Tuberculosis

     

    2007 CTS (6th Ed)
    "infectious Diseases: A clinical short course" 2nd ed. Frederick Southwick. 2008
    Canadian TB standards 2013

     

    Etiology

    • Mycobacterium, encased in coat that resists destaining with acid.
    • Humans ONLY reservoir.
    • Transmission: person aerosolizes the TB bactera in droplet nuclei become inhaled into alveoli
    • Once Infected:
      • If normal immune system clears - no infection
      • If inhaled in large numbers - immune system encases into a granula --> latelt TB
    • Latent TB has 10% lifetime chance of converting to active TB (50% of that is in the first 2 years)
    • 94% of toronto cases are foreign born, 2% are MDR (multi drug resistant)
    • 2 billion people worldwide have latent TB, 9 million/year develop active disease.
      • Many co-infected with HIV

     

    Microbiology

    • Mycobacterium tuberculosis aerobic non-motile bacillus with waxy lipid-rich outer wall with high concentration of mycolic acid.Outer lipid was resists Gram stain.
      • Need to heat to melt outer wall, and stain with red dye fuchsin, and resists acid-alcohol decolorization.
      • Resists killing by macrophages and PMNs.
    • Rate of growth is slow, 1/20th of most bacteria.  (waxy cell wall inhibits nutrient access).
    • Survive and grow in macrophages.TBimage.jpg
      • Increasing numbers of macrophages are activated to sercrete cytokines:
        • Interleukin 1: hypothalamus --> fever.
        • Tumor Necrosis Factor: lipid metabolism, severe weight loss.  Fever, night sweats, weight loss.
    • When enter lungs, eaten by macrophages, transported to hilar lymph nodes.
      • In lymph nodes, macrophages present tubercular proteins to T-cells.
      • T-cells activate macrophages to kill TB.
      • Accumulation of cell wall waxes --> formation of granulomas
        • Granulomas --> clusters of epithelioid cells, giant cells, and lymphocytes.
          • Over time centers of granulomas become necrotic, forming cheesy debris called "caseous necrosis.
            • Caseating granulomas are hallmark lesion of TB!!!!

    Transmission & Risk Factors

    • Humans ONLY reservoir.
    • Transmission: person aerosolizes the TB bactera in droplet nuclei become inhaled into alveoli
      • Infectivity depends on # of organisms per microscopic field
      • High infectivity:
        • Laryngeal TB
        • HIV (high load)
        • Large cavitary lesions
      • Repeated exposure and close contact is required.
      • High burden in world b/c crowded living conditions.
      • (Mid 1980's highest TB due to AIDS epidemic.  In 2002 lowest level recorded 5.2 cases/10000, but now rising due to immigration).

    Assessment of a TB Clinic Patient

    • Review the Canadian TB Standards
    • If positive TB skin test:
      • First one?  Repeat test? (evidence of recent conversion to positive?)
      • BCG Vaccine? and When? (Neonatal BCG vaccine = low likelihood of positive TST, >2yo BCG = high likelihood!)
      • Follow up chest Xray? (typically done after positive TST)
    • Any symptoms of Active TB? (Cough (chronic), hemoptysis, fevers, chills, night sweats, weight loss, appatite changes)
    • Social Hx: Country of origin, date of immigration.
    • Risk Factors for Exposure:
      • Direct Exposure
        • Exposure to Friend/Relative with TB **** MOST COMMON
        • Healthcare Worker
        • Living in or traveling to endemic countries (Top 5: Mexico, Phillipines, India, Vietnam, China), (Asians/Hispanics)
      • Crowded Environment
        • Homelessness
        • Shelters, Refugee Camps
        • Prison Inmates
      • Poor Cell-Mediated Immunity (lower chance of initial clearance)
        • People infected with HIV
        • Extremes of Age (less cell-mediated immunity)
        • Comorbidities: Diabetes, ESRD, Malnutrition
        • Cancers, Chemotherapy, Autoimmune treatments
      • Genetic predisposition  **New**
        • Black, Hispanic, Asia Pacific islanders, and Native Americans (5-10x incidence of caucasians).
        • (Caucasians/Europeans are more resistant likely b/c devastating TB in industrial revolution - 1/4 deaths in Europe)
    • Risk Factors for Activation:
      • Risk Estimated Risk

