Препоръки за диагноза, лечение и превенция на нетуберкулозни микобактериални инфекции

An Official  ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases

 

This  Official Statement of the American Thoracic Society  (ATS)  and the Infectious Diseases Society  of America (IDSA) was  adopted by the ATS Board Of  Directors, September  2006, and by the IDSA  Board of Directors, January 2007

 

SUMMARY

 

Diagnostic Criteria of Nontuberculous Mycobacterial Lung Disease

The minimum evaluation of a patient suspected of nontubercu- lous mycobacterial (NTM) lung disease should include the fol- lowing: (1 ) chest radiograph or, in the absence of cavitation, chest high-resolution computed tomography (HRCT) scan; (2 ) three or more sputum specimens for acid-fast bacilli (AFB) analysis; and (3 ) exclusion of other disorders, such as tuberculosis (TB). Clinical, radiographic, and microbiologic criteria are equally im- portant and all must be met to make a diagnosis of NTM lung disease. The following criteria apply to symptomatic patients with radiographic opacities, nodular or cavitary, or an HRCT scan that shows multifocal bronchiectasis with multiple small nodules. These criteria fit best with Mycobacterium avium complex (MAC), M. kansasii, and M. abscessus. There is not enough known about most other NTM to be certain that these diagnostic criteria are universally applicable for all NTM respiratory pathogens.

Clinical.

1. Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or an HRCT scan that shows multifocal bronchiectasis with multiple small nodules. and

2. Appropriate exclusion of other diagnoses.

 

Microbiologic.

1. Positive culture results from at least two separate expecto- rated sputum samples. (If the results from the initial spu- tum samples are nondiagnostic, consider repeat sputum AFB smears and cultures.) or

2. Positive culture results from at least one bronchial wash or lavage. or

3. Transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histopathologic features (granulomatous in- flammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM.

4. Expert consultation should be obtained when NTM are recovered that are either infrequently encountered or that usually represent environmental contamination.

5. Patients who are suspected of having NTM lung disease but who do not meet the diagnostic criteria should be followed until the diagnosis is firmly established or excluded.

6. Making the diagnosis of NTM lung disease does not, per se, necessitate the institution of therapy, which is a decision based on potential risks and benefits of therapy for individ- ual patients.

 

Key Laboratory Features of NTM

1. The preferred staining procedure is the fluorochrome method. Specimens should be cultured on both liquid and solid media. Species that require special growth con- ditions and/or lower incubation temperatures include M. haemophilum, M. genavense, and M. conspicuum. These species can cause cutaneous and lymph node disease.

2. In general, NTM should be identified to the species level.

Methods of rapid species identification include commercial DNA probes (MAC, M. kansasii, and M. gordonae) and high-performance liquid chromatography (HPLC). For some NTM isolates, especially rapidly growing mycobac- terial (RGM) isolates (M. fortuitum, M abscessus, and M. chelonae), other identification techniques may be nec- essary including extended antibiotic in vitro susceptibility testing, DNA sequencing or polymerase chain reaction (PCR) restriction endonuclease assay (PRA).

3. Routine susceptibility testing of MAC isolates is recom- mended for clarithromycin only.

4. Routine susceptibility testing of M. kansasii isolates is rec- ommended for rifampin only.

5. Routine susceptibility testing, for both taxonomic identifi- cation and treatment of RGM (M. fortuitum, M abscessus, and M. chelonae) should be with amikacin, imipenem (M. fortuitum only), doxycycline, the fluorinated quinolones, a sulfonamide or trimethoprim-sulfamethoxazole, cefoxitin, clarithromycin, linezolid, and tobramycin (M. chelonae only).

Health Care– and Hygiene-associated Disease Prevention

Prevention of health care–related NTM infections requires that surgical wounds, injection sites, and intravenous catheters not be exposed to tap water or tap water–derived fluids. Endoscopes cleaned in tap water and clinical specimens contaminated with tap water or ice are also not acceptable.

 

Prophylaxis and Treatment of NTM Disease

1. Treatment of MAC pulmonary disease. For most patients with nodular/bronchiectatic disease, a three-times-weekly regimen of clarithromycin (1,000 mg) or azithromycin (500 mg), rifampin (600 mg), and ethambutol (25 mg/kg) is recommended. For patients with fibrocavitary MAC lung disease or severe nodular/bronchiectatic disease, a daily regimen of clarithromycin (500–1,000 mg) or azithromycin (250 mg), rifampin (600 mg) or rifabutin (150–300 mg), and ethambutol (15 mg/kg) with consideration of three- times-weekly amikacin or streptomycin early in therapy is recommended. Patients should be treated until culture negative on therapy for 1 year.

2. Treatment of disseminated MAC disease. Therapy should include clarithromycin (1,000 mg/d) or azithromycin (250 mg/d) and ethambutol (15 mg/kg/d) with or without rifabutin (150–350 mg/d). Therapy can be discontinued with resolution of symptoms and reconstitution of cell- mediated immune function.

3. Prophylaxis of disseminated MAC disease. Prophylaxis should be given to adults with acquired immunodeficiency

syndrome (AIDS) with CD4+ T-lymphocyte counts less than 50 cells/,_l. Azithromycin 1,200 mg/week or clarithro-

mycin 1,000 mg/day have proven efficacy. Rifabutin

300 mg/day is also effective but less well tolerated.

4. Treatment of M. kansasii pulmonary disease. A regimen of daily isoniazid (300 mg/d), rifampin (600 mg/d), and ethambutol (15 mg/kg/d). Patients should be treated until culture negative on therapy for 1 year.

5. Treatment of M. abscessus pulmonary disease. There are no drug regimens of proven or predictable efficacy for treatment of M. abscessus lung disease. Multidrug regi- mens that include clarithromycin 1,000 mg/day may cause symptomatic improvement and disease regression. Surgi- cal resection of localized disease combined with multidrug clarithromycin-based therapy offers the best chance for cure of this disease.

6. Treatment of nonpulmonary disease caused by RGM (M. abscessus, M. chelonae, M. fortuitum). The treatment regimen for these organisms is based on in vitro susceptibil- ities. For M. abscessus disease, a macrolide-based regimen is frequently used. Surgical debridement may also be an important element of successful therapy.

7. Treatment of NTM cervical lymphadenitis. NTM cervical lymphadenitis is due to MAC in the majority of cases and treated primarily by surgical excision, with a greater than

90% cure rate. A macrolide-based regimen should be con- sidered for patients with extensive MAC lymphadenitis or poor response to surgical therapy.

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