Overview of non-tuberculous mycobacteria
Non-tuberculous mycobacteria (NTM) are mycobacteria in the genus Mycobacterium, with the exception of the Mycobacterium tuberculosis complex (Mycobacterium tuberculosis human, Mycobacterium bovis, Mycobacterium africanum, and Mycobacterium vole) and Mycobacterium leprae. It is a conditionally pathogenic bacterium. Diseases caused by NTM are called non-tuberculous mycobacterial diseases.
Causes
NTM are widely distributed in nature in soil, dust, running water and raw milk, while Runyon’s classification divides them into the following four groups:
1. Group I light color-producing bacteria
This group of bacteria tends to cause lung infections, but the condition is mild and the clinical symptoms are similar to those of tuberculosis.
2. Group II dark color-producing bacteria
These bacteria can cause cervical lymphadenitis, pulmonary or extrapulmonary infections and abrasive abscesses in children.
3.Group III non-color-producing bacteria
These organisms can cause lung infections, lymphadenitis, arthritis and meningitis.
4.Ⅳgroup fast-growing bacteria
There are occasional mycobacteria, Mycobacterium avium, Mycobacterium abscessus, Mycobacterium pubescens, etc. The first three species are pathogenic to human beings, and can cause lung diseases and skin infections.
Symptoms
NTM can attack many organs and tissues throughout the body, with the lungs being the most common, and extrapulmonary lesions including lymph nodes, skin, soft tissues and bones.
1. Chronic lung disease
Patients often have a history of chronic obstructive pulmonary disease, tuberculosis, silicosis, lung abscess, bronchiectasis, cystic fibrosis, diabetes mellitus, ulcer disease and application of glucocorticoids, immunosuppressants, more men than women, the symptoms of coughing, coughing up sputum, hemoptysis, chest pain, dyspnea, low-grade fever, lethargy, malaise, but lack of specificity, the condition is slow to progress, the lesions on the X-ray chest radiographs are mostly seen in the right upper lung, showing infiltration, cavities, Nodules, fibrous cheese and extensive fibrous constriction, etc. The incidence of cavities is as high as 80%, single or multiple, and the cavities caused by Mycobacterium intracellulare are mostly located in the subpleural area, with a thin wall and little peripheral exudation.
2. Lymphadenitis
Lymphadenitis caused by NTM is far more common than lymphatic tuberculosis, mostly seen in children under 12 years old, mainly in children aged 2-4 years old, children aged 0-5 years old accounted for the majority, the incidence rate is 10 times higher than that of tuberculous lymphadenitis, children have the habit of playing with mud, the lesions are located in the neck, submandibular, groin, supra-ankle of the humerus, axillary lymph nodes are enlarged, painless, but there may be tenderness, the progression of the slow, lymph node ulceration and formation of sinus tracts, deterioration and improvement repeatedly alternated. The disease alternates repeatedly between worsening and improving, ending in fibrosis and calcification.
3. Meningitis
It is common in patients with AIDS, back trauma and neurosurgery, and its clinical manifestation is quite similar to tuberculous meningitis, but the death rate is higher.
4. Skin and soft tissue infections
Most common in swimming pools, or seawater swimmers skin abrasions, such as elbows, knees, ankles, fingers (toes) at the skin, the beginning of the reddish-brown papules, nodules or plaques, and then soften and ulcerate into superficial ulcers, which can be prolonged for several months or even a few years, but will not form a fistula, and occasionally along the lymphatic vessels in the development of the cardio-centric, the lesions are self-limiting, and the occasional mycobacteria complex can be invaded through the local skin wounds to form a limited abscess, focal cellulitis, mostly medical infection, Mycobacterium ulcerans often cause painless subcutaneous nodules on the lower legs and forearms, followed by the formation of blisters, ulceration leads to necrotic ulcers, the surface covered with yellow necrotic material, the surrounding skin elevated, hyperpigmentation, late mechanized formation of keloid scars can lead to deformity.
5. Skeletal system lesions
It is often infected by wound contact with soil and water, which can cause bone, joint, tendon sheath, bursa and bone marrow infections, and Mycobacterium avium subspecies can cause septic arthritis.
