Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Mycobacterium Avium-Intracellulare Treatment & Management

  • Author: Janak Koirala, MD, MPH, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Oct 06, 2015
 

Approach Considerations

Mycobacteriumavium complex (MAC) is intrinsically resistant to many antibiotics and antituberculosis drugs but is fairly susceptible to the following agents:

  • Macrolides (eg, clarithromycin, azithromycin)
  • Rifamycins (eg, rifampin, rifabutin)
  • Ethambutol
  • Clofazimine
  • Fluoroquinolones (eg, ciprofloxacin, levofloxacin, moxifloxacin)
  • Aminoglycosides (eg, amikacin, streptomycin)

In general, MAC infection is treated with 2 or 3 antimicrobials for at least 12 months. Commonly used first-line drugs include macrolides (clarithromycin or azithromycin), ethambutol, and rifamycins (rifampin, rifabutin). Aminoglycosides, such as streptomycin and amikacin, are also used as additional agents.[19]

Aerosolized amikacin has been found to be an effective adjunctive therapy in a small case series.[20] Fluoroquinolones (levofloxacin, moxifloxacin) and clofazimine should be used as second-line agents against MAC because of the poor outcome associated with them compared with macrolide-containing regimens. Linezolid and ketolides also demonstrate good in vitro activity against MAC and other mycobacteria, although clinical data to support their use are lacking.

MAC lymphadenitis in children is treated with surgical excision of the affected lymph nodes. Antibiotics are generally not required but may be beneficial in patients with extensive lymphadenitis or with a poor response to surgical therapy.

Clinical trials have failed to show any significant clinical benefit for antimycobacterial drugs used to treat Crohn disease secondary to M aviumparatuberculosis.[21]

Pulmonary MAC infection in patients with lung disease may require surgical excision of focal pulmonary nodules. Lobectomy has also been recommended for more extensive lung infection in patients who have not responded to antibiotics in the past. This, however, does not occur as often now that more potent antibiotics are available.

The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) have issued guidelines for the diagnosis, treatment, and prevention of nontuberculous mycobacterial pulmonary infection.[18]

Next

Pulmonary MAC Infection in Immunocompetent Patients

Treatment of MAC infection in immunocompetent patients involves the combination of a newer macrolide (azithromycin or clarithromycin), ethambutol, and rifabutin.

ATS/IDSA guidelines recommend that most patients with nodular or bronchiectatic disease can be treated with a thrice-weekly regimen of clarithromycin 1000 mg or azithromycin 500 mg, rifampin 600 mg, and ethambutol 25 mg/kg. Therapy should be continued for at least one year after culture results revert to negative.[18]

Lam et al verified comparable results between daily and thrice-weekly therapy in patients with noncavitary lung disease, but found that patients with cavitary lung disease had worse outcomes with thrice-weekly therapy.[22] Therefore, patients with fibrocavitary lung disease or severe nodular or bronchiectatic disease should receive a daily regimen of clarithromycin (500–1000 mg) or azithromycin (250-500 mg) rifampin (600 mg) or rifabutin (150–300 mg), and ethambutol (15 mg/kg).

In addition, the ATS/IDSA guidelines suggest the addition of amikacin or streptomycin thrice weekly early in the course of treatment (initial 2-3 months) in patients with severe and extensive fibrocavitary lung disease.[18] Streptomycin has been used successfully in combination with macrolides for the first 6-12 weeks of treatment in patients with cavitary lung disease. In situations when rifamycins fail or cannot be taken, clofazimine has also been used with good outcome.[23]

A randomized controlled study showed comparable efficacy and tolerance when either clarithromycin or ciprofloxacin was given to patients with pulmonary MAC infection as a third drug in regimens containing rifampin and ethambutol.[24] Based on these results, it is suggested that fluoroquinolones can be used as a substitute for macrolides.

