★ How long can you see that the shadow on the chest radiograph of tuberculosis is obviously absorbed?

Anti-tuberculosis chemotherapy plays a decisive role in the control of tuberculosis, and reasonable chemotherapy can sterilize and cure all the lesions. Traditional rest and nutrition therapy only play an auxiliary role.

First, anti-tuberculosis drug therapy (referred to as chemotherapy)

(1) Principles of chemotherapy From an epidemiological point of view, the main function of chemotherapy is to shorten the infection period of tuberculosis and reduce the mortality, infection rate and prevalence rate. For every patient, it is the main measure to achieve clinical and biological cure. Rational chemotherapy refers to the principle of early, combined, appropriate, regular and full-course use of sensitive drugs for active pulmonary tuberculosis. Clinical symptoms of tuberculosis toxicity, sputum positive, X-ray lesions with inflammatory components, or lesions in the stage of progress or improvement, are all active tuberculosis and are indications of chemotherapy. Long-term induration does not require chemotherapy. For some patients with induration and negative sputum bacteria, clinical observation can be carried out for a period of time. If sputum bacteria are still negative, X-ray shows that the focus is inactive and there are no obvious symptoms of tuberculosis poisoning, so chemotherapy is not necessary.

1. Early, combined, moderate, regular, whole course medication, active lesions are in exudation stage, or caseous necrosis, or even cavity formation. Mycobacterium tuberculosis in the focus is mainly group A bacteria, which grow vigorously and metabolize vigorously. The biggest function of anti-tuberculosis drugs can be sterilization or bacteriostasis. At this time, the local blood vessels of the focus are rich, and the drug concentration is also high, which can make the inflammatory components absorb, the cavity shrink or close, and the sputum bacteria turn negative. Therefore, reasonable chemotherapy for active lesions in the early stage can achieve satisfactory results.

Experiments show that there are about106-10/0 mycobacterium tuberculosis in every 1g caseous lesions or cavities in the lung. Mycobacterium tuberculosis, which has never been exposed to anti-tuberculosis drugs, is not completely consistent in drug sensitivity. About every 105- 106 strains of mycobacterium tuberculosis, 1 strain is resistant to isoniazid or streptomycin due to cell mutation. At the same time, among 10 1 mycobacterium tuberculosis, only 1 is resistant to both drugs, and even fewer bacteria are resistant to three drugs. It can be seen that if only one drug is used for treatment, most sensitive bacteria can be eliminated, but a few drug-resistant bacteria will be left to continue to multiply, and finally drug-resistant bacteria will breed. However, if two or more drugs are used together, the effect is better than that of single drug treatment because there are few drug-resistant bacteria.

The dosage should be appropriate. Insufficient dose can not reach the effective concentration of drugs in tissues, the curative effect is not good, and bacteria are prone to secondary drug resistance. Drug abuse or excessive dosage will not only cause waste, but also easily produce toxic and side effects. Tuberculosis grows slowly, and some only multiply occasionally (flora B and C), so the drug should stay in the body for a long time. Regular medication is used throughout the course, but early withdrawal is an important key to the success of chemotherapy. It should be carried out in strict accordance with the time and interval specified in the chemotherapy plan (such as 1 time/day or 3 times/week) to avoid omission or interruption. Insufficient course of treatment makes the treatment incomplete and increases the recurrence rate. Adhering to the rational use of drugs throughout the course can generally make the sputum negative conversion rate reach more than 95%, the recurrence rate is less than 2% after five years of drug withdrawal, and the mortality rate is obviously reduced. Reasonable chemotherapy can be followed up regularly in outpatient department. By reducing the source of infection, the epidemic of tuberculosis has been controlled.

