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Clinical Features of Infections Due to Nontuberculous Mycobacteria

Clinical Features of Infections Due to Nontuberculous Mycobacteria. E. Tortoli. Cesme – Symposium of Mycobacteriology, December 10, 2004. 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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Clinical Features of Infections Due to Nontuberculous Mycobacteria

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  1. Clinical Features of Infections Due to Nontuberculous Mycobacteria E. Tortoli Cesme – Symposium of Mycobacteriology, December 10, 2004

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

  3. Diseases due to NTM • Pulmonary infections • Lymphonodal infections • Cutaneous infections • Osteo-articular infections • Disseminated infections • Sepsis

  4. 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 <100/mL • Symptoms: cough, fever, weight loss

  5. Agents of pulmonary diseases • M. avium complex • M. kansasii • M. xenopi • M. malmoense • “new mycobacteria” • M. celatum • mainly in AIDS with CD4 <100/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

  6. M. xenopi: TB-like pulmonary infiltrates (X-ray) 61-year male Hodgkin’s lymphoma in the past

  7. M. xenopi: TB-like pulmonary infiltrates (CT scan) 61-year male Hodgkin’s lymphoma in the past

  8. M. intracellulare: upper lobe pulmonary infiltrate 67-year, female previously healthy

  9. M. avium: massive upper mediastinum adenopathy (CT scan) 41-year, male AIDS

  10. 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

  11. Agents of cervical lymphadenitis • M. scrofulaceum, classically consideredthe 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

  12. 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

  13. 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)

  14. M. abscessus: painful red nodular lesions of the forearm 45-year, male kidney transplanted aquarium-lover

  15. 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

  16. 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

  17. 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

  18. 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 <25 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

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

  20. Rare NTM-related diseases • Genital infections • Hepatic infections • Ocular infections

  21. 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

  22. 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

  23. 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

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