A macrolide-containing regimen has been shown to carry a cure rate of about 56%, including the dropouts and relapses in the analysis. Macrolides carry high rates of intolerance. Clarithromycin, a cytochrome P-450 inhibitor, interacts with many drugs metabolized in the liver. Similarly, rifamycins are known to induce hepatic enzymes and can alter metabolism of many drugs taken concomitantly.

A clinical study failed to verify the benefit of inhaled interferon (IFN)-gamma in patients with pulmonary MAC infection.[22] However, patients with a defect in the IFN-gamma pathways may show a better response if IFN-gamma is given in addition to the antimicrobials.

Previous
Next

Disseminated MAC Infection in Patients with AIDS

A combination of a newer macrolide antibiotic (eg, clarithromycin, azithromycin) with ethambutol and rifabutin is probably the most active regimen. Efficacies of clarithromycin and azithromycin in DMAC infection have been demonstrated in clinical studies, but monotherapy should be avoided, as it can lead to resistance. Ethambutol appears to be the best second choice to combine with a macrolide. Rifabutin should be used as a third agent.

A study comparing clarithromycin and ethambutol (dual therapy) with clarithromycin, ethambutol, and rifabutin (triple therapy) showed improved microbiological clearance and survival in the triple-therapy arm. Published data suggest 50%-60% microbiological clearance rates for both macrolides when used in combination with ethambutol and rifabutin.

Current guidelines recommend a combination of clarithromycin (500 mg twice daily) and ethambutol (15 mg/kg daily) with or without rifabutin (300 mg daily). Azithromycin (500-600 mg daily) can be substituted for clarithromycin. The addition of rifabutin has been recommended, especially in patients with advanced immunosuppression (CD4+ count < 50 cells/µL), with high mycobacterial loads (>100 colony-forming units/mL of blood), or in the absence of effective antiretroviral therapy.

Based on experience in patients without HIV infection, the guidelines suggest the use of amikacin or streptomycin as third or fourth drugs in these patients.[25]

The guidelines recommend continuing treatment until resolution of symptoms and reconstitution of cellular immunity (sustained CD4 counts >100 cells/µL).

Drug interactions are a major problem with rifabutin and clarithromycin (see Medication). Higher doses of rifabutin (≥450 mg/day) are associated with higher rates of uveitis. The usual dose of rifabutin (300 mg/day) should be reduced by half (150 mg/day) if the patient is also receiving protease inhibitors. Higher doses of clarithromycin (1000 mg bid) are associated with higher mortality rates.[25] Clofazimine use in patients with DMAC infection has been associated with a worse outcome.[26]

Fever should improve within 2-4 weeks of therapy initiation. If patients remain febrile for a longer duration than expected, repeat blood cultures and assess susceptibilities to antimicrobial agents. If the isolate is susceptible to a macrolide and the infection is not responding to therapy, consider adding other agents such as streptomycin or amikacin.

If the MAC strain is resistant to macrolides, the macrolide can be replaced with a fluoroquinolone. Although macrolide-fluoroquinolone combinations have been used to treat MAC infections in past, studies have suggested antagonism between the two classes of antibiotics in infections with some strains of MAC and higher rates of macrolide resistance among patients receiving the combination.[19]

Since patients with MAC infection who are concomitantly receiving antiretroviral therapy may develop immune reconstitution inflammatory syndrome (IRIS), the guidelines suggest withholding antiretroviral therapy during the first 2 weeks of antimycobacterial treatment. However, if the patient is already receiving antiretroviral therapy, it should be continued.