        Estimated

        Relative Risk

        HIGH Acquired Immunodeficiency Syndrome 110-170
        HIV 50-110
        Transplant (immune-suppressant) 20-74
        Silicosis 30
        ESRD Requiring Dialysis 7-50
        Carcinoma of Head and Neck 11.6
        Recent TB infection (≤2 years) 15.0
        Abnormal Chest Xray (Fibronodular Disease) 6-19
        MODERATE TNF-alpha Inhibitors 1.5-5.8
        Diabetes Mellitus (all types) 2-3.6
        Steroid Treatment (≥15mg/d prednisone) 4.9
        Young age of infection (0-4 years) 2.2-5

        SLIGHTLY

        INCREASED

        High Alcohol Consumption (≥3 drinks/day) 3-4
        Underweight (<90% ideal BW, ≤20 BMI) 2-3
        Cigarette Smoker (1 pack/day) 1.8-3.5
        Abnormal Chest Xray (Granuloma) 2
        LOW

        Person with positive TST, no known RF's

        normal Chest Xray

        1 (Reference)
        VERY LOW

        Positive Two-Step TST (booster),

        No other known risk factor and normal CXR

        0.5

     

    Types of Infection

    Primary Tuberculosis

    • Patient inhales infectious M. tuberculosis droplets for the first time.
      • A flu-like illness usually follows (or no symptoms).
      • Activated macrophages control spread.
        • Lesions heal spontaneously and form fibrosis/calcification called "Ghon lesions".
        • Ghon lesion + hilar adenopathy is called "Ranke complex".
        • Macrophages transport TB to hilar lymph nodes, where T-cells help them destroy TB.
        • However, some remain in the lymph nodes, and gain access to the thoracic duct, enter bloodstream, and spread through the body.
      • TB LOVES areas of low oxygen tension (lots of oxygen) and low lymphatic flow:
        • Kidneys
        • Long-bone epiphyses
        • Vertebral bodies
        • Apices of lungs
      • Most TB removed initially, but some remain for decades kept in check by immune system.
        • When immune system depressed --> TB flourishes!!!

     

    Miliary Tuberculosis

    • In some patients initial exposure fails to induce a cell-mediated response (or not strong enough!)
      • Can occur as primary or reactivation of latent.
    • Mycobacteria multiply, disseminate, causing "Miliary TB".
    • Risk factors:
      • Age
        • Very young
        • Very old
      • Immunosuppressed:
        • On immunosup. drugs.
        • HIV
        • Pregnant
      • Other
        • Alcoholism
        • Renal Failure
        • Connective tissue diseases.
    • Physical Exam of Miliary TB:
      • Nothing specific: fever, anorexia, weakness, weight loss, night sweats.
      • Chronically ill, 5% may have choroid tubercles on fundoscopy (need pupil dilated)
      • Diagnosis is missed in 50%
      • 20% identified post-mordem.
    • Investigations:
      • WBC usually normal unless "leukemoid reaction"  extremely high >30k >40k
      • Maybe LFTs elevated.
      • Hyponatremia (from adrenal insufficiency or siADH) --> well known!
      • Can measure AM or PM cortisol to exclude adrenal insufficiency.
      • Chest Xray:
        • 1/3 may have small nodules (0.05 to 1mm) resembling millet seeds "Miliary".
    • TBmiliarytb.jpg         TBmillet.jpg
      • Negative Chest xray does not exclude diagnosis!!!
      • In some patients, ARDS may develop- complete opacification of lungs.
      • Sputum samples positive rarely!
      • Samples for histopathology (biposies) (Look for granulomas, acid-fast bacilli, cultures)
        • Enlarged lymph nodes
        • Liver biopsy
        • Bone Marrow
      • Transbronchial biopsy high yield!
      • Blood cultures (often positive in AIDS)
      • CSF if CNS symptoms.
    • The key to diagnosis of miliary TB: high index of suspicion.
    • Need to treat ASAP:
      • 4 drug combination:
        • INH
        • Rifampin
        • Pyrazinamide
        • Ethambutol