6. Hematogenous disseminated mycobacteriosis
It can be seen in patients with severe cellular immunosuppression, such as hematological malignancy or patients receiving adrenal glucocorticoid therapy and AIDS. Clinical features include long and fluctuating course of the disease, involvement of various systems and organs, resistance to anti-tuberculosis drugs, poor prognosis, high mortality rate, inflammatory changes in lungs, of which 1/4 are cornified changes, and hepatosplenomegaly can be seen.
7. Infection in other parts of the body
There are also Mycobacterium avium intracellulare complex (MAC) causing urinary and reproductive system infections; Mycobacterium avium occasionalis causing eye and dental infections; Mycobacterium linda causing gastrointestinal tract infections.
8. Hospital infections
In recent years, attention has been paid to NTM-induced hospital-acquired infections. It mainly occurs in surgical contamination, interventional therapy contamination, intubation contamination, artificial dialysis contamination and cardiac extracorporeal circulation contamination and other cases of infection.
Examination
1. Bacteriologic examination
For patients suspected of NTM lung disease, sputum smear can be taken for antacid staining, sputum culture, bronchial lavage specimen culture, if antacid staining is positive, it should be cultured and identified, such as 2-3 times culture for the same kind of NTM, it can be diagnosed.
2.Pathologic examination
The pathology of NTM lymphadenitis is characterized by granulomatous inflammation, while tuberculous nodules formed by epithelioid cells and Langhans giant cells are rare and not accompanied by central caseous necrosis.
3. Molecular biology examination
NTM strain identification is accurate, rapid and simple.
4. Mantoux skin test
The diameter of hard nodule of PPD-T in NTM patients usually does not exceed 15 mm. If the diameter of hard nodule of PPD-NTM skin test is 5 mm or more than 25% larger than that of PPD-T skin test, it can be regarded as NTM infection.
5. X-ray examination
The lesions are mostly found in the right upper lung, showing infiltration, cavities, nodules, fibrous cheese and extensive fibrous constriction, etc. The incidence of cavities is as high as 80%, and they are single or multiple.
Diagnosis.
The diagnosis of nontuberculous mycobacteriosis depends on clinical, X-ray and bacterial culture and strain identification, especially the latter, which is the main basis for confirming the diagnosis. According to the Guidelines for the Diagnosis and Management of Non-Tuberculous Mycobacteriosis drawn up by the National Symposium on Atypical Mycobacteriosis in 2000:
1. NTM infection
NTM infection can be diagnosed if there are two conditions at the same time: (1) positive PPD-NTM skin test, (2) lack of evidence that tissues or organs are infected by Mycobacterium tuberculosis.
2. NTM disease suspects
Those who have one of the following conditions are suspected of NTM disease and must undergo NTM examination: ① tuberculosis patients who are ineffective in regular anti-tuberculosis treatment or those whose specimen is still positive in antacid staining; ② those whose specimen is positive in antacid bacillus but the clinical manifestation is not consistent with tuberculosis; ③ those whose specimen is positive for mycobacterium culture but the state of the colonies and their growth are different from those of mycobacterium tuberculosis complex; and ④ those whose mycobacterium has abnormality in microscope examination; (5) The mycobacteria isolated for the first time from patients with primary tuberculosis are resistant to anti-tuberculosis drugs; (6) Lung infections with immunodeficiency, leukemia, tumor and long-term application of immunosuppressant drugs, diabetes mellitus and other lung infections that have been excluded from tuberculosis; (7) Medical or non-medical soft tissue injuries, or wounds that do not heal for a long period of time after surgery cannot be identified as the cause of the problem.
3.NTM lung disease
With respiratory symptoms or with systemic symptoms, lung lesions shown on X-ray chest radiographs, other diseases have been excluded, in order to ensure that the specimen is not contaminated, with one of the following conditions can be diagnosed as NTM lung disease: ① sputum NTM culture of the same NTM bacteria three times; ② sputum NTM culture of the same NTM bacteria twice, one sputum smear stained with positive antacid; ③ bronchial lavage fluid NTM culture positive; ④ Positive NTM culture of bronchopulmonary biopsy material; ⑤ Granuloma similar to NTM lesion is seen in lung biopsy and sputum NTM culture is positive for 1 time.
