1. Mycobacterium and Lung 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 Size of Induration (mm)Population At least 5mm R ecent TB contact Immunosuppresed - HIV, organ Txp, TNF antag Prior Infx on imaging At least 10mm Recent Immigrants IVDA High risk employment Diseases that increase risk Children exposed to high risk individuals Children < 4 At least 15mmAnyone * Prior BCG vaccination is not considered when determining PPD reaction size

10. BCG Effectiveness 60 year f/uTotal Number TB Incidence per 100,000 BCG Vaccine148366 Placebo1309138 *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/LTBItreatmentopt ions.pdf

16. INH Hepatotoxicity Risk Factors Regular alcohol use Hepatotoxic Tx CYP P450 inducers Liver disease Pregnancy / immediate postpartum IVDA Female AgeRisk 20-340.3% 35-491.2% 50-642.3% > 654.6% 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. 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 Back to the Case

28. Questions?