Overview.
Non-tuberculous mycobacteria (NTM) are all mycobacteria other than Mycobacterium tuberculosis and Mycobacterium leprae, also known as environmental mycobacteria. Non-tuberculous mycobacteriosis is a disease of associated tissues or organs caused by infection of humans with NTM, a conditionally pathogenic organism that can colonize the respiratory tract of healthy individuals with certain types of NTM and disappear when oral and respiratory hygiene is improved.
Etiology
Mycobacterium non-tuberculosis is widespread in nature in soil, dust, water, fish and poultry. Transmission is mainly from environmental sources, such as sewage, and human-to-human transmission is rare. These mycobacteria are usually less pathogenic than Mycobacterium tuberculosis in humans, but can cause disease if there are susceptibility factors that cause local or systemic immune dysfunction in the host.
Symptoms
NTM mainly attacks the lungs. Different strains of Mycobacterium species have different sites of prevalence and different clinical manifestations.
1.NTM lung disease
The main strains of NTM are Mycobacterium avium intracellulare complex, Mycobacterium kansasii, Mycobacterium abscessus, and Mycobacterium toadstoolii; it is more common in middle-aged and old men. Clinical manifestations are similar to those of nontuberculous diseases, hemoptysis is common, and patients often have chronic obstructive pulmonary disease, bronchiectasis, or other chronic lung diseases. Chest radiographs show inflammatory foci and single and multiple thin-walled cavities, while fibrosclerotic foci, spherical foci, and pleural exudates are relatively rare. Most of the lesions involve the apical or anterior segments of the upper lobes of the lungs.
2.NTM lymphadenitis
The main strains are Mycobacterium avium intracellulare complex; it is most common in the cervical lymph nodes, and may also involve the ear, groin, and axillary lymph nodes. Mostly unilateral painless lymph node enlargement, often with fistula formation.
3.NTM skin and soft tissue disease
The main strains are Mycobacterium marinum, Mycobacterium occasionalis, Mycobacterium turtle, Mycobacterium abscessus, Mycobacterium ulcerans. Localized abscesses are mostly caused by Mycobacterium occasionalis, Mycobacterium turtle, Mycobacterium abscessus. Mycobacterium marinum can cause swimming pool granulomas and sporotrichosis. Mycobacterium ulcerans can cause Bairnsdale ulcer. Mycobacterium kansasii, Sugar, and Haemophilus can cause disseminated and multicentric nodular lesions of the skin.
4. NTM bone disease
Mycobacterium kansasii and Mycobacterium avium intracellulare complex can cause synovial, bursal, tendon sheath, joint, deep hand, and lumbar vertebral lesions and osteomyelitis; Mycobacterium landis can cause synovitis and osteomyelitis; Mycobacterium secondaryis can cause septic arthritis, whereas Mycobacterium occasionalis and Mycobacterium glabrata often cause dental infections.
5.Disseminated NTM disease
The main strains are Mycobacterium avium intracellulare complex, Mycobacterium kansasii, Mycobacterium abscessus and Mycobacterium haemophilus; they are mostly found in patients with AIDS and other causes of severe immunosuppression. Clinical manifestations include disseminated bone disease, liver disease, endocarditis, pericarditis, and meningitis.
6. Other NTM diseases
For example, Mycobacterium avium intracellulare complex causes genitourinary disease, Mycobacterium occasionalis because of ocular, prosthetic valve and surgical site infections; Mycobacterium abscessus, Mycobacterium marinum, Mycobacterium avium intracellulare complex, Mycobacterium turtle, etc. cause otitis media; Mycobacterium occasionalis, Mycobacterium abscessus, and Mycobacterium turtle cause associated infections have also been reported.
Examination
1. Bacteriologic examination
Smear and culture of sputum and bronchoalveolar lavage fluid are the most common tests. The smear is positive for antacid staining (Ziehl-Neelsen), but the detection rate is low, and it cannot be differentiated from Mycobacterium tuberculosis. Cultures and biochemical tests such as nicotinic acid test, catalase test and aromatic sulfate esterase activity are required.
However, the test results cannot be obtained at an early stage. In recent years, there are some rapid culture and bacillus identification methods that have been clinically applied.
2. Chest X-ray examination
It often shows fibrous nodular shadow in unilateral and bilateral upper lung field, when the disease progresses, the lesion expands and fuses, and the boundary is blurred, and thin-walled cavity appears, the infiltration around the cavity and dissemination of lesions are less, the chronic cavity is thick-walled and honeycomb shadow, and the lesions in the apical segments of the lower lobes of the two lungs are also common. Diabetes mellitus and other immunosuppressed individuals often present with small nodular lesions in the middle and lower fields, and less frequently with pleural effusion. A high-resolution CT scan of the chest provides a clearer visualization of the lung lesions, as well as the accompanying multiple bronchiectasis.
Diagnosis
1. Pathogenetic diagnosis
NTM screening should be routinely performed on TB cultures. Specimens are inoculated with both Roche medium and medium containing p-nitrobenzoic acid (PNB) or thiophene-2-carboxylic acid hydrazide (TCH). If only Roche medium grows, it is Mycobacterium tuberculosis, and if only PNB or TCH medium grows, it suggests NTM and requires further characterization. The addition of NAP (5μg/ml) to Bactec460 systemic medium inhibits the growth of Mycobacterium tuberculosis without inhibiting NTM, and the results are distinguishable.
