Mycobacterium and Lung Disease

1. MycobacteriumandLung Disease • Tze-Ming Benson Chen, M.D., F.C.C.P. • San Francisco Critical Care Medical Grp • California Pacific Medical Center

2. Disclosures • none

3. Case Presentation • 84 year old woman presents with chronic cough. No hemoptysis, fevers, chills, night sweats, and or weight loss. Has noticed progressive fatigue. • No tobacco abuse history • Born and raised in China, immigrated to U.S. in 2010

4. Chest CT • tree-in-bud opacities • respiratory bronchioles & alveoli obstruction • differential diagnoses: • Mycobacterial • fungal • Viral • Non-infectious inflammatory Diseases

5. Mycobacterium

6. Differential Diagnosis • Mycobacterium Tuberculosis • Atypical mycobacterium • Rapid Growers • Chelonei, Fortuitum, Abscessus • Slow growers • Avium Complex

7. Tuberculosis • Three forms of pulmonary tuberculosis • Latent tuberculosis • Active pulmonary parenchymal tuberculosis • Pleural disease • Tuberculosis Empyema • Tuberculous Pleuritis

8. Latent Tuberculosis • Tuberculosis present but not causing an active infection • Diagnosis • PPD • Quantiferon Gold • High risk individuals should be tested • HIV • immigrants from endemic countries • homeless • health care professionals • persons living or working in long-term care facilities

9. PPD Interpretation * Prior BCG vaccination is not considered when determining PPD reaction size

10. BCG Effectiveness *Alaskan natives and American Indians vaccinated between 1935 and 1938 as part of a clinical trial *52% (95% CI: 27%, 69%) reduction in TB incidence JAMA 2004;291:2086-91

11. Quantiferon Gold • First approved by the FDA in 2005 as aid in diagnosing both latent and active TB • Enzyme-linked immunosorbant assay to detect the release of interferon-gamma • Requires fresh heparinized whole bood • incubated with 2 antigens found on TB but not in BCG vaccine • False positives with mycobacterium Kansasii, marinum, and szulgai • reproducibility decreased if result is close to cut-off value

12. QFT-G Studies • 216 Japanese nursing students at low risk for TB • Spec 98.1% • 118 patients with culture confirmed TB • Sens 89.0% • Compare QFT-G to TST • 99 Korean healthy BCG-vaccinated medical students • Spec QFT-G: 96% vs. TST: 49% • 54 patients with pulmonary TB • Sens QFT-G: 81% vs. TST: 78% AJRCCM 2004;170:59-64 JAMA 2005;293:2756-61

13. QFT-G Studies • In 318 unselected hospitalized patients • sens for TB disease • QFT-G: 67% vs TST: 33% • Indeterminate results in patients with negative TST • QFT-G: 21% AJRCCM 2005;172:631-5

14. Reactivation Risk • Reactivation of tuberculosis • Risk dependent upon patient’s underlying health and time since initial TB infection AJRCCM 2000;161:S221-47

15. Latent TB Treatment • Determine that patient does not have active TB • History and physical exam • Chest x-ray http://www.cdc.gov/tb/publications/factsheets/treatment/LTBItreatmentoptions.pdf

16. INH Hepatotoxicity • Risk Factors • Regular alcohol use • Hepatotoxic Tx • CYP P450 inducers • Liver disease • Pregnancy / immediate postpartum • IVDA • Female Am Rev Respir Dis 1978;117:991

17. INH Treatment • Administer recommended regimen • Provide pyridoxine if on INH • Evaluate patient monthly in clinic and repeat blood work if suspicious of hepatotoxicity • Discontinue therapy if: • AST > 5x upper nml if Asx • AST > 3x upper nml if Sx • Obtain baseline Tbil, AST, ALT, Alk Phos • baseline liver disease • HIV • pregnant and postpartum (< 3months) • Alcohol use • medications with potential interactions • otherwise at your discretion

18. Pulmonary TB • Classic Symptoms • Cough, Fatigue, Weight loss, Sweats, Hemoptysis • Classic Radiographic FIndings • Upper lobe opacities • Tree-in-bud opacities to cavitary consolidation

19. Pleural TB • TB Pleuritis • Immunologic reaction to pulmonary TB infection • Often culture negative • Often self-limited • High risk for active pulmonary TB • TB Empyema • Presence of TB organism in pleural space causing active infection • AFB smear • Culture positive

20. TB Treatment • Initial: 4 drug therapy for 2 months • Continuation: 2 drug therapy for additional 4 months if TB is sensitive to INH and Rifampin • Today, Directly Observed Therapy via Dept of Public Health is standard of care

21. TB Tx: Pleural Disease • TB Pleuritis • If suspected, pursuit of diagnosis is essential because of high risk of developing active pulmonary disease within the next 12 months • TB Empyema • Chest tube drainage • Will likely require VATS • initiate 4-drug therapy and contact Dept of Public Health

22. Atypical Mycobacterium • Symptoms: • chronic cough • fatigue • Occasionally: • hemoptysis • dyspnea • weight loss • Radiographic findings: • Tree-in-bud to consolidation • bronchiectasis

23. Lady Windermere • Thin caucasian woman with chronic cough • Bronchiectasis involving middle lobe and lingula • Chronic atypical mycobacterial infection • Possible link to cystic fibrosis

24. Diagnosis • Symptoms • Radiographic findings • Microbiology • 2 of 3 expectorated sputums positive for same organism • 1 bronchoscopic specimen that is culture positive for atypical mycobacterium

25. Treatment • Decision to treat • Not straightforward • Consider: • Severity of symptoms • Severity of radiographic abnormalities • Patient preference • “Rapid” grower vs “slow” grower

26. MAC Treatment • Clarithromycin / azithromycin • Rifampin / rifabutin • Ethambutol • Treatment is usually between 12 and 18 months • 12 months of treatment following initial negative respiratory culture

27. Back to the Case • Sputum culture positive for MAC • Decision made to not treat with antibiotics • Recommended either acapella valve therapy or theravest for airway clearance • Reimage in 6 to 12 months

28. Questions?