Three cases of infection with pulmonary Mycobacterium Avium complex with resistance to macrolides secondary to prolonged prior use for bronchectasis
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Pulmonologist, Lecturer, Aristotle University of Thessaloniki
Pulmonologist, Director, Department of Tuberculosis, Athens Chest Hospital “Sotiria”
Pulmonologist, Tuberculosis Department, Athens Chest Hospital “Sotiria”
Pulmonologist, Head, Tuberculosis Department, Athens Chest Hospital “Sotiria”
Corresponding author
Apostolos Papavasileiou   

Department of Tuberculosis, Athens Chest Hospital “Sotiria” 152 Mesogeion Ave, Athens 11527, Greece
Pneumon 2013;26(2):190-195
The activity of atypical or non tuberculous mycobacteria (NTM) as pulmonary pathogens has been recognized even in immunocompetent individuals. The Mycobaterium avium complex (MAC) is the commonest of the 130 NTMs and comprises two species, M. avium and M. intracellulare. For the treatment of pulmonary MAC infection combination of a macrolide (azithromycin or clarithromycin) with rifampicin and ethambutol is required. An aminoglucoside (streptomycin or amikacin) should be added in cavitational or severe disease. The treatment is long and expensive, of uncertain efficacy and with serious adverse effects. One quarter of patients either fail to become culture negative or relapse despite treatment. In addition, only 52% of appropriately treated patients show clinical improvement. Resistance to macrolides is a significant negative prognostic factor. As in the case of antituberculosis drugs, the main mechanism of resistance development is prior exposure to monotherapy. Three cases are presented of MAC pulmonary infection with resistance to macrolides, which probably developed secondary to prolonged use for the treatment of exacerbations or maintenance therapy of bronchiectasis. Because of the increasing prevalence of NTM infection, the presence of nodules and bronchiectasis in a patient with pulmonary symptoms should raise the suspicion of NTM disease. The administration of macrolides without sufficient evidence poses the danger of development of resistance in the case of undiagnosed NTM disease, and testing for acid-fast bacilli is imperative before initiation of treatment of bronchiectasis with macrolides.
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;175: 367–416.
Winthrop KL, McNelley E, Kendall B et al. Pulmonary nontuberculous mycobacterial disease prevalence and clinical features: an emerging public health disease. Am J Respir Crit Care Med 2010 Oct 1;182(7):977-82.
Gitti Z, Mantadakis E, Maraki S, Samonis G. Clinical significance and antibiotic susceptibilities of nontuberculous mycobacteria from patients in Crete, Greece. Future Microbiol 2011 Sep;6(9):1099-109.
Griffith DE. Therapy of nontuberculous mycobacterial disease. Curr Opin Infect Dis 2007;20(2):198-203.
Griffith DE, Aksamit TR. Therapy of refractory nontuberculous mycobacterial lung disease. Curr Opin Infect Dis 2012;25(2):218 27.
Amsden GW. Anti-inflammatory effects of macrolides--an underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother 2005;55(1):10-21.
Manika K, Kioumis I. The clinical significance of Streptococcus pneumoniae resistance in community-acquired pneumonia. Pneumon 2011, 24(4):379-387.
Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases. Chest 2010;138(5):1202-12.
Kudoh, S. Erythromycin treatment in diffuse panbronchiolitis. Curr Opin Pulm Med 1998;4(2):116-21.
Bell SC, Senini SL, McCormack JG. Macrolides in cystic fibrosis. Chron Respir Dis 2005;2(2):85-98.
King P. Is there a role for inhaled corticosteroids and macrolide therapy in bronchiectasis? Drugs 2007;67(7):965-74.
Flume PA, O’Sullivan BP, Robinson KA et al. Cystic Fibrosis Pulmonary Guidelines. Chronic Medications for Maintenance of Lung Health. Am J Respir Crit Care Med 2007;176:957–969.
Anwar GA, Bourke SC, Afolabi G, Middleton P, Ward C, Rutherford RM. Effects of long-term low-dose azithromycin in patients with non-CF bronchiectasis. Respir Med 2008;102(10):1494-6.
Wong C, Jayaram L, Karalus N, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet 2012;380(9842):660-7.
Serisier DJ, Martin ML. Long-term, low-dose erythromycin in bronchiectasis subjects with frequent infective exacerbations. Respir Med 201;105(6):946-9.
Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax 2010;65 Suppl 1:i1-58.
Altenburg J, de Graaff CS, van der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics - part 2: advantages and disadvantages of long-term, low-dose macrolide therapy. Respiration 2011;81(1):75-87.
Mandell LA, Wunderink RG, Anzueto A; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl. 2):S27–72.
Consensus Workshop of the Hellenic Society of Infectious Diseases, the Hellenic Society of Chemotherapy and the Hellenic Thoracic Society. Guidelines for the diagnosis and empiric treatment of community acquired pneumonia. In: Guidelines for the Diagnosis and Empiric Treatment of Infections, from: Hellenic Center for Diseases Control and Prevention, Scientific Committee of Nosocomial Infections. Editor: Hellenic Society of Infectious Diseases. Athens 2007, pp 33-46.
Kuroishi S, Nakamura Y, Hayakawa H, Shirai M, Nakano Y, Yasuda K, Suda T, Nakamura H, Chida K. Mycobacterium avium complex disease: prognostic implication of high-resolution computed tomography findings. Eur Respir J 2008;32(1):147-52..
Maiga M, Siddiqui S, Diallo S, et al. Failure to recognize nontuberculous mycobacteria leads to misdiagnosis of chronic pulmonary tuberculosis. PLoS One 2012;7(5):e36902.
Zheng C, Fanta CH. Non-tuberculous mycobacterial pulmonary infection in the immunocompetent host. QJM. 2013 Jan 29. [Epub ahead of print].
Kobashi Y, Yoshida K, Miyashita N, Niki Y, Oka M. Relationship between clinical efficacy of treatment of pulmonary Mycobacterium avium complex disease and drug-sensitivity testing of Mycobacterium avium complex isolates. J Infect Chemother 2006;12(4):195-202.
Kitada S, Uenami T, Yoshimura K, et al. Long-term radiographic outcome of nodular bronchiectatic Mycobacterium avium complex pulmonary disease. Int J Tuberc Lung Dis 2012;16(5):660-4.
van Ingen J, Boeree MJ, van Soolingen D, Mouton JW. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria. Drug Resist Updat 2012;15(3):149-61.
Kim EY, Chi SY, Oh IJ, et al. Treatment outcome of combination therapy including clarithromycin for Mycobacterium avium complex pulmonary disease. Korean J Intern Med 2011;26(1):54-9.
The Research Committee of the British Thoracic Society. Pulmonary disease caused by Mycobacterium avium-intracellulare in HIV-negative patients: five-year follow-up of patients receiving standardised treatment. Int J Tuberc Lung Dis 2002; 6(7):628–634.
Ito Y, Hirai T, Maekawa K, et al. Predictors of 5-year mortality in pulmonary Mycobacterium avium-intracellulare complex disease. Int J Tuberc Lung Dis 2012;16(3):408-14. doi: 10.5588/ ijtld.11.0148. Epub 2012 Jan 5.
Griffith DE, Brown-Elliott BA, Langsjoen B, et al. Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. Am J Respir Crit Care Med 2006;174(8):928-34. Epub 2006 Jul 20.
Craft JC, Notario GF, Grosset JH, Heifets LB. Clarithromycin resistance and susceptibility patterns of Mycobacterium avium strains isolated during prophylaxis for disseminated infection in patients with AIDS. Clin Infect Dis 1998;27(4):807-12.
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