2. Only when the drug concentration in the blood of the drug and tuberculosis bacteria (including macrophages) is less than 10 times of the minimum inhibitory concentration (MIC) in the test tube under the conventional dose can it play a bactericidal role, otherwise it will only play a bacteriostatic role. The conventional doses of isoniazid and rifampicin can meet this requirement both inside and outside the cell. It's called a full bactericide. Streptomycin and pyrazinamide are also fungicides, but streptomycin can play its greatest role in alkaline environment, and rarely penetrates into phagocytes, which is ineffective against intracellular tuberculosis; Pyrazine amide can penetrate into phagocytes and has bactericidal effect only in acidic environment. Therefore, these two drugs can only be used as semi-fungicides. Ethambutol, p-aminosalicylic acid, etc. They are all bacteriostatic agents, and the conventional dose of these drugs can not reach more than 10 times of MIC in vivo, and its dose can not be increased due to toxic and side effects.

Mycobacterium tuberculosis in the early stage of the disease is mostly extracellular bacteria, and isoniazid has the strongest bactericidal effect at this time, followed by streptomycin. Inflammation lowers the local PH value of tissues, slows down bacterial metabolism (flora C), and is sensitive to rifampicin and pyrazinamide, plus some mycobacterium tuberculosis (flora B) swallowed by cells. Killing these residual bacteria (B and C flora) can reduce the recurrence in the future.

(2) Chemotherapy methods

1. "Conventional" chemotherapy and short-term chemotherapy In the past, isoniazid, streptomycin and sodium p-aminobenzoate were routinely used to treat pulmonary tuberculosis 12- 18 months, which was used to be called "conventional therapy". However, because the course of treatment is too long, patients often cannot persist in the whole course, which affects the curative effect. Since the invention of rifampicin, the effect of chemotherapy has been greatly improved. At present, the combination of isoniazid and rifampicin has strong sterilization (for flora A) and sterilization (for flora B and C), which can shorten the course of treatment to 6-9 months (short-term chemotherapy), and the curative effect (sputum negative conversion, focus absorption) and recurrence rate are as satisfactory as "conventional chemotherapy".

2. Intermittent and two-stage drug administration experiments show that the growth of Mycobacterium tuberculosis is delayed for several days after several hours of contact with drugs. So taking medicine regularly (intermittently) three times a week can achieve the same effect as taking medicine every day. Within 1-3 months after chemotherapy, the effect of daily medication (intensive period) and intermittent medication three times a week (consolidation period) is the same as that of daily medication, and the side effects and drug costs are reduced because of the reduction of drug administration times, which is also convenient for patients, conducive to supervising medication and ensuring the whole process of chemotherapy. Intermittent drug therapy should also be combined with drugs three times a week, and the dosage of isoniazid, rifampicin and ethambutol can be appropriately increased each time; However, some drugs (such as streptomycin, sodium p-aminosalicylate, ethionine, etc. ) Doses should not be increased every time because of their great side effects (Table 2-9-2).

3. Supervise the use of anti-tuberculosis drugs for at least half a year, sometimes as long as one and a half years, and patients often cannot persist. It is important for medical staff to supervise medication on time, strengthen visiting education and obtain patient cooperation. In the intensive period, once daily administration of rifampicin, isoniazid, pyrazinamide, streptomycin and ethambutol can form the peak of blood concentration, which is better than divided daily administration, which is convenient for patients and improves the compliance rate and effect of patients.

Table 2-9-2 Adult Doses and Main Side Effects of Commonly Used Anti-TB Drugs

The main side effects of daily dose (G) sterilization mechanism are peripheral neuritis caused by isoniazid H, INH0.30.6-0.8DNA synthesis, incidental liver function damage caused by rifampicin R, liver function damage caused by RFP0.45-0.6*0.6-0.9mRNA synthesis, streptomycin S allergic reaction and SM 0.75-0./kloc. Kloc-0/ protein synthesis pyrazinamide Z, PAS allergic reaction, liver function damage, isoniazid1321Th0.5-0.750.5-1.0 protein synthesis, gastrointestinal discomfort, liver function damage, kanamycin K, KM 0.75-/Kloc-.

