E. Tortoli

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Clinical Features of Infections Due to
Nontuberculous Mycobacteria

• E. Tortoli

Cesme Symposium of Mycobacteriology, December
10, 2004
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Nontuberculous mycobacteria

• Environmental
• Opportunistic
• About 3 new species per year
• Over 100 species, 60 of which described in the
  last 15 years

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Diseases due to NTM

• Pulmonary infections
• Lymphonodal infections
• Cutaneous infections
• Osteo-articular infections
• Disseminated infections
• Sepsis

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Pulmonary disease

• The most frequent NTM disease with the main route
  of infection being the inhalation
• HIV-negative patients
• Disease undistinguishable from tuberculosis,
  very slow progression
• manifestations ranging from lack of symptoms to
  cavitary disease
• radiographic picture presenting fibrosis, upper
  lobe cavitation, nodular or parenchymal opacity,
  pleural thickening
• Target elderly patients with other pulmonary
  problems (silicosis, OPD, pneumoconiosis,
  previous TB, bronchiectasis, cancer)
• Symptoms cough, fever, weight loss, weakness,
  respiratory insufficiency
• AIDS patients
• Disease chest X-ray often normal or presenting
  mediastinal / hilar adenopathy, rapid progression
• Target patients with CD4 lt100/mL
• Symptoms cough, fever, weight loss

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Agents of pulmonary diseases

• M. avium complex
• M. kansasii
• M. xenopi
• M. malmoense
• new mycobacteria
• M. celatum
• mainly in AIDS with CD4 lt100/mL
• rifampicin resistant
• possible misdiagnosis as M. tuberculosis
• M. goodii from patients with lipoid pneumonia
• M. immunogenum isolated from aerosols of
  metal-working fluids which are associated with
  hypersensitivity pneumonitis

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M. xenopi TB-like pulmonary infiltrates (X-ray)
61-year male Hodgkins lymphoma in the past
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M. xenopi TB-like pulmonary infiltrates (CT scan)
61-year male Hodgkins lymphoma in the past
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M. intracellulare upper lobe pulmonary
infiltrate
67-year, female previously healthy
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M. avium massive upper mediastinum adenopathy
(CT scan)
41-year, male AIDS
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Lymphadenitis

• Scrofula disease of childhood, exceptional in
  adults
• Unilateral swelling of cervical lymph nodes
  without pain and without thoracic involvement
• Evolution with softening and fistula formation
• Oral route of infection including throat,
  gingivae and lips
• Surgical treatment, antimicrobial therapy
  ineffective

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Agents of cervical lymphadenitis

• M. scrofulaceum, classically considered the main
  responsible of scrofula
• M. avium complex, the current most frequent agent
  of NTM lymphadenitis
• M. malmoense
• new mycobacteria
• M. bohemicum
• M. interjectum
• M. lentiflavum
• A number of pigmented slow growing new species

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Disease of skin and soft tissue

• Consequent to trauma or surgical wound (mainly
  plastic or cardiac interventions)
• Nodular granulomatous lesions of cutis or
  subcutaneous developing in about a month and
  often involving lymph nodes
• Frequent dissemination with ulcer formation or
  cellulitis
• Almost only rapidly growing species involved

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Agents of skin and soft tissue infections

• M. abscessus
• M. chelonae
• M. fortuitum
• M. smegmatis
• new mycobacteria
• M. goodii (following pacemaker implantation and
  breast plastic interventions)
• M. mageritense (following liposuction)
• M. wolinskyi (following facial plastic surgery
  and responsible of post traumatic cellulitis)

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M. abscessus painful red nodular lesions of the
forearm
45-year, male kidney transplanted aquarium-lover
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Bone and articular infections

• Targets synovia, tendon sheaths, bursa, bone
  tissue, vertebral discus
• Consequent to open fracture, penetrating trauma
  or surgical wound (mainly cardiac)
• Possible evolutions lost of function, swelling,
  fistula or granuloma formation, osteomyelitis
  and/or cellulitis, bone necrosis
• Predisposing conditions chronic rheumatism and
  steroid treatment

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Agents of bone and articular infections

• M. abscessus
• M. chelonae
• M. fortuitum
• M. smegmatis
• new mycobacteria
• M. goodii many cases of osteomyelitis and/or
  cellulitis in young people with open fractures or
  penetrating trauma
• M. wolinskyi

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Disseminated infections

• Target immunocompromised patients
• AIDS, leukemia, organ transplantation, protracted
  steroid treatment
• Symptoms fever, weight loss, abdominal pain,
  splenomegaly, diarrhea
• Very frequent several years ago, their role has
  been scaled down following the introduction of
  HAART

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Agents of disseminated infections

• M. avium estimated to affect more than 50 of
  severely immunocompromised AIDS patients not
  treated with HAART
• M. genavense
• Young subjects, prevalently male, with lt25 CD4/mL
• Isolated predominantly from blood but also from
  lymph nodes and duodenal biopsies
• Extremely rare in HIV-negative patients
• M. celatum
• Responsible of disseminated infections combined,
  or not, with pulmonary disease

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Sepsis

• Several cases of catheter-related sepsis have
  been reported for rapidly growing mycobacteria
• M. immunogenum (bone marrow transplantation,
  leukemia, pacemaker holder)

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Rare NTM-related diseases

• Genital infections
• Hepatic infections
• Ocular infections

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Conclusions 1

• In AIDS patient the large majority of the
  mycobacterial infections are disseminated, their
  number has dramatically decreased following the
  introduction of HAART
• In HIV-negative subjects
• Slowly growing mycobacteria are prevalently
  responsible of pulmonary and lymphonodal disease
• Rapidly growing mycobacteria are prevalently
  responsible of cutaneous, osteo-articular and
  septic diseases
• The number of cases due to new mycobacteria is
  certainly underestimated because of the
  problematic identification of these strains
• The role of rapid growers is more important than
  commonly believed

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Conclusions 2
drug susceptibility

• Slowly growing mycobacteria
• Isoniazid and pirazinamide are not effective
• Aminoglycosides, quinolones, macrolides,
  rifamycins may be effective
• M. celatum is rifampin-resistant
• The species genetically related to M. simiae are
  dramatically multidrug-resistant
• Rapidly growing mycobacteria
• The spectrum of potentially active drugs
  includes amikacin, cefoxitin, ciprofloxacin,
  clarithromycin, trimetoprim-sulfametoxazole,
  doxycycline, imipenem

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Conclusions 3
the ATS criteria

• Minimal requirements for diagnosing a pulmonary
  infection due to NTM
• Case 1. Three samples have been investigated in
  the last year
• 3 cultures are positive, even with negative
  microscopy
• 2 cultures are positive, at least one of which
  with positive microscopy
• Case 2. One sample only has been investigated
• Culture and microscopy are strongly positive
• Case 3. The involvement in the disease of an
  agent other than a NTM cannot be excluded
• The NTM has been grown from a biopsy
• The histologic picture is compatible with a
  mycobacterial infection and the isolation (even
  single and with low charge) has been obtained
  from the sputum