     

    Secondary Tuberculosis (Reactivation)

    • Reactivation of latent TB occurs in 10% of patients, and half of that risk is within first 2 years)
      • Often this reactivation is in eldelry, men 30-50yo
    • Symtomps of reactivation:
      • Often asymptomatic
        • Evidence of reactivation found only on CXR
        • If the infection is not detected, symptoms worsen over several months.
      • Later: worsening cough w/ sputum, low-grade fever, night sweats, fatigue, and weight loss.
        • Symptoms of advanced disease:
          • Hemoptysis (erosion of TB cavity into arteriole)
          • Pleuritic chest pain (tuberculous pleural effusion or pleural involvement)
      • May be able to hear apical rales on exam.
      • Hallmark of reactivated TB is apical cavitary lesions on CXR.  (post. segments of upper lobes).
        • Can get lordotic views for help
        • CT is better to assess extent of disease.
        • May not cavitate in HIV... may even have normal CXR.
      • Individuals with cavitary lesions are highly infectious!!!
        • NEED respiratory isolation, while AFB smears and cultures are obtained.

    Latent TB

    • Not infectinos
    • Diagnosed on TST or IGRA

    Symptoms

    Symptoms of Active TB

    • Prolonged cough (>3w) and sputum (almost always insidious)
    • Prolongued low-grade fever.
      • Interleukin release from TB-filled macrophages.
    • chills, night sweats, weight loss, fatigue, loss of appetite
      • These are "B-symptoms" from Tumor Necrosis Factor (TNF) release of TB-filled macrophages.
    • Signs of SEVERE disease:
      • Hemoptysis  (cavitary lesions eroded into arteriole)
      • Pleuritic chest pain (Pleural involvement or tuberuclous pleural effusion)
    • Other (i.e. Lymphadenopathy)

     

    • Extrapulmonary or Disseminated Disease (often in immunocompromised, HIV)
      • Lymph Nodes, Bones, Jones, Pleura
      • GU, peritoneal, maningeal, cardial, tracheal. 

     

    Symptoms of Latent TB

    • NONE!

    Diagnosis

    • TB Skin Test
      • See section below
    • Interferon Gamma Release Assay ($90-100, rarely covered)
      • Measure release of interferon-gamma in blood by T-cells in response to TB antigens.
        • As sensitive as TST but more specific.
        • Same as TST, bigger response needed for low-risk person.
        • Not recommended for testing individuals for low risk of latent TB or development of active TB.  Exception is testing those with increased risk in future.
      • Indications for IGRA
        • Received BCG vaccine or as cancer therapy
        • People unlikely to return for interpretation
        • NOTE: TB skin test is preferred for children younger than 5 years.  (lower IGRA sensitivity).
      • If positive, then need to ask symptoms (fever, chills, nt sweats, wt loss, cough)
        • Need to do CXR, sputum to R/O active disease.
        • If active disease ruled out, then make diagnosis of "latent TB".
    • Sputum sample (AM is higher yield).  Send for Acid Fast Smear + Culture.
    • Classic test:
      • (Indicated for highly suspected Active TB)
        • Ziehl-Nielson acid-fast sputum smear x 3.    (60% sensitivity of each)
          • morning sputum is higher yield
          • 3 smears! to exclude diagnosis.  (cavitary release is intermittent)
          • Even if positive, does not confirm diagnosis, need culture for confirmation.
        • Culture is most sensitive and specific test!
          • Automated fluorometric culture system take 9-16 days, detect microbial metabolism.
          • Conventional growth in Lowenstein-Jensen medium is 3-4 and up to 6 weeks.  (1/20th cell growth rate)
        • NAAT (PCR) is 95% sensitive and very specific (often done to confirm AFB).
          • Technically challenging, need specialized lab.
          • PPV is >95% in pts with AFB positive smears.
          • Positive in 50-80% in AFB-negative culture positive smears.
          • Treat if positive regardless if sputum AFB smear is positive of negative.
          • Do not use if suspicion is low because PPV is 50% in this setting.
    • Bronchoscopy
      • BAL and biopsy can be considered for suspected TB with negative sputum studies.
      • Pleural TB --> biopsy to detect granulomas (pleural pleural cultures 25% yield).
        • Pleural biopsy yields is better than pleural fluid culture (granulomas in 75% of pts)
        • Some experts recommend measuring pleural adenosine deaminase level to establish pleural TB foe excudative lymphocytic effusions. 
    • CSF:
      • Suspected tuberculous meningitis
      • CSF releals lymphocytic pleocytosis, decreased glucose, elevated protein.
      • CSF AFB stains are usually negative (25%)
      • CSF cultures usually negative too (25%)
      • PCR for TB: 98% specificty, but ~50% sensitivity to diagnose TB meningitis.