Patients with IRIS are generally treated by infectious disease specialists with nonsteroidal anti-inflammatory drugs (NSAIDS) and, if necessary, with a short course (4-8 weeks) of systemic steroids such as prednisone.[25]

Addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to be helpful in the treatment DMAC infection in patients with HIV/AIDS in whom traditional antimycobacterial therapy failed.[27]

Chemoprophylaxis

Antimycobacterial prophylaxis is recommended in HIV-infected patients with a CD4+ T-lymphocyte count under 50 cells/µL. The drug of choice is either clarithromycin 1000 mg/d or azithromycin 1200 mg/wk. In a study that compared clarithromycin prophylaxis with placebo, the incidence of MAC bacteremia was 5.6% in the clarithromycin group and 15.5% in the placebo group. Clarithromycin also conferred an improved survival rate. More than half of the patients in the clarithromycin group who developed bacteremia were infected with clarithromycin-resistant isolates.[28]

Rifabutin 300 mg/d is an alternative to macrolides for MAC prophylaxis. However, rifabutin-associated drug interactions and complications (eg, uveitis) complicate the use of this agent. Patients should be monitored closely for side effects.

If the patient's CD4 count rises to more than 100 cells/µL for a sustained period after the initiation of antiretroviral therapy and the HIV viral load response is good, prophylaxis can possibly be discontinued.

Previous
Next

MAC Lymphadenitis

MAC lymphadenitis in children is treated with surgical excision of the affected lymph nodes, resulting in a cure rate that exceeds 90%. Antibiotics are generally not required but may be beneficial in patients with extensive lymphadenitis or with a poor response to surgical therapy. However, MAC lymphadenitis in immunocompromised patients, including patients with HIV infection/AIDS, generally responds to 6-12 months of antimycobacterial therapy and does not require surgery.[19]

A randomized Dutch study found no significant difference in healing time with antibiotic therapy versus a conservative wait-and-see approach in children with advanced nontuberculous mycobacterial cervicofacial lymphadenitis. The study included 50 children (age range, 14–114 mo) whose lymphadenitis was predominantly due to M avium or M hemophilum. The median time of resolution in the group receiving rifabutin and clarithromycin was 36 weeks, compared with 40 weeks for the wait-and-see group.[29]

Previous
Next

Hot-Tub Lung

The role of antimycobacterials and corticosteroids in the treatment of hypersensitivity pneumonitis-like lung disease (hot-tub lung) due to MAC infection remains controversial. Removing environmental sources and avoiding exposure to infected aerosols are the best preventive measures.[4] Patients with severe lung disease or respiratory failure should be treated with prednisone tapered over 4-8 weeks. Immunocompromised patients and those with bronchiectasis also benefit from a short course (3-6 months) of anti-MAC treatment.[18]

Previous
Next

Consultations and Long-Term Monitoring

Consultants for MAC infections in patients with AIDS include an infectious diseases specialist, a general surgeon for lymph node biopsy, a gastroenterologist for liver biopsy, and a hematologist-oncologist for bone marrow biopsy.

Consultants for patients with lung disease who develop pulmonary MAC infection include an infectious diseases specialist, a pulmonologist occasionally if surgical resection or biopsy of lungs is desired, and a cardiothoracic surgeon. Consultants for lymphadenitis in children include an infectious diseases specialist, a general surgeon, and an ear, nose, and throat (ENT) specialist.

Carefully monitor patients with AIDS for adverse effects of medications, especially for hepatotoxicity and uveitis. They may also require blood transfusions if anemia is significant. Patients should also be monitored for immune reconstitution inflammatory syndrome (IRIS). Antiretroviral (ARV) drugs should be continued in patients who have been taking them. But for those patients who are not taking ARVs, they should be started 2 weeks after initiating antimycobacterials to avoid IRIS.[25]

Carefully monitor patients with lung disease who develop pulmonary MAC infection for improvement in symptoms and for adverse effects of medications.

After completion of treatment, patients should be monitored clinically and, if needed, radiologically for relapse of the infection. Patients in whom MAC infection is suspected based on a single culture result or radiographic findings but who do not meet diagnostic criteria for MAC disease, and consequently do not undergo treatment, require close follow-up for clinical and radiographic monitoring.