4. Extrapulmonary NTM disease
NTM lymphadenitis should be distinguished from other bacterial-induced pyogenic lymphadenitis, tuberculous lymphadenitis, cat scratch disease, infectious mononucleosis, etc. PPD-NTM skin test has differentiating value.
Treatment
The general principles of treatment are ① combination; ② adequate dosage; ③ adequate course of treatment (continue treatment for 18-24 months after negative antacids); ④ use rifampicin as much as possible.
1.Drug treatment
(1) Lung infections Pneumonia caused by Mycobacterium avium-intracellulare complex MAIC infection is treated with rifampicin, ethambutol and streptomycin or rifampicin, ethambutol and isoniazid. Those infected with Mycobacterium kansasensis may be treated with a combination of isoniazid, rifampicin, and ethambutol for 18 months, which may be changed to rifabutin, amikacin, and methotrexate for 18 months if the strain is resistant to them. Mycobacterium abscessus lung disease There is no reliable antibiotic dosing regimen to cure Mycobacterium abscessus lung disease to date. Periodic treatment with a multidrug regimen can help control symptoms and the course of lung disease. The dosing regimen consists of a macrolide in combination with one or more intravenous drugs (amikacin, cefoxitin, or imipenem) or multiple non-gastrointestinal medications for several months, such as erythromycin (or azithromycin, or clarithromycin) in combination with ciprofloxacin therapy. If the patient has cavitary/fibro-nodular disease or severe systemic infections, more aggressive (intensive) treatment is indicated, and the recommended regimen is a triple combination of drugs, which may be considered: clarithromycin or azithromycin; rifabutin or rifampicin; and ethambutol.
(2) Lymph node infections Lymph node infections caused by the Mycobacterium avium-intracellulare complex MAIC can be treated with a triple combination of drugs: azithromycin, rifabutin, and amikacin.
(3) Skin and soft tissue infections Soft tissue infections caused by Mycobacterium avium subsp. marinum infection can be treated with doxycycline + sulfamethazine/metronidazole (compound sulfamethazine); or rifampicin + ethambutol. Clarithromycin or azithromycin monotherapy may also be effective. It is also combined with surgical debridement. If caused by Mycobacterium ulcerans infection may be treated with rifampicin, amikacin, or ethambutol, methotrexate, and combined with surgical debridement. Occasional mycobacterial infection to surgical removal of the infection site is the main, at the same time the application of amikacin, cefoxitin, probenecid treatment for 1 month, the new macrolide azithromycin, clarithromycin can also be used. Mycobacterium tuberculosis infection caused by the surgical removal of subcutaneous abscesses at the same time the application of amikacin (or tobramycin), azithromycin (or clarithromycin) treatment, if necessary, can be added with imipenem, the course of treatment is generally 6 months.
(4) Disseminated NTM disease Disseminated NTM disease caused by human immunodeficiency virus (HIV) infection complicated by Mycobacterium kansasii infection can be treated with a combination of ciprofloxacin (or levofloxacin), amikacin, rifabutin, and imipenem; or with azithromycin (or clarithromycin), rifabutin (or rifapentine), clofazimine, and ethambutol.
2. Surgical treatment
Surgical excision can be used as an adjunctive therapy for nontuberculous mycobacterial infections, and is suitable for patients with ineffective or unsuccessful medical treatment and recurrent and intractable hemoptysis. in NTM lymphadenitis, the entire lymph node mass should be excised as far as possible, and if sinus tracts and skin lesions have been formed, the skin lesion area should be excised as well. in NTM skin and soft-tissue infections, extensive surgical excision should be carried out for the skin lesion area in conjunction with drug treatment. Surgical resection is also indicated in cases of NTM lung disease where drug therapy is ineffective, massive excretion of bacteria for more than 1 year, and confined lesions such as cavities in the lungs.