    Imaging

    • Primary Progressive
      • Localized infiltrate or paratracheal/hilar lymphadenopathy
    • Reactivation:
      • Fibrocatitary lesions in superior segments of lower lobes or apical posterior segments of upper lobes.
    • Atypical patterns: (more likely in AIDs)
      • Miliary
      • Middle or lower lung zones.
      • Mediastinal lymphadenopathy
      • Pleural involvement.
    • CT: Subtle pulmonary TB

     

    What to do with positive TST or IGRA

    1. Exclude Active Disease
      • Look for signs/symptoms of active disease:  (See "Symptoms Of Active TB Section")
        • Pulmonary: Cough
        • B-sx: Fever, chills, night sweats, weight loss.
        • Chest Xray
        • Sputum Sample or another sample.
    2. Exclude False Positives
    3. If active disease is ruled out, diagnosis of latent TB is made.
      • Decide if requires treatment
      • Decision is often difficult, must balance risk of treatment (hepatotoxicity etc..) vs. risk of developing active TB
        • See "Clinic Assessment" for risk factors for developing active TB.

    Treatment

    Drugs

    • Prior to starting treatment check:
      • Hep B/C serology, Plts, AST/ALT/ALP, bili, creatinine.
      • Color vision/ acuity if ethambutol to be used. 
    • DOT
      • Directly observed therapy if cannot guarantee pt will take drug, ongoing transmission can occur.
    • Drug Side Effects Notes

      Isoniazid (INH)

       

      - Peripheral neuropathy

        (if high risk of neuropathy give Vitamin B6 [pyridoxine]

        includes: diabetics, uremia, EtOH, HIV, malnutrition,

        seizure disorder, pregnancy)

      - Rash, Liver enzyme elevation; hepatitis; lupus-like

        syndrome

      - Hepatitis risk increases 

        with age and EtOH consumption

      - Adjust for AKI

      - Pyridoxine can prevent

      peripheral neuropathy

      Rifampin

       

      - Hepatitis; rash; GI upset;

      - Colors body fluids orange

      - Caution with protease inhibitors and 

        non-nucleoside rev-transcriptase inh.

      - Avoid in pts taking squinavir/ritonavir

      Pyrazinamide

      - Hepatitis; rash; GI upset; hyperuricemia

      - Difficult glucose control in DM patients

      - Adjust for renal injury

      Ethambutol

       

      - Optic neuritis; rash

      - Baseline + monitor visual acuity and color

        vision. (call immediately if changed)

      - Adjust for AKI.

      Rifabutin

      - Rash; hepatitis; thrombocytopenia; severe arthralgia;

        uveitis; leukopenia

      - Adjust dose with protease inhibitors and

        NNRT inhibitors.

      - Monitor retroviral activity and rifabutin toxicity

      Rifapentine

      (NEW!)

      - Similar to rifampin

      - Contraindicated in HIV-pos patients 

       (high risk of failure/relapse)

      Second Line .... not discussed here.  
    • NOTE:
      • Rifamycins (Rifampin, Rifabutin, Rifapentine) potent inducers of cytochrome P450 --> INR drops on warfarin.
    • WHO Criteria to render patient non-infectious:
      • 1.  Adequate treatment for tuberculosis for at least 2 weeks
      • 2.  Improvement of symptoms
      • 3.  Three consecutive negative sputum smears (collected at 8- to 24-hour intervals, including one early morning collection).

