Transcript Chronic Pulmonary Disease

University of Wisconsin School of Medicine and Public Health
“55 year old female with acute
respiratory illness”
Barb Stowe-Carpenter, M.D.
Professor of Medicine
Department of Medicine / General Internal Medicine
Primary Care Conference Presentation
Wednesday, June 14, 2006
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Disclaimer
•
I have not received research support from
pharmaceutical companies.
•
I am not a consultant or paid speaker for any
pharmaceutical companies.
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Learning Objective
•
Review Nontuberculous mycobacterial diseases
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March 2006
55 yo female presents in March 2006 with acute
respiratory illness
Patient was in Bahamas had 5d T>101, pleuritic chest
pain, productive cough with some blood, marked
dyspnea
In ER found to be hypoxic O2 Sat 85%, WBC 16,000
Chest x-ray showed mixed interstitial and parenchymal
disease In right lung and left lung base
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Past Medical History
2002
• s/p partial colectomy for ruptured appendix or diverticula and
left ovariectomy
• Abnormal CT of lung noted at preop
• Over the course of the next two years, fluctuating pulmonary
nodules and interstitial lung disease, emphysema changes
with apical bleb
• Only symptom was DOE on two flights
 (-) PPD
 (-) sputum x3
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Past Medical History
2002
• 25 py smoking history, no smoking in 10 years
• FEV1 2.59 FVC 3.85 FEF 25-75% 38%
• DLCO 57%
• pH 742, pCO2 36, pO2 62
• Bronchoscopy and washing for AFB and culture MAC
• Treatment was begun Azithromycin, rifabutin, ethambutol
• Stayed on three months and discontinued because of losing
job
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NG
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02/23/2006
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02/24/2006
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04/25/2006
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RS
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03/27/2006
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05/11/2006
10/07/2003
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MAI
Table 1
©2006 UpToDate®
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Epidemiology
•
Sources
 Most NTM organisms have been isolated
from water and soil
 Animal to human transmission is not an
issue
 Human to human transmission is rare
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Prevalence
 MAC 1.1/100,000
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Clinical Presentation
and Diagnostic Criteria
1. Chronic Pulmonary Disease
2. Lymphadenitis
3. Skin and soft tissue infection
4. Disseminated Disease
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Chronic Pulmonary Disease
•
Generally older
– Common Symptoms:



Chronic cough
Sputum production
Fatigue
– Other Symptoms:






