-5935, 2005.
  21. Nash KA, Zhang Y, Brown-Elliott BA, Wallace RJ Jr: Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J. Antimicrob. Chemother. 2005; 55:17-177.
  22. Brown-Elliott BA, Wallace RJ Jr: Rapidly growing mycobacteria. In: Tuberculosis & Nontuberculous Mycobacterial Infections, 5th edition, D Schlossberg, ed. McGraw-Hill Companies, Inc., 356:451-462, 2006.
  23. Nash KA, Andini N, Zhang Y, Brown-Elliott BA, Wallace RJ Jr. Intrinisic Macrolide Resistance in Rapidly Growing Mycobacteria. Antimicro. Agents & Chemo. . 50:3476-3478, 2006.
  24. Griffith DE, Aksamit T, Brown-Elliott BA, et. al. An Official ATS/IDSA Statement: Diagnosis, Treatment and Prevention of Nontuberculous Mycobacterial Diseases. Am. J. Respir. Crit. Care Med. 175:367-416, 2007.
  25. Nash, K. A., B. A. Brown-Elliott, and R. J. Wallace Jr. A novel gene, erm(41), confers inducible macrolide resistance to clinical isolates of Mycobacterium abscessus but is absent from Mycobacterium chelonae. Antimicrob. Agents Chemother. 53:1367-1376, 2009.
  26. Zelazny AM, Root JM, Shea YR, Colombo RE, Shamputa IC, Stock F, Conlan S, McNulty S, Brown-Elliott BA, Wallace RJ Jr., Oliver KN, Holland SM, Sampaio EP: Cohort study of molecular identification and typing of Mycobacterium abscessus, Mycobacterium massiliense, and Mycobacterium bolletii. J. Clin. Microbiol. 47:1985-1995, 2009.
  27. Metersky ML, Bean SC, Meyer JD, Mutambudzi M, Brown-Elliott BA, Wechsler ME, Wallace RJ Jr: Trombone player’s lung. Chest., 138:754-755, 2010.
    Brown-Elliott BA, Wallace RJ Jr., Petti CA, Mann LB, McGlasson M, Chihara S, Smith GL, Painter P, Hail D, Wilson R, Simmon KE: Mycobacterium neoaurum and Mycobacterium bacteremicum sp. nov. as causes of mycobacteremia. J. Clin. Microbiol. , 48:4377-4385, 2010.
  28. Brown-Elliott BA, Wallace RJ Jr: Rapidly growing mycobacteria. In: Tuberculosis & Nontuberculous Mycobacterial Infections, 6th edition, D Schlossberg, ed. McGraw-Hill Companies, Inc., Accepted, 2010.
  29. Brown-Elliott BA, Wallace RJ Jr.: Mycobacterium: Clinical and Laboratory Characteristics of rapidly growing mycobacteria. In: Manual of Clinical Microbiology, 10th Edition, P.R. Murray, ed. ASM Press, Washington, D.C., Vol. 1, pp. 525-538, 2011.
  30. Huth RG, Brown-Elliott BA, Wallace RJ Jr: Mycobacterium mageritense pulmonary disease in an immunocompromised host. Letter to the Editor. Emerg. Infect. Dis. , 17: 556-558, 2011.
  31. Koh W. Jeon K, Lee NY, Kim B, Kook Y, Lee S, Park YK, Kim CK, Stin SJ, Huitt GA, Daley CL, Kwon OJ. Clinical Significance of Differentiation of Mycobacterium massiliense from Mycobacterium abscessus. Am. J. Respi. Crit. Care Med. 183: 405-410. 2011.

Last Update: July 26, 2011.

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