Transcript Diagnosis, Treatment, and Prevention of Nontuberculous

Diagnosis, Treatment, and Prevention of
Nontuberculous Mycobacterial Diseases
American Thoracic Society Documents
Am J Respir Crit Care Med 2007; 175:367416
www.atsjournals.org
Diagnostic Criteria
CXR, or chest HRCT on non-cavitary disease
3 or > sputum for AFB
Exclusion of other pulmonary dis, eg TB
Mycobacterium avium complex (MAC), M kansasii,
M abscessus
Pulmonary symptoms, nodular or cavity in CXR, HRCT
shows multifocal bronchiectasis with nodules
Positive culture: 2 sputums or 1 bronchial lavage
Lung biopsy with granuloma or AFB, culture+NTM
Susceptibility testing for
MAC: clarithromycin only
M kansasii: rifampin only
M fortuitum, M abscessus, M chelonae:
amikacin, imipenem, doxycycline, the
fluoroquinolones, a sulfonamide, cefoxitin,
clarithromycin, linezolid, tobramycin
Prophylaxis and Treatment of NTM Disease
MAC Pulmonary Disease
Nodular/bronchiectatic MAC lung disease;initial
3 times weekly regimen
Clarithromycin 1000 mg or azithromycin 500 mg
Rifampin 600 mg
Ethambutol 25 mg/Kg
Follow with sputum culture monthly
Treatment to be continued until culture negative for
1 year
Prophylaxis and Treatment of NTM Disease
MAC Pulmonary Disease
Fibrocavitary or severe nodular/bronchiectasis,init
Daily treatment
Clarithromycin 500-1000 or azithro 250/day
Rifampin 600 mg,or rifabutin 150-300 mg
Ethambutol 15 mg/Kg,
+/- 3 times weekly amikacin or streptomycin for 3
months.
Treatment continued until culture negative for 1
year.
Treatment of Macrolide-resistant MAC Lung
Disease
Analogous to treatment for drug resistant TB
Risk factor for resis: macrolide monotheray,
inadequate companion drug use.
Parenteral aminoglycoside: parenteral
streptomycin or amikacin
Surgical resection (debulking)
4 drug regimen: INH, Rifampin, ethambutol,
streptomycin for 3-6 mo moxifloxacin?
INF gamma?
MAC disseminated
Clarithromycin 500 mg bid or azithro 500/d
Ethambutol 15 mg/K/d
+/- Rifabutin 300 mg/d (interferes with metabolism
of protease inhibitors and mononucleoside
reverse transcriptase inh.
Therapy discontinued with resolution of symptoms
and reconstitution of cell mediated immune
function (CD4 count >100/mcL for 12 mo).
Otherwise, treatment should be life long.
Prophylaxis of Disseminated MAC disease
When CD4 T-lymphocyte count is
<50cells/mcL
Azithromycin 1200 mg/week or
clarithromycin 1000 mg/d or rifabutin 300
mg/d
Treatment of M kansasii pulmonary disease
INH 300 mg/d
Rifampin 600 mg/d
Ethambutol 15 mg/d
Until culture negative for 1 year.
Treatment for M abscessus pulmonary
disease
No drug regimen.
Clarithromycin 1000 mg/d and multidrug reg
Surgical resection of localized disease
Treatment of nonpulmonary disease by
RGM (M abscessus, M chelonae, M
fortuitum)
Based on in vitro susceptibilities.
M absessus: a macrolide regimen is often
used.
Treatment of NTM cervical adenitis
Mostly due to MAC
Surgical resection with >90% cure rate
A macrolide-based regimen for extensive
MAC lymphadenitis.
Epidemiology on NTM
Widely distributed in the environment.
Organisms found in soil and water, both
natural and treated water sources.
M kansasii, M xenopi, M simiae almost
exclusively from municipal water sources.
No evidence of animal-to-human or humanto-human transmission of NTM.
Human disease acquired from environ
exposures.
Epidemiology
NTM diseases in most industrialized
countries: 1.0-1.8 cases per 100,000.
CDC report of NTM: 75% pulmonary, 5%
blood, 2% skin and soft tis, 0.4% lymph n.
1 mil population: MAC 29-36 isol, M
fortuitum 4.6 to 6 isol, M kansasii 2-3.1 isol
Southeastern US: higher isolation rates
Pathogenesis
HIV: disseminated NTM infection typically occurred only
after CD4 T-lymphocyte is <50/microliter.
In non-HIV, disseminated NTM infection assoc with specific
mutation in INF gamma and IL-12 synthesis and
response path. IFN-gamma receptor 1, IFN-gamma
receptor 2, IL-12 receptor beta1 subunit, IL-12 subunit
p40. the signal transducer and activator of transcription
1, and the nuclear factor-kappa beta essential modulator.
An association between bronchiectasis, nodular pulmonary
NTM infection and particular body habitus in
postmenopausal woman: pectus excavatum, scoliosis,
mitral valve prolapse.
Host Defense
Mycobacteria phagocytosed by
macrophages, which produce IL-12, which
up-regulates IFN-gamma. INF-gamma
activates neutrophils and macrophages to
kills intracellular pathogens.
Positive feed back loop between INFgamma and IL-12. Disseminated NTM is
manifestation of immunologic defect.
Pulmonary Disease with NTM
Predisposing lung diseases
COPD
Bronchiectasis (NTM often coexist)
CF
Pneumoconiosis
Prior TB
Pulmonary alveolar proteinosis
Esophageal motility disorders
Body Morphotype
Woman with nodular NTM pulmonary
infections associated with bronchiectasis
have similar clinical characteristics and
body type. So called Lady Windermere’s
Scoliosis, pectus excavatum, mitral valve
prolapse and joint hypermobility
Hypersensitivity-like Lung Disease
MAC exposure associated with hot tub use
(“hot tub lung”)
MAC has predisposition for growth in indoor
hot tubs.
Mycobacteria are relatively resistant to
disinfectants and wide range of temp.
Metal working fluids may cause similar disM. immunogenus, a rapidly growing M.
Hot Tub Lung
Subacute onset of dyspnea, cough, fever
Occas hypoxemic respiratory failure
Non-smokers
Chest HRCT: diffuse nodular all over
Culture from sputum, bronchial washing,
tissue biopsy isolating MAC
Treatment: removal, antimicrobials,
corticosteroids.
Tumor Necrosis Factor Inhibition
NTF-alpha blocking agents, blocking
antibodies infliximab and adalimumab and
the soluble receptor etanercept lead to
relatively high rate of active TB in latent
infection.
Relevance to NTM unknown