* weight < < 50kg with 0.45, ≥ 50kg0.6; The dosage of s, z and Th is also adjusted according to body weight; △0.75g； Every time it is for the elderly; * * 25 mg/kg in the first two months; Later it was reduced to 15mg/kg. * * * Take it twice a day (all other medicines are once a day).

(3) Anti-tuberculosis drugs Ideal anti-tuberculosis drugs have sterilization, disinfection or strong bacteriostatic effects, low toxicity, few side effects, convenient use, low price and sufficient drug sources; After oral administration or injection, the drug can reach an effective concentration in the blood and penetrate into phagocytes, serous cavity and cerebrospinal fluid, with rapid and lasting curative effect. Commonly used drugs are isoniazid, rifampicin, pyrazinamide, streptomycin, sodium p-aminosalicylate and so on. Here are the main anti-tuberculosis drugs.

1. isoniazid (h) has the advantages of strong bactericidal power, oral administration, few side effects and low cost. It can inhibit the synthesis of mycobacterium tuberculosis deoxyribonucleic acid (DNA) and hinder the synthesis of cell wall. After oral administration, it can be absorbed quickly, penetrate into tissues, cross the blood-brain barrier, and kill the continuously reproducing or nearly static mycobacterium tuberculosis with active metabolism inside and outside cells. The concentration of drugs in pleural effusion, caseous lesions and cerebrospinal fluid is also high. Dosage: 300 mg per day (or 4-8 mg/kg per day) for adults, once orally; Children's daily 5- 10 mg/kg (no more than 300mg per day). The dose of tuberculous meningitis and acute miliary tuberculosis can be doubled (peripheral neuritis can be complicated with increased dose, which can be prevented by vitamin B6; However, a large dose of vitamin B6 will also affect the curative effect of isoniazid, so the general dose of isoniazid does not need to be added with vitamin B6). After the symptoms of acute poisoning are relieved, the routine dose can be changed back. Isoniazid can be administered intratracheal or intrapleural. Isoniazid is inactivated by acetylation in vivo. The speed of acetylation varies from person to person. The plasma concentration of patients with rapid acetylation is low, so it is considered that the dose should be increased intermittently.

The conventional dosage of the drug rarely produces side effects, such as peripheral neuritis, central nervous system poisoning (inhibition or excitement), liver damage (elevated serum alanine aminotransferase) and so on. After only using this drug for 3 months, the drug resistance rate of sputum bacteria was 70%.

2. Rifampicin (R) is a semi-synthetic derivative of rifamycin and a broad-spectrum antibiotic. The mechanism of killing mycobacterium tuberculosis is to inhibit the RNA polymerase of bacteria, thus hindering the synthesis of mRNA. This drug has an effect on mycobacterium tuberculosis (flora A, B and C) which is metabolized vigorously inside and outside the cell and occasionally reproduces, and is usually used in combination with isoniazid. Adults take 450-600 mg orally every day on an empty stomach/kloc-0. The side effects of this drug are very mild, including digestive tract discomfort and influenza syndrome, and sometimes there are temporary liver damage, elevated transaminase and jaundice. In recent years, some long-acting rifampicin derivatives have come out one after another. For example, rifapentine (DL473, rifapentine) has a long half-life in human body, so it is taken orally once a week, and the curative effect is similar to that of taking rifampicin every day. Spiropyridine ansamycin (LM427, using Butin) has a stronger effect than rifampicin on some strains that are ineffective against other anti-tuberculosis drugs (such as Mycobacterium avium-intracellular complex).

3. Pyrazine amide (Z) can kill phagocytes and mycobacterium tuberculosis in acidic environment. Dosage: 65438+ 0.5g daily, taken orally for 3 times. Side effects include hyperuricemia, joint pain, gastrointestinal reaction and liver injury.

