Mycobacteriosis

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Mycobacteriosis

• Clinical correlations

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Mycobacteria

• Tuberculosis
• Leprosy (Hansen Disease)
• BCG hypersensitivity and infection
• MOTT
• AIDS related disseminated MAC
• Immune reconstitution disease

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Mycobacteria

• All species resist decoloration, i.e. acid fast
• All cause granulomatous inflammation
• All are more common and/or more severe with cell
  mediated immune dysfunction
• Delayed diagnosis if not specifically sought
• Only TB spread person to person

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When to suspect Mycobacterial disease

• Cavitary, reticulonodular or tree-in-bud pattern
  on CXR
• Underlying structural lung disease
• Cellular immune dysfunction
• Subacute or chronic fever, sweats or weight loss,
  esp. along with CBC abnormality
• Any unexplained respiratory symptom/sign in
  patient with HIV
• Cosmetic, plastics esp. breast, or bioprosthetic
  valve surgery
• Granulomatous inflammation

May coexist with other active or inactive lung
process
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Dx of Mycobacteria

• Smear- acid fast stains (Kinyoun, auramine)
  rare false positives
• Culture all species other than M.tb and M.
  leprae must be correlated clinically
• PCR currently only for interpretation
  respiratory secretion smear () and PCR ()
  means TB, smear () but PCR (-) means MOTT, smear
  (-) but PCR () means TB
• Histology granulomatous inflammation narrows
  differential greatly even if stains (-) for AFB

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Mycobacterium leprae

• Unique infection able to manifest full spectrum
  from nearly absent to intense granulomatous
  immune response
• Temperate climates worldwide
• La., Ark., Tx., Miss. in USA
• Not grown in vitro
• Respiratory tract entry, seeks cooler areas
• Infects schwann cells causing neuropathy

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Histology of Leprosy
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Acid-Fast Stain M. leprae
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MOTT

• Over 100 species, most of little, no or unknown
  virulence
• Similar to TB in histology and staining, trained
  technicians can distinguish
• All can be normal flora except M.kansasii
• None person to person
• Diagnosis requires more than simply recovering
  from non-sterile specimen

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MOTT Classification

• Growth-rate /morphologic system obsolete
• Clinically useful to classify by host, organ
  system (pulmonary vs. lymphatic, cutaneous,
  disseminated)
• Treatment varies greatly with species

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MOTT Risk Factors

• Structural lung disease (MAC, kansasii,)
• Trauma/surgical (M.marinum, rapid growers)
• Cellular immune defect (rapid growers, MAC)
• Gamma interferon/IL-12 defect
• AIDS (MAC, rapid growers, genevensa, hemophilum)
• Recurrent aspiration, achalasia (MAC, rapid
  growers)
• Fish tank (M.marinum)
• Reptiles ( M chelonei)
• Children Scrofula (M. scrofula, MAC)
• Hot-Tubs Hypersensitivity pneumonitis (MAC)

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TABLE 4 Characteristics of patients with
nontuberculous mycobacteria pulmonary
infections
MAC M.xenopi
M. kansasii RGM/non-CF
Subjects n
125 66
34 16 Underlying
conditions Pre-existing pulmonary disease
89 (71.2) 28 (42.4) 7 (20.6)
8 (50) Previous M. tuberculosis
35 (28) 17 (25.8)
9 (26.5) 3 (18.7)
Immunosupression/transplantation 34 (27.7)
17 (25.8) 5 (14.7) 1 (6.2)
None/anorexia
14 (11.2) 18 (27.3) 15
(44.1) 4 (25) Radiographic
abnormalities Infiltrates
46 (36.8) 1 (31.8)
12 (35.3) 8 (50) Nodules
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(22.4) 21 (31.8) 10 (29.4)
3 (18.7) Cavitation
13 (10.4) 11 (16.7)
13 (38.2) 1 (6.2) Nonspecific
4 (35.2)
19 (28.8) 4 (11.7) 7
(43.7) No symptoms
35 (28) 22 (33.3) 10 (29.4)
0 (0) Data are presented as n,
mean (range) or n (), unless otherwise stated.
MAC Mycobacterium avium-intracellulare complex
M. xenopi Mycobacterium xenopi M. Adapted from
Dailloux et.al. Eur.Respir.J.,2006281211
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AIDS related MAC

• CD4 less than 70
• Hectic chronic fever, GI complaints, esp. with
  very high alkaline phosphatase or severe anemia
• Blood culture slow, insensitive other secretions
  not specific
• Can be pulmonary like with COPD
• Antibiotics without antiretrovirals often
  insufficient

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MAC

• M. avium complex includes M. intracellulare,
  other clinically insignificant ones
• By far main MOTT in AIDS
• 4 types in relatively competent hosts
• 1) fibrocavitary COPD, etc.
• 2) fibronodular older women,
• collagen
  defect
• 3) cystic fibrosis
• 4) hypersensitivity (hot tub)
  pneumonitis

