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Complex Disease

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  • Author: Charles L. Daley1
  • Editor: David Schlossberg2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO 80206; 2: Philadelphia Health Department, Philadelphia, PA
  • Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
  • Received 31 January 2017 Accepted 13 February 2017 Published 21 April 2017
  • Charles L. Daley, daleyc@njhealth.org
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  • Abstract:

    Despite the ubiqitous nature of complex (MAC) organisms in the environment, relatively few of those who are infected develop disease. Thus, some degree of susceptibility due to either underlying lung disease or immunosuppression is required. The frequency of pulmonary MAC disease is increasing in many areas, and the exact reasons are unknown. Isolation of MAC from a respiratory specimen does not necessarily mean that treatment is required, as the decision to treatment requires the synthesis of clinical, radiographic, and microbiologic information as well as a weighing of the risks and benefits for the individual patient. Successful treatment requires a multipronged approach that includes antibiotics, aggressive pulmonary hygiene, and sometimes resection of the diseased lung. A combination of azithromycin, rifampin, and ethambutol administered three times weekly is recommend for nodular bronchiectatic disease, whereas the same regimen may be used for cavitary disease but administered daily and often with inclusion of a parenteral aminoglycoside. Disseminated MAC (DMAC) is almost exclusively seen in patients with late-stage AIDS and can be treated with a macrolide in combination with ethambutol, with or without rifabutin: the most important intervention in this setting is to gain HIV control with the use of potent antiretroviral therapy. Treatment outcomes for many patients with MAC disease remain suboptimal, so new drugs and treatment regimens are greatly needed. Given the high rate of reinfection after cure, one of the greatest needs is a better understanding of where infection occurs and how this can be prevented.

  • Citation: Daley C. 2017. Complex Disease. Microbiol Spectrum 5(2):TNMI7-0045-2017. doi:10.1128/microbiolspec.TNMI7-0045-2017.

Key Concept Ranking

Infection and Immunity
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Major Histocompatibility Complex Class I
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/content/journal/microbiolspec/10.1128/microbiolspec.TNMI7-0045-2017
2017-04-21
2017-11-23

Abstract:

Despite the ubiqitous nature of complex (MAC) organisms in the environment, relatively few of those who are infected develop disease. Thus, some degree of susceptibility due to either underlying lung disease or immunosuppression is required. The frequency of pulmonary MAC disease is increasing in many areas, and the exact reasons are unknown. Isolation of MAC from a respiratory specimen does not necessarily mean that treatment is required, as the decision to treatment requires the synthesis of clinical, radiographic, and microbiologic information as well as a weighing of the risks and benefits for the individual patient. Successful treatment requires a multipronged approach that includes antibiotics, aggressive pulmonary hygiene, and sometimes resection of the diseased lung. A combination of azithromycin, rifampin, and ethambutol administered three times weekly is recommend for nodular bronchiectatic disease, whereas the same regimen may be used for cavitary disease but administered daily and often with inclusion of a parenteral aminoglycoside. Disseminated MAC (DMAC) is almost exclusively seen in patients with late-stage AIDS and can be treated with a macrolide in combination with ethambutol, with or without rifabutin: the most important intervention in this setting is to gain HIV control with the use of potent antiretroviral therapy. Treatment outcomes for many patients with MAC disease remain suboptimal, so new drugs and treatment regimens are greatly needed. Given the high rate of reinfection after cure, one of the greatest needs is a better understanding of where infection occurs and how this can be prevented.

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Figures

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FIGURE 1

Prevalence of pulmonary NTM cases among a sample of U.S. Medicare part B enrollees aged 65 and older, 1997 to 2007. From reference 29 , with permission.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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FIGURE 2

Interplay between environmental exposure, host susceptibility, and pathogen virulence.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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FIGURE 3

Chest CT scan with coronal (A) and transverse (B) images from a patient with fibrocavitary pulmonary MAC. Bilateral upper lobe cavitation is noted, with associated volume loss in the setting of severe emphysema.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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FIGURE 4

Chest CT scan from a patient with nodular bronchiectatic MAC, demonstrating multiple pulmonary nodules throughout both lungs, including tree-in-bud nodularity in the dependent sections below the right middle lobe and lingula.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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FIGURE 5

Treatment algorithm for MAC disease. If the isolate is macrolide susceptible and no cavities are present on chest imaging, a three-times-a-week 3-drug regimen is recommended. If cavitary changes are present, daily administration is recommended along with addition of parenteral amikacin (or streptomycin) and consideration of lung resection for focal disease. For macrolide-resistant disease, parenteral amikacin and lung resection should be strongly considered. IV, intravenous.

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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Tables

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TABLE 1

Organisms belonging to MAC

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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TABLE 2

Risk factors for NTM infection and disease

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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TABLE 3

Spectrum of pulmonary diseases caused by MAC

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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TABLE 4

2007 ATS diagnostic criteria for NTM lung disease

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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TABLE 5

Antimicrobial agents useful for treatment of MAC infection

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017
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TABLE 6

Recommendations for medical treatment of MAC disease ( 102 )

Source: microbiolspec April 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.TNMI7-0045-2017

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