     

    Active TB

    • Either via primary progressive disease or reactivation of LTBI.
    • Treatment difficult because:
      • Mycobacteria grow slowly
      • Difficult to kill latent organisms within cavitary lesions.
      • Because TB load is often high, high incidence of resistance.
    • Need Two or more agents to reduce risk or resistance.
      • INH --> 1 in 10^6 resistant.
    • Typically 4 drug regimens.  (specialized area)
        • Phase 1: 2mo of Isoniazid, Rifampin, Ethambutol, Pyrazinamide
          • 2 week interruption = restart treatment all over
        • Phase 2: (Continuation phase): Isoniazid + Rifampin x 4-7mo (7mo if cavitary lesions or positive sputum repeat culture)
          • 9-12mo of therapy for meningitis, but idea duration unknown.
    • Recommended:
      • 4-drug regimen of first-line agents X 2 months. (INH, rifampin, pyrazinamide, and ethambutol or streptomycin)
        Followed by:
      • INH, Rifampin, and pyrazinamide X4 months.
    • If MDR-TB suspected, consult ID, need sensitivities.
      • Can still use aminoglycosides and Fluoroquinolones.
    • DOT therapy:
      • Directly Observed Therapy (DOT) --> observed treatment.  For:
        • Unreliable patients.
        • Those with INH or Rifampin resistance
    • Adjunctive steroids for:
      • Tuberuclous meningitis
      • Tuberuclous pericarditis

    Latent TB / Prevention

    • Hallmark of latent TB diagnosis is the TB Skin Test (TST)
    • See TST Section
    • Need treatment
        • Three options:
        • 1. Isoniazid x 9mo + Vitamin B6 (if neuropathy risk)
        • 2. Rifampin x 3mo
        • 3. Rifampentene + Isoniazid x3mo of DOT once weekly.

         
    • NOTE: patients with HIV or other serious immunocompromise who are close contacts of person with active TB must be treated as LTBI irrespective of TST or IGRA result once active TB is excluded.

    Resistance

    • High resistance because organism load is high
      • 1 in 10^6 organisms resistant to INH and 10^9-10^10 organisms in cavitary lesion
        • With two agents: 10^6 X 10^6 = 10^12 (chance of resistant to both), which is more than in a cavitary lesion.
      • Worldwide INH resistance 7.3%.  (8% in US)
    • Resistance is classified into
      • Primary  resistance - > Patient never received anti-TB therapy.
      • Secondary resistance --> Previous cultures from this pt were negative.
        • High risk: Homeless, IV drug users, AIDS.
    • Multi-Drug Resistant TB (MDR-TB)   (2% of TB in US)
      • Resistant to at least Isoniazid (INH) and Rifampin
      • Need to treat with 3 or more agents.
        • (HUGE problem in 1990's, but better infection control and 4-drug therapies helped).
      • Highest places are Eastern Europe (14%)
      • Need extensive resistance testing to direct therapy, longer treatment duration, and many agents.
    • Extensively drug resistant TB (XDR-TB)
      • Resistant to fluoroquinolones and one aminoglycoside (i.e. one of:):
        • Kanamycin, Capreomycin, Amikacin.
      • Recently reported in South Africa.
      • Mortality 90%

    Prevention/ BCG

    • BCG derived from an attenuated strain of mycobacterium bovis.
    • Widely used worldwide and not administered in US/Canada
    • BCG vaccine is most effective for preventing disseminated disease and TB meningitis in children, protective effects in adults is variable.
    • It is a live vaccine, can cause disseminated disease in immunocompromised (do not give to immunocompromised pts).

