I. Definition.
Refractory tuberculosis is defined as those with persistent or recurrent positive sputum bacteria after more than two years of anti-tuberculosis treatment.
II. Etiology.
(a) After anti-treatment of pulmonary tuberculosis, drug resistance is a serious problem, at least to three or more of the major anti-tuberculosis drugs such as S, H, R, E, Z, P, or all of them.
(ii) Toxic side effects of TB drugs leading to irregular medication and resulting in refractory treatment.
(iii) The presence of coexisting diseases (psychosis, diabetes, silicosis, liver disease, pregnancy and childbirth lactation, epilepsy, peptic ulcer, adrenocorticotropic hormone application, etc.) and comorbidities (hemoptysis, pneumothorax, respiratory failure and heart failure) make TB patients ineffective, resulting in chronic rejection and refractory treatment.
(d) Tuberculosis patients are not managed during anti-tuberculosis treatment and develop refractory to treatment.
(e) Some patients with tuberculosis are asymptomatic or asymptomatic at the beginning, resulting in a delay in detection and a more serious lesion (extensive lesion and cavity) at the time of diagnosis.
(f) Individual patients are older (>60 years old), with poor body resistance and reduced immune function, especially low cellular immune function, making anti-tuberculosis treatment difficult to achieve results and making it difficult to treat.
(vii) Individual patients with immunodeficiency diseases, combined with pulmonary tuberculosis, are prone to refractory; such patients are also called “unresponsive tuberculosis”.
Symptoms and signs.
(a) Symptoms.
1. Systemic tuberculosis toxicity symptoms: low fever in the afternoon, high fever when the lung lesions spread, emaciation, weakness, loss of appetite, anemia, night sweats, menstrual disorders or amenorrhea in female patients; toxicity symptoms such as fever in unresponsive tuberculosis may not be obvious.
2, respiratory symptoms: cough, coughing a small amount of white mucous sputum or dry cough, sputum blood or hemoptysis, shortness of breath and chest tightness, chest pain.
(ii) Physical signs.
Body temperature below 38, but can also be as high as 39-40, tracheal displacement, collapse of the thoracic gallery, narrowing of the rib space, turbid percussion, diminished breath sounds, dry and wet rales, or no obvious pathological signs.
IV. Examination
(A) Bacteriological examination: sputum smear and drug sensitivity test, bacteriological identification, L-type bacteria and PCR examination if necessary.
(B) X-ray examination: frontal and lateral chest radiographs, body layer or chest CT if necessary, to facilitate local treatment.
(c) Blood, urine and stool routine, blood sedimentation, liver function, blood glucose and urine sugar, and glucose tolerance test if necessary. Hepatitis B markers (HBVm), renal function, pulmonary function, electrocardiogram, etc.
(iv) Examination during treatment: sputum smear 3 times a month, liver function once a month, blood, urine routine, blood sedimentation, etc. when necessary.
(E) Determination of blood concentration of anti-tuberculosis drugs to guide the use of drugs.
(vi) PPD test and necessary immunological and pathological examinations.
V. Diagnosis
1.Anti-tuberculosis treatment for more than two years, but sputum bacteria are still persistently or repeatedly positive.
2.Serious drug resistance problem, at least to S.H, R, Z, E, P and other major anti-tuberculosis drugs three or more resistant or all resistant.
(B) Typing and staging (see the relevant sections on tuberculosis typing and staging).
Differential diagnosis
Refractory tuberculosis is mainly distinguished from nontuberculous mycobacteriosis.
VII. Treatment
(a) General treatment: strengthen nutrition, pay attention to physical rest, and improve the body’s ability to resist.
(2) Symptomatic treatment: cough expectoration, application of hemostatic drugs in case of hemoptysis, application of antipyretic drugs in case of fever, oxygen absorption and sputum aspiration when necessary, etc., all see relevant chapters.
(C) Anti-tuberculosis treatment.
1.Drug treatment.
(1) First, according to the history of drug use, select the main anti-tuberculosis drugs that are not used or used sparingly, or new anti-tuberculosis drugs, or new anti-tuberculosis drugs in combination with 2-3 kinds of treatment.
(2) Select the main or alternate anti-tuberculosis drugs that are still sensitive according to the drug sensitivity test and combine them with no less than two new sensitive drugs.
(3) The intensive treatment period should be extended to 3 months, and to 4 months for those who are still positive at the end of 3 months, and the total treatment period should be 8-12 months or longer.
(4) Change the route of administration.
(1) Intravenous administration: H, P, K, DK, OFX can be administered intravenously.
(2) Local administration: anti-tuberculosis drugs can be injected into the cavity wall via nasal cannula, fibrinoscopy, nebulized inhalation or through the chest wall.
③Increase the drug dose: for example, change H to 400-600mg/d, P to 12-18g/d and R to 600mg/d under the condition of monitoring liver function and under the guideline of blood concentration measurement.
④ Combined application of immune enhancement with herbal preparations: interleukin TB-specific transfer factor, euforin, tuberculosis spirit, rejuvenation, cat’s claw, etc.
⑤ Proper management of coexisting diseases of TB (diabetes, silicosis, liver disease, psychosis, adrenal cortical dysfunction, peptic ulcer and pregnancy, etc.).
⑥Management of complications: hemoptysis, pneumothorax, respiratory failure, heart failure and co-infection, etc. (all see relevant chapters).
(7) Patient management: hospitalization or monitoring during the intensive period, full management or follow-up management during the continuation period.
2.Surgical treatment
Resistant to more than three drugs, lesions limited to one lobe or one side of the lung function is still possible, MBC > 70% of the expected value, should strive for early surgical resection.