Previous
 
 
Contributor Information and Disclosures
Author

Janak Koirala, MD, MPH, FACP, FIDSA Professor and Division Chair, Division of Infectious Diseases, Department of Internal Medicine, Southern Illinois University School of Medicine

Janak Koirala, MD, MPH, FACP, FIDSA is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, International AIDS Society, International Society for Infectious Diseases, International Society of Travel Medicine, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Aaron Glatt, MD Chief Administrative Officer, Executive Vice President, Mercy Medical Center, Catholic Health Services of Long Island

Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American Association for Physician Leadership, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Klaus-Dieter Lessnau, MD, FCCP Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author William B Harley, MD,to the development and writing of the source article.

References
  1. Nishiuchi Y, Maekura R, Kitada S, et al. The recovery of Mycobacterium avium-intracellulare complex (MAC) from the residential bathrooms of patients with pulmonary MAC. Clin Infect Dis. 2007 Aug 1. 45(3):347-51. [Medline].

  2. Dhillon SS, Watanakunakorn C. Lady Windermere syndrome: middle lobe bronchiectasis and Mycobacterium avium complex infection due to voluntary cough suppression. Clin Infect Dis. 2000 Mar. 30(3):572-5. [Medline].

  3. Hartman TE, Jensen E, Tazelaar HD, et al. CT findings of granulomatous pneumonitis secondary to Mycobacterium avium-intracellulare inhalation: "hot tub lung". AJR Am J Roentgenol. 2007 Apr. 188(4):1050-3. [Medline].

  4. Sood A, Sreedhar R, Kulkarni P, Nawoor AR. Hypersensitivity pneumonitis-like granulomatous lung disease with nontuberculous mycobacteria from exposure to hot water aerosols. Environ Health Perspect. 2007 Feb. 115(2):262-6. [Medline].

  5. Feller M, Huwiler K, Stephan R, et al. Mycobacterium avium subspecies paratuberculosis and Crohn's disease: a systematic review and meta-analysis. Lancet Infect Dis. 2007 Sep. 7(9):607-13. [Medline].

  6. Koirala J, Adamski A, Koch L, Stueber D, El-Azizi M, Khardori NM, et al. Interferon-gamma receptors in HIV-1 infection. AIDS Res Hum Retroviruses. 2008 Aug. 24(8):1097-102. [Medline].

  7. Koh WJ, Jeong BH, Jeon K, Lee NY, Lee KS, Woo SY, et al. Clinical Significance of the Differentiation between Mycobacterium avium and Mycobacterium intracellulare in M. avium Complex Lung Disease. Chest. 2012 May 24. [Medline].

  8. Thomson RM, Armstrong JG, Looke DF. Gastroesophageal reflux disease, acid suppression, and Mycobacterium avium complex pulmonary disease. Chest. 2007 Apr. 131(4):1166-72. [Medline].

  9. Mycobacterium avium Complex. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/dbmd/diseaseinfo/mycobacteriumavium_t.htm. Accessed: August 15, 2011.

  10. Cassidy PM, Hedberg K, Saulson A, McNelly E, Winthrop KL. Nontuberculous mycobacterial disease prevalence and risk factors: a changing epidemiology. Clin Infect Dis. 2009 Dec 15. 49(12):e124-9. [Medline].

  11. Maugein J, Dailloux M, Carbonnelle B, et al. Sentinel-site surveillance of Mycobacterium avium complex pulmonary disease. Eur Respir J. 2005 Dec. 26(6):1092-6. [Medline].

  12. Freeman J, Morris A, Blackmore T, et al. Incidence of nontuberculous mycobacterial disease in New Zealand, 2004. N Z Med J. 2007 Jun 15. 120(1256):U2580. [Medline].

  13. Han XY, Tarrand JJ, Infante R, et al. Clinical significance and epidemiologic analyses of Mycobacterium avium and Mycobacterium intracellulare among patients without AIDS. J Clin Microbiol. 2005 Sep. 43(9):4407-12. [Medline].

  14. Gordin FM, Sullam PM, Shafran SD, et al. A randomized, placebo-controlled study of rifabutin added to a regimen of clarithromycin and ethambutol for treatment of disseminated infection with Mycobacterium avium complex. Clin Infect Dis. 1999 May. 28(5):1080-5. [Medline].