Presumed by assoc. with mitral valve prolapse,
scoliosis,joint hypermobility,pectus excavatum
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Fibronodular MAC with bronchiectasis
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TreeinBud Appearance of Mycobacterial
Pneumonitis
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Rx of MOTT

• Very little correlation or predictive data from
  susceptibilty testing except for
• M.kansasii - rifampin
• MAC clarithromycin
• M.chelonei, fortuitum, abscessus per
  mics
• None susceptible to PZA
• Susceptible to macrolides, amikacin imipenem
  often
• quinolones
• M. abscessus- need IV drug
• 2 and usually 3 drugs preferred
• Duration varies usually at least 1- 11/2 year
  after sputum
• smears turn negative
• Patients without prescription coverage may not be
• treatable

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Risk Factors for TB

• EtOH
• Head/Neck, hematologic cancers
• Silicosis
• HIV - roughly 1 in 14 TB cases have HIV
• Medications-transplant, corticosteroid, TNF
  inhibitors
• Gastrectomy
• Fe excess, Vit D deficiency
• ESRD, DM( Hb A1c gt 7)
• Celiac Disease
• Age

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Acid-Fast Staining Limitations

• Non-mycobacterial bacteria can stain positive
• Smear-positive respiratory secretion implies
• contagious individual
• Approximately 50 sensitive (sputum)
• 3, (and possibly only 1 if suspicion low) sputa
• rules out contagion but NOT active disease
• If AFB () respiratory specimen is negative for
• TB by PCR -TB ruled out, () smear due to
  MOTT

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Pathogenesis of TB

• Anatomic event

• Clinical event

• Granuloma forms to contain walls off, creates
  environment not condusive to growth
• Granuloma enlarges, ruptures into bronchus,
  artery etc.
• Liquefaction of granuloma, extracellular growth,
  inflammatory response lead to necrosis of
  parenchyma

• Calcified lesion (eventually) seen on xray
• Miliary, endobronchial spread (ARDS,
  hypersensitivity pneumonitis), late
  extrapulmonary disease
• Cavitary pneumonia

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TB Miliary, Extra-Pulmonary Disease

• Non specific symptoms may dominate miliary or
  disseminated TB
• Psoas abscess, with or without vertebral
  osteomyelitis, CNS disease relatively common
• May occur with or without active pulmonary disease

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Extra- Pulmonary TB
CID 2009,491350
Excludes disseminated or concurrent
pulmonary/extra pulmonary disease
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Dx. Of TB

• PPD very limited role in dx of active disease
  due to high rate of false (-) and true - but
  unrelated phenomenon
• Can help in CNS disease, pericarditis
• Definition of () PPD depends on circumstances
  (size, prior tests, host etc.)
• Prior BCG must assume positive skin test could
  be due to subsequent TB infection
• Interferon based assays M.tb specific immune
  response to TB proteins, identifies PPD reaction
  as TB rather than MOTT, more sensitive than PPD
  for screening, less for active disease

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Reading TST Result

• Read 4872 hrs after placement
• If HCW returns after gt72 hrs, place and read
  another TST
• Do not let HCWs read their own results
• Find and measure induration
• Measure diameter of induration across the arm
• Do not measure redness

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Positive PPD Interpretation
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Criteria for Initiating Respiratory Precautions

• Patient has symptoms or signs of TB disease
• Or
• Patient has documented infectious TB disease and
  has not completed anti-TB treatment
• Or
• HIV and unexplained respiratory sign/symptom

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General Points on Tb Rx

• INH resistance alone does not affect efficacy of
  standard 4 drug regimen
• Rifabutin preferred over rifampin in HIV
• Extra pulmonary TB Rx 1 year
• 2 or more new/active agents for suspected/proven
  resistance
• Steroids for meningitis, pericarditis, ARDS

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Rx. of TB

• Standard regimen for all unless
• -Suspected resistance ( foreign born,
  failed
• prior Rx)
• -Pregnancy, coexistent liver disease,
  drug
• interaction concerns, intolerance
• Direct observed Rx when possible
• Some strains not treatable

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Immune Reconstitution Inflammatory Syndrome (IRIS)

• Occurs in setting of immune system recovery,
  usually AIDS and initiation of HAART
• Exuberant or poorly coordinated reactions to
  antigen, probably larger amount than usually seen
  in less compromised hosts
• Usually mycobacteria, Cryptococcus or CMV
  retinitis
• High fever, lymphadenitis, or paradoxical
  worsening of primary lesion
• Can be worse than initial presentation

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Summary

• Mycobacteria like lung and lymphatics and weak
  cell mediated immunity causing subacute to
  chronic granulomatous infection
• MOTT also like skin and anatomically abnormal
  lungs, TB likes CNS, vertebrae
• Patients with MOTT usually less ill
• Size and circumstance matter for PPD
• Imaging cant distinguish MOTT vs TB
• Rx requires 2 or more drugs for gt6 months, guided
  by MICs