    Tuberculin Skin Test (TST)

    • Standard of care for diagnosing Latent TB (LTBI) in Canada is TST
    • Indication of a delayed-type hypersensitivity reaction
    • How to administer:
      • TST: 5 tuberculin units (0.1 ml) of purified protein derivative-standard (PPD-S) given intradermally on the volar aspect of the arm.
      • Once injected, raises a weal of 5 mm diameter which disappears in 10 – 15 minutes.
        • Injecting deeper is ineffective... blood stream clears protein.
      • Read at 48 to 72 hours by a trained health professional.  Measure only the transverse diameter of induration, not erythema. Record in mm.
    • Conversion occurs within 8wks of exposure.
    • NOTE: repetitive skin tests in whose who are positive will continue to increase the size of reaction (booster effect)
    • NOTE: TBST: 20-30% false negative in active TB

    Interpretation

    • (Can use algorithm below or use calculator: http://www.tstin3d.com/)
    • Typically take into account induration size and the cutoff for positive skin test.
      • Rationalle is that some people may not be able to mount a good response (i.e. HIV or active TB).

     

    1. TST Size

    • CANADIAN GUIDELINES (Taken from the Canadian TB standards, 7th edition)

    TSTInterpretationCanada.png

    • US Guidelines (MKSAP 16) 2014
    • ≥ 5mm ≥ 10mm ≥ 15mm

      - HIV-positive

      - Recent contact with active TB

      - Fibrotic changes in CXR consistent

        w/ old TB

      - Organ transplants or other immunosuppressive

        conditions (≥15mg/d prednisone for >4weeks)

      - Recent <5y arrivals from high

        prevalence countries

      - Injection drug users

      - High congregate areas (Prisons,

        jails, nursing homes, long-term

        facilities for elderly, hospitals

        health care facilities, residential

        facilities for AIDs pts, homless shelters

      - Mycobacteriology lab personnel;

        clinical conditions w/ high risk for active

        disease

      - Children <4yo or exposed to adults

        in high-risk categories

      - Everyone else with no

        risk factors.

    • NOTE: For repeat testing, positive TST considered if increase in induration ≥10mm in 2 years.

    2. Predictive value of TST (BCG or NTM)

    • False negatives:
      • Active TB (20%)
      • Age <6mo
      • Recent infection <8w
      • Overwhelming TB
      • Recent vaccination with live virus (measles)
      • Recent viral infection.
      • Anergy
    • False positive
      • BCG vaccine
        • Previous BCG (basically matters only if >1yo)
          • BCG received <1yo: 1% had TST result >10mm tested >10y later
          • BCG received 1-5yo: 10-15% positive TST up to 25y later
          • BCG received: >6yo: 40% persistent positive reactions
      • Non-tuberculous mycobacteria
        • found in soil+water in warm temperate climates, people exposed can be sensitized
        • Sensitization uncommon in Canada (Quebec study showed 5% of all reactions >10mm was due to cross-reactivity

    3. Risk of active TB

    • AIDS (110-170x times risk)
    • HIV (50-110x)
    • Transplant (20-74x)
    • Silicosis (30x)
    • CKD with Dialysis (10-25x)
    • Carcinoma of head and neck (16x)
    • Recent TB infection <=2 (15x)

     

    Management of Positive TST

    • Positive Test implies that sometime in past has been exposed to TB.
    • Rule out Active TB
      • Hx + Px
      • CXR
      • Sputum if symptoms or abnormal CXR --> need AM sputum X3  (+/- refer to TB clinic)
      • TB.png

     

    2 Step TST

    • For those that will undergo serial testing (to establish baseline).
      • Useful if remote exposure to TB antigens (BCG, prev infection, atypical mycobacterium), as immune response to them may have waned.
      • The initial test "boosts" the immune response (if previously exposed), improves reliability of the 2nd test.
      • The 2nd test tests for response.
    • 2 Step Skin Test
      • A single TBST may be negative, but stimulate an anamnestic immune response (Stronger second-exposure rxn)
      • A second TBST is done 1-4weeks later.
      • If a person has been infected in past, the second TBST will be >10mm (positive)

     