  15. Hayashi M, Takayanagi N, Kanauchi T, Miyahara Y, Yanagisawa T, Sugita Y. Prognostic Factors of 634 HIV-Negative Patients with Mycobacterium avium Complex Lung Disease. Am J Respir Crit Care Med. 2012 Mar 1. 185(5):575-83. [Medline].

  16. Perrin C. A patient with acquired immunodeficiency syndrome (AIDS) and a cutaneous Mycobacterium avium intracellulare infection mimicking histoid leprosy. Am J Dermatopathol. 2007 Aug. 29(4):422. [Medline].

  17. Kitada S, Kobayashi K, Ichiyama S, et al. Serodiagnosis of Mycobacterium avium-complex pulmonary disease using an enzyme immunoassay kit. Am J Respir Crit Care Med. 2008 Apr 1. 177(7):793-7. [Medline].

  18. [Guideline] 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. 2007 Feb 15. 175(4):367-416. [Medline]. [Full Text].

  19. Kasperbauer SH, Daley CL. Diagnosis and treatment of infections due to Mycobacterium avium complex. Semin Respir Crit Care Med. 2008 Oct. 29(5):569-76. [Medline].

  20. Davis KK, Kao PN, Jacobs SS, et al. Aerosolized amikacin for treatment of pulmonary Mycobacterium avium infections: an observational case series. BMC Pulm Med. 2007 Feb 23. 7:2. [Medline].

  21. Selby W, Pavli P, Crotty B, et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease. Gastroenterology. 2007 Jun. 132(7):2313-9. [Medline].

  22. Lam PK, Griffith DE, Aksamit TR, Ruoss SJ, Garay SM, Daley CL. Factors related to response to intermittent treatment of Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2006 Jun 1. 173(11):1283-9. [Medline].

  23. Field SK, Cowie RL. Treatment of Mycobacterium avium-intracellulare complex lung disease with a macrolide, ethambutol, and clofazimine. Chest. 2003 Oct. 124(4):1482-6. [Medline].

  24. Jenkins PA, Campbell IA, Banks J, Gelder CM, Prescott RJ, Smith AP. Clarithromycin vs ciprofloxacin as adjuncts to rifampicin and ethambutol in treating opportunist mycobacterial lung diseases and an assessment of Mycobacterium vaccae immunotherapy. Thorax. 2008 Jul. 63(7):627-34. [Medline].

  25. [Guideline] Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009 Apr. 58:1-207. [Medline].

  26. Chaisson RE, Keiser P, Pierce M, Fessel WJ, Ruskin J, Lahart C, et al. Clarithromycin and ethambutol with or without clofazimine for the treatment of bacteremic Mycobacterium avium complex disease in patients with HIV infection. AIDS. 1997 Mar. 11(3):311-7. [Medline].

  27. de Silva TI, Cope A, Goepel J, et al. The use of adjuvant granulocyte-macrophage colony-stimulating factor in HIV-related disseminated atypical mycobacterial infection. J Infect. 2007 Apr. 54(4):e207-10. [Medline].

  28. Pierce M, Crampton S, Henry D, et al. A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome. N Engl J Med. 1996 Aug 8. 335(6):384-91. [Medline].

  29. Lindeboom J. Conservative wait-and-see therapy versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children. Clin Infect Dis. Jan 15 2011. 52(2):180-4.

  30. Ichikawa K, van Ingen J, Koh WJ, Wagner D, Salfinger M, Inagaki T, et al. Genetic diversity of clinical Mycobacterium avium subsp. hominissuis and Mycobacterium intracellulare isolates causing pulmonary diseases recovered from different geographical regions. Infect Genet Evol. 2015 Oct 2. [Medline].

 
Previous
Next
 
CT thorax of a 77-year-old woman who presented with chronic cough and sputum production, without a history of underlying pre-existing lung disease. Sputum culture grew Mycobacterium avium complex. The diagnosis was Lady Windermere syndrome.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.