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

E. Tortoli

Clinical Features of Infections Due to Nontuberculous

Mycobacteria

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

Diseases due to NTM

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

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

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

M. xenopi: TB-like pulmonary infiltrates (X-ray)

61-year maleHodgkin’s lymphoma in the past

M. xenopi: TB-like pulmonary infiltrates (CT scan)

61-year maleHodgkin’s lymphoma in the past

M. intracellulare: upper lobe pulmonary infiltrate

67-year, femalepreviously healthy

M. avium: massive upper mediastinum adenopathy (CT scan)

41-year, maleAIDS

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

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

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

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)

M. abscessus: painful red nodular lesions of the forearm

45-year, malekidney transplantedaquarium-lover

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

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

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

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

Sepsis

Several cases of catheter-related sepsis have been reported for rapidly growing mycobacteria

M. immunogenum (bone marrow transplantation, leukemia, pacemaker holder)

Rare NTM-related diseases

Genital infectionsHepatic infectionsOcular infections

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

Conclusions 2

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

drug susceptibility

Conclusions 3

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

the ATS criteria