4. Streptomycin (S) is a broad-spectrum aminoglycoside antibiotic, which has bactericidal effect on Mycobacterium tuberculosis, can interfere with the enzyme activity of Mycobacterium tuberculosis and hinder the synthesis of protein. It has little effect on intracellular tuberculosis. Dosage: intramuscular injection for adults daily 1g (0.75g for those over 50 years old or with impaired renal function). Intermittent therapy twice a week, each intramuscular injection1g. Pregnant women should use it with caution.

5. Ethambutol (E) has bacteriostatic effect on Mycobacterium tuberculosis, and when it is combined with other anti-tuberculosis drugs, it can delay the emergence of bacterial resistance to other drugs. Dosage: 25mg/kg, once a day 1 time, and changed to one day 15mg/kg after 8 weeks, with few side effects as its advantage. Sometimes there will be gastrointestinal discomfort. Excessive dose can cause retrobulbar optic neuritis, decreased vision, narrowed visual field, central blind spot, red-green blindness and so on. , can be recovered after stopping the drug.

6. Sodium p-aminosalicylate (P) is an antibacterial drug, which can be used together with streptomycin, isoniazid or other anti-tuberculosis drugs to delay drug resistance to other drugs. Antibacterial effect may compete with para-aminobenzoic acid (PABA) in the process of folic acid synthesis in tuberculosis, thus affecting the metabolism of tuberculosis. Dosage: Adults take 8- 12g daily, divided into 2-3 times. Side effects include loss of appetite, nausea, vomiting and diarrhea. In severe cases, the drug should be stopped. The medicine can relieve gastrointestinal reaction after meals, or it can be taken orally after adding 50 ml of 5%- 10% glucose solution every day for 1 month.

(4) The choice of chemotherapy scheme should be based on the severity of the disease, the presence or absence of sputum bacteria and bacterial drug resistance, as well as economic conditions and drug supply. There are various chemotherapy schemes. At present, there are many anti-tuberculosis drugs, and new drugs are constantly emerging. No matter which scheme, it can only be effective if it conforms to the above principles of chemotherapy. Here are some examples.

1. In the newly treated cases without anti-tuberculosis drugs, some sputum smears are positive for tuberculosis (smear positive), which is generally serious and highly contagious; Some smears are negative and the lesion range is not large; The chemotherapy regimens used are also different.

The initial smear positive cases, regardless of whether the culture is positive or not, can be shortened by a 6-month plan based on the combination of isoniazid (H), rifampicin (R) and pyrazinamide (Z). Sputum bacteria often turn negative quickly, and the course of treatment is short, which is convenient for subsequent management. Some programmes are as follows:

(1) streptomycin (or ethambutol), isoniazid, rifampicin and pyrazinamide were used in the intensive period of the first two months, 65438 0 times a day; After 4 months, continue to use isoniazid and rifampicin, once a day 1 time, and write 2s (e) hrz/4hr.

⑵ During the consolidation period, you can also take the medicine every other day (that is, three times a week) and write 2S (e) HRZ/4H3R3.

(3) You can also take medicine at intervals and write 2S3 (E3) H3R3Z3/4H3R3.

⑷ isoniazid, streptomycin, p-aminosalicylic acid (or ethambutol) were used in the intensive period, and two drugs were used in the consolidation period 10 month, and 2 HSP (e)/ 10HP (e) was written.

(5) Use isoniazid and streptomycin in the strengthening period of 1 month, and use them twice a week in the consolidation period of 1 1 month, written as 1HS/ 1H2S2.

Items (1), (2) and (3) above are shortened schemes, and items (4) and (5) are "conventional chemotherapy" schemes. If conditions permit, the shortening scheme should be adopted as far as possible.