2.Diagnostic criteria
(1) NTM infection After human infection with NTM, only a very small number of people develop the disease. NTM infection can be diagnosed if the following two conditions are met: (1) positive skin test for NTM; (2) no evidence of invasion of tissues and organs by non-tuberculous mycobacteria.
(2) Suspects of NTM disease focus on those tuberculosis patients who have failed to receive regular anti-tuberculosis treatment. (1) Sputum positive for Mycobacterium avium but clinical manifestations are not consistent with tuberculosis. ② Sputum microscopic examination found mycobacteria with abnormal bacterial bodies. ③ Specimen mycobacterium culture is positive, but its colony morphology and growth are different from that of Mycobacterium tuberculosis complex. ④ Mycobacteria isolated for the first time from first-time tuberculosis patients are resistant to anti-tuberculosis drugs. ⑤ Patients who have received ineffective regular anti-tuberculosis treatment and have repeatedly excreted mycobacteria. ⑥ Those who cannot be negative for sputum mycobacteria after bronchial hygiene purification treatment. (7) Patients with immunodeficiency but with pulmonary disease excluding tuberculosis. (8) Medical or non-medical soft tissue injuries or surgical wounds that do not heal for a long time can not find the cause. With one of the above conditions, that is, NTM disease suspects.
(3) NTM lung disease with respiratory and (or) systemic symptoms, found by radiographic examination of intrapulmonary lesions, has been excluded from other diseases, in order to ensure that the specimen is not exogenous contamination under the premise of one of the following conditions, combined with radiographic and clinical diagnosis of NTM lung disease: ① sputum NTM culture 3 times for the same causative agent. ② Sputum NTM culture 2 times are the same causative organisms, and 1 time antifungal bacillus (AFB) smear positive. ③ Bronchial lavage NTM culture is positive for 1 time and AFB smear is positive (++) or more. ⑤ Positive NTM culture of bronchopulmonary tissue biopsy. (vi) Positive NTM culture of sputum or bronchial lavage fluid for granulomas similar to NTM changes seen in lung biopsy. The diagnosis of extrapulmonary NTM disease can be made when there are localized and/or systemic symptoms, extrapulmonary tissue and organ lesions are found by relevant examinations, other diseases have been ruled out, and the tissue of the lesion site is positive for NTM culture under the premise of ensuring that there is no exogenous contamination of the specimen.
Treatment
1. Mycobacterium avium intracellulare complex
(1) Immunocompetent persons ①Small nodular/bronchodilated lesions: clarithromycin or azithromycin+EMB+RFP. ②Cavitary lesions: clarithromycin or azithromycin+EMB+RFP±streptomycin or amikacin. (iii) Patients with advanced (severe) disease or allergy to the original treatment: same treatment as for cavitary lesions, but remove RFP.
(2) Immunosuppressed (HIV/AIDS) ① Initial prophylaxis: for patients with CD4+ counts less than 50-100 μL. (②Treatment: Clarithromycin+EMB+RFP, oral; alternatively, Azithromycin+EMB±RFP, oral. (iii) Secondary prevention: prevention is necessary. Choose clarithromycin or azithromycin + EMB; alternatively, clarithromycin or azithromycin or RFP.
2. Mycobacterium kansasii
INH+RFP+EMB. If RFP is resistant, choose INH+vitamin B6+EMB, then combine with SMZ-TMP until culture is negative.
3. Mycobacterium toadii
Program is not determined. Trial of macrolides + RFP/RFB + EMB ± SM or RFP + INH + EMB is possible. Recent studies suggest that most patients with HIV infection do not require treatment.
4. Mycobacterium marinum
Surgical resection, occasionally chemotherapy indicated, regimen undefined.
5. Mycobacterium ulcerans
RFP+AMK or FMB+SMZ-TMP. surgical resection is most important.
6. Mycobacterium gordonii
No decision on protocol. Consider RFP+EMB+KM or ciprofloxacin.
7. Mycobacterium haemophilus
Protocol undetermined. Surgical debridement may be required.
8. Mycobacterium marinum
Clarithromycin or minocycline or doxycycline, or SMZ-TMP, or RFP+EMB with surgical resection.
9. Mycobacterium avium
Protocol not determined. Start a 4-drug combination, same as disseminated Mycobacterium avium intracellulare complex.
10. Mycobacterium Geneva
Apply ≥2 drug combinations such as EMB, RFP, RFB, clofazimine, clarithromycin. Ciprofloxacin is not effective.
11. cryptic mycobacteria
Rational regimen not determined. Most use clarithromycin + EMB + ciprofloxacin ± RFP.
12.Mycobacterium avium (abscess subtype and turtle subtype)
Subcutaneous abscess excision combined with chemotherapy, optionally clarithromycin orally. Azithromycin is also effective. Combination of AMK + imipenem or cefoxitin for the first 2 to 6 weeks in severe disseminated cases.
13. Occasional mycobacteria
Ideal regimen not determined. Surgical excision of infected foci. Chemotherapy available (AMK + cefoxitin + probenecid). Oral administration of two sensitive drugs for 6 to 12 months is usually effective. Nail salon acquired infections minocycline, doxycycline, or ciprofloxacin are effective for 4 to 6 months.