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Malaise
Dyspnea
Fever
Hemoptysis
Weight loss
Chest pain
NTM often occurs in the context of pre-existing lung
disease especially COPD, bronchiectasis,
pneumonoconiosis, cystic fibrosis, previous TB
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Chronic Pulmonary Disease (cont’d)
•
MAC—3 major clinical presentations
1. Disease in middle age or elderly male
•
•
+/- Etohic and/or smoker with underlying lung
disease
Looks like TB with upper lobe infiltrates and cavities,
cough, weight loss
2. Disease in Areas of Bronchiectasis
3. Disease associated with nodular reticular pattern or
interstitial lung disease in nonsmoking women >50
*Solitary nodules and dense consolidation have been
described
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Chronic Pulmonary Disease (cont’d)
•
Colonization is quite rare
•
Contamination and transient infection does occur
•
HRCT has been instrumental in defining disease and
showing that there is slow progression
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Table 2
©2006 UpToDate®
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Lymphadenitis
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Usually in children 1-5 years old
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80% is MAC
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Unilateral 95%
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Rare systemic symptoms
•
Nodes enlarge rapidly
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Sinus tracts and fistulas develop with prolonged
drainage
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Skin and Soft Tissue Infection
•
Usually M. fortuitum, M absessus, M. marinum, M.
ulcerans
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“swimming pool granulara” fish tank granuloma
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Bursa joints tendon sheaths and bones can also be
infected. These can be nosocomial or from
contamination in the environment
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Disseminated Disease
•
Immunosuppressed—cardiac transplant, chronic
steroids, leukemia
•
AIDS rare unless CD4<50
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90% have prolonged fevers
•
Symptoms: night sweats, weight loss, abdominal pain,
diarrhea, decreased WBC, anemia, increase Alk phos
HSM, retroperitoneal lymphadenopathy, cough and other
pulmonary symptoms
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Treatment: Pulmonary Disease
MAC Usually multi drug
1. Clarithromycin 500 mg bid or Azithromycin 250 mg q day
or 500 mg tiw
2. Ethambutol 25 mg/Kg/d x 2 mo then 15 mg/Kg/d
3. Rifampin or rifabutin
+/- intermittent streptomycin 2-3 mo for extensive
disease
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Treatment: Pulmonary Disease (cont’d)
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Treatment recommended 12 mo post negative sputum
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Cheek sputums q month
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Should show clinical improvement 3-6 mo
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Cultures should be negative within 12 mo
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Surgery in MAC if poor response to therapy or macrolide
resistance in patient with disease in 1 lobe
•
Susceptibility testing recommended to macrolide if
previously treated on a macrolide
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M. kansasii
•
Since rifampin success rate has improved (nearly
100%), surgery has no role in routine cases
•
Usual regimen: INH 300 mg/day, rifampin 600 mg/day,
ethambutol 25 mg/Kg/day x 2 mo, then 15 mg/Kg/day x
18 mo (at least 12 mo of negative cultures)
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Treatment: Lymphadenitis
•
Usually caused by MAC or M. scrofulaceum
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Treat by excision 95% successful without chemotherapy
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Treatment: Skin Tissue Skeletal Disease
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Usually a combination of excisional surgery and
chemotherapy (drug therapy 6-12 mo)
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Treatment: Disseminated MAC
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In AIDS—median survival 134 days, 13% alive at 1 year
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Multi-drug with clarithromycin or azithromycin,
ethambutol, rifabutin ( preferred because can still use
indinavir), rifampin (cannot be used with protease
inhibitors)
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Prophylaxis of Disseminated
Disease in AIDS
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Has been shown to be effective
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Development of resistance is a concern
•
Clarithromycin decreased incidence of disseminated
disease from 16% to 6%
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Rifabutin decreased incidence from 17% to 8%
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Azithromycin was shown to be effective at 1200 mg/wk
+/- rifabutin
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Treatment in Rapidly Growing Mycobacterial
Disease
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Isolates of M. fortuitum are susceptible to Amikacin 100%,
Cipro 100%, Sulfonamides 100%, Cefoxitin 80%, imipenem
100%, Clarithromycin 80%, doxycycline 50%
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Isolates of M. abscessus are susceptible to Clarithromycin
100%, Clofazimine, amikacin 90%, Cefoxitin 70%,
imipenem 50%
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Isolates of M. chelonae are susceptible to Amikacin 80%,
tobramycin 100%, clarithromycin 100%, imipenem 60%,
clofazimine , doxycycline 25%, Cipro 25%
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Usually causes cutaneous disease
•
Some minor infections resolved spontaneously or after
surgical debridement
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Treatment in Rapidly Growing Mycobacterial
Disease (cont’d)
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Pulmonary disease is increasingly being recognized
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>60 year old female nonsmoker with underlying disease
like lung damage from previous TB, GI disorders
especially chronic vomiting, cystic fibrosis,
bronchiectasis
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Tends to be indolent
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Drug Toxicity
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GI Intolerance: clarithromycin, azithromycin, rifabutin,
rifampin
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Abnormal LFTs: clarithromycin azithromycin, rifabutin,
rifampin, INH, ethionamide
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Decreased WBC: rifabutin
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Impaired visual acuity and color vision: ethambutol
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Auditory and Vestibular Function: streptomycin, amikacin,
clarithromycin, azithromycin
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Renal Function: Streptomycin, Amakacin
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Peripheral Neuropathy: Ethanbutol
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Clarithromycin enhances rifabutin toxicity especially uveitis
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Bibliography
1. UpToDate including ATS Guidelines: Diagnosis and
Treatment of Disease caused by non-TB mycobacteria.
2006
2. Diagnosis and Treatment of Disease caused by
Nontuberculosis mycobacteria, Am Rev Respir Dis
1990;142(4):940-53.
3. Reich, J and Johnson RE. Mycobacterium avium
complex pulmonary disease. Am Rev Respir Dis
1991;143(6):1381-5.
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