Mycobacteriumand

Lung DiseaseTze-Ming Benson Chen, M.D., F.C.C.P.

San Francisco Critical Care Medical GrpCalifornia Pacific Medical Center

Disclosures

none

Case Presentation84 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

Chest CTtree-in-bud opacities

respiratory bronchioles & alveoli obstruction

differential diagnoses:

Mycobacterial

fungal

Viral

Non-infectious inflammatory Diseases

Mycobacterium

Differential DiagnosisMycobacterium Tuberculosis

Atypical mycobacterium

Rapid Growers

Chelonei, Fortuitum, Abscessus

Slow growers

Avium Complex

TuberculosisThree forms of pulmonary tuberculosis

Latent tuberculosis

Active pulmonary parenchymal tuberculosis

Pleural disease

Tuberculosis Empyema

Tuberculous Pleuritis

Latent TuberculosisTuberculosis 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

PPD InterpretationSize of Induration (mm) Population

At least 5mmRecent TB contact Immunosuppresed- HIV, organ Txp, TNF antagPrior Infx on imaging

At least 10mm

Recent ImmigrantsIVDAHigh risk employmentDiseases that increase riskChildren exposed to high risk individualsChildren < 4

At least 15mm Anyone* Prior BCG vaccination is not considered when determining PPD reaction size

BCG Effectiveness60 year f/u Total Number TB Incidence

per 100,000

BCG Vaccine 1483 66

Placebo 1309 138

*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

Quantiferon GoldFirst 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

QFT-G Studies216 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

QFT-G StudiesIn 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

Reactivation Risk

Reactivation of tuberculosis

Risk dependent upon patient’s underlying health and time since initial TB infection

AJRCCM 2000;161:S221-47

Latent TB TreatmentDetermine that patient does not have active TB

History and physical exam

Chest x-ray

http://www.cdc.gov/tb/publications/factsheets/treatment/LTBItreatmentoptions.pdf

INH HepatotoxicityRisk Factors

Regular alcohol use

Hepatotoxic Tx

CYP P450 inducers

Liver disease

Pregnancy / immediate postpartum

IVDA

Female

Age Risk

20-34 0.3%

35-49 1.2%

50-64 2.3%

> 65 4.6%

Am Rev Respir Dis 1978;117:991

INH TreatmentAdminister 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

Pulmonary TBClassic Symptoms

Cough, Fatigue, Weight loss, Sweats, Hemoptysis

Classic Radiographic FIndings

Upper lobe opacities

Tree-in-bud opacities to cavitary consolidation

Pleural TBTB 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

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

TB Tx: Pleural DiseaseTB 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

Atypical MycobacteriumSymptoms:

chronic cough

fatigue

Occasionally:

hemoptysis

dyspnea

weight loss

Radiographic findings:

Tree-in-bud to consolidation

bronchiectasis

Lady WindermereThin caucasian woman with chronic cough

Bronchiectasis involving middle lobe and lingula

Chronic atypical mycobacterial infection

Possible link to cystic fibrosis

DiagnosisSymptoms

Radiographic findings

Microbiology

2 of 3 expectorated sputums positive for same organism

1 bronchoscopic specimen that is culture positive for atypical mycobacterium

TreatmentDecision to treat

Not straightforward

Consider:

Severity of symptoms

Severity of radiographic abnormalities

Patient preference

“Rapid” grower vs “slow” grower

MAC TreatmentClarithromycin / azithromycin

Rifampin / rifabutin

Ethambutol

Treatment is usually between 12 and 18 months

12 months of treatment following initial negative respiratory culture

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

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