    Non-Tuberucous Mycobacteria

    • Environmental bacteria found in soil and natural/treated water.
    • Most identified species are non-pathogenic, but some can cause pulmonary infections.
    • Often colonizers of medical equipment and surgical solutions.
      • Causes nosocomial transmission.
    • Tend to affect young adults and elderly persons.
    • Risk Factors (triad)
      • Structural Lung Disease: COPD, Bronchiectasis, CF, Pneumoconiosis, Esophageal motility disorders
      • Body Morphotype: Slender body habitus, pectus excavatum, scoliosis, mitral valve prolapse.
      • Immune Status: Interferon gamma, Interleukin 12 pathways.
    • Syndromes:
      • PulmonaryM. avium complex, M. kansasii, M. abscessus, M. xenopi, M. malmoense
      • LymphadenitisM. avium complex, M. malmoense, M. scrofulaceum
      • Skin/SoftTissue/MSK: M. abscessus, M. chelonae, M. fortuitum, M. marinum, M. ulcerans
      • Disseminated (i.e. HIV) M. avium complex, M. kansasii, M. abscessus, M. xenopi, M. genavense, M. haemophilum, M. chelonae 
        • Mostly advanced HIV disease, maybe TNF-alpha blockers (unknown)
      • (Health-Care Associated: M. abscessus, M. chelonae, M. fortuitum)
    • Diagnosis:
      • Same techniques as TB: cultures!
      • Detected from sites generally thought to be sterile --> infection.
        • Often unknown if colonization or infection.  Diagnostic criteria developed to see which pts require tx.
      • Criteria:  (See guidelines for details)
        • Imaging criteria: cavitary nodular lung lesions on XR/CT
        • Pulmonary symptoms
        • Laboratory criteria (positive isolation of NTM) from at least two separate sputum specimens (often contaminant, consult ID) or one BAL sample or histopathology for AFB, or granulomatous disease with positive lung culture.

    M. avium 

    is most common

    • Inhaled aerosolized of organisms from colonized soil and water.
    • Types of presentations:
      • 1. Fibrocavitary Disease - similar to TB
        • Often upper lobes, middle aged men with hx of smoking or chronic lung injury and middle-aged/elderly women with no hx of smoking or lung disease.
        • Cavitary lung lesions with thin cavity walls (M. tuberculosis is thick wall cavities).
      • 2. Lady Widermere Syndrome
        • Middle aged or elderly women with no hx of smoking or underlying lung disease.
        • Chronic cough, nodular infiltrates, nodular bronchiectatic disease invole frequently RML or Lingula.
        • Indolent course, some pts may have aggressive disease with fever/wt loss resp insufficiency.
      • 3. "Hot Tub Lung"  (Hypersensitivity pneumonitis).
        • Linked to inhalation of household water colonized by MAC.
        • Subacute --> dyspnea, cough, fever.
        • Resolve when removing aerosol.
      • 4.  Lymphadenitis (head and neck)
        • MAC (80%) of pts, usually in children. 
      • 5.  Disseminated MAC
        • Mostly in HIV pts, esp with CD < 50/uL.
    • Treatment:
      • Antimicrobial therapy.. (susceptibility testing not indicated)
        • Macrolide (clarithromycin, azithromycin) + ethambutol + rifamycin (rifampin or rifabutin)
          • Amikacin or streptomycin for first 2-3mo of therapy with severe/ poorly controlled MAC
        • For Hypersensitivity pneumonitis: Can use steroids (hastens recovery).
        • For Lymphadenitis: Excisional surgery alone.
      • Complex management, poor response to treatment.. May need to resect lobe.
      • Consult ID

    Mycobacterium kansasii 

    • Second most common causing lung disease.
    • Present with signs/sx suggestive of TB.
    • Not found in natural invironments, only in urban/municipal water supplies.
    • Single isolate is NEVER colonization, should always be considered diagnostic of disease.
    • Treatment:
      • Isoniazid, rifampin, ethambutol x 18mo
      • Results of sputum cultures must be negative x12mo before therapy discontinued.

     

    Rapidly Growing Mycobacteria

    • Brief growing period if culture (7 days)
    • Widely distributed in nature. 
    • Three most relevant: 
      • M. fortuitum
      • M. abscessus
      • M. chelonae
    • Many clinical manifestations: pulmonary, soft tissue, MSK.
    • Often direct inoculation with cosmetic procedures, exposure to colonized liquid (mostly tap water).
    • Dissemination is rare, unless immunocompromised.
    • Susceptibility varies, must get in vitro susceptibilities, and tx with multiple drugs.
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