If smear-negative cases are negative in culture, but X-rays and clinical manifestations suggest active pulmonary tuberculosis, they should be carefully excluded. Except for miliary pulmonary tuberculosis or patients with obvious cavities, the chemotherapy scheme for newly treated smear-positive cases can be adopted, and other newly treated smear-positive patients can adopt the following weaker schemes; 2SHRZ/2H2R2, 2H3R3Z3/2H3R3 or1sh/1HP (e), and the sputum bacteria were followed up.

2. The initial chemotherapy of retreatment cases is reasonable, tuberculosis has secondary drug resistance, sputum bacteria are positive, and the focus is prolonged repeatedly. The combination of sensitive drugs should be selected for retreatment cases. Drug sensitivity test of tuberculosis can help to choose drugs, but it usually takes a long time and is expensive. Therefore, the commonly used method in clinic is to choose drugs that have not been used or rarely used in the past, or drugs that have been used together regularly (maybe mycobacterium tuberculosis is still sensitive to them), and make another plan to combine two or more sensitive drugs for treatment.

For retreatment cases, the following schemes can usually be adopted:

(1) 2s (e) hrz/4hr, supervise chemotherapy to ensure regular medication. If the sputum bacteria do not turn negative at the end of the 6-month course of treatment, the consolidation period can be extended by 2 months. If long-term treatment does not turn negative, the following retreatment scheme can be adopted.

(2) The patients who failed the initial treatment rules can be treated with 2S3H3 R3 Z3E3/6HR3E3.

(3) Patients with chronic bacterial discharge can be treated with sensitive first-line drugs combined with second-line drugs, such as kanamycin (K), propylthioisoniazid (132 1Th) and capreomycin (CP). The course of treatment is 6- 12 months under the condition of closely observing the side effects. Fluoroquinolones (ofloxacin, ciprofloxacin, sparfloxacin, etc. ) has moderate anti-tuberculosis effect, and combined regimen can be used in the case of common drug resistance. When sputum bacteria turn negative, or serious side effects of drugs are unbearable, it is an indication to stop taking drugs.

(5) Evaluation index of curative effect, causes of failure and countermeasures.

1. Evaluation index Sputum bacteriology examination is the main index to evaluate curative effect. The sputum bacteria turned negative, indicating that the bacterial quantity in the focus was greatly reduced or extinct, and it was no longer the source of social infection. If it returns to normal, it means that the lesion has recurred and the treatment has failed. After a few days of reasonable chemotherapy, the amount of bacteria in sputum began to drop sharply, and the culture method could turn negative after 2 or 3 weeks. Sputum bacteria examination has high specificity and little interference from human factors; Lung X-ray examination is also an important basis for monitoring the prognosis of the disease. Combined with the results of sputum examination and clinical manifestations, the curative effect can be judged.

2. At the end of the course of chemotherapy failure, sputum bacteria failed to turn negative or turned positive during treatment. X-ray showed that the lesion failed to absorb, stabilize or worsen, indicating that chemotherapy failed. Most of the important reasons are unreasonable chemotherapy scheme, irregular drug use or premature withdrawal, or bacterial drug resistance and low immunity. In order to avoid failure, the chemotherapy plan must be made correctly, and patients should adhere to the early, appropriate, regular and full-course combined use of sensitive drugs under supervision. The new scheme should contain more than two kinds of sensitive drugs.

Second, symptomatic treatment.

(1) Toxic symptoms Most of the toxic symptoms of tuberculosis can subside within 65,438+0-2 weeks after effective anti-tuberculosis treatment without special treatment. For patients with severe tuberculosis poisoning symptoms such as caseous pneumonia, acute miliary tuberculosis, tuberculous meningitis with high fever, and pleurisy with massive pleural effusion, priority should be given to bed rest and anti-tuberculosis drug treatment. Sometimes the symptoms of poisoning are too serious, or the pleural effusion is not absorbed quickly. At the same time, effective anti-tuberculosis drugs and glucocorticoid (commonly used prednisone, 15-20mg/ day, taken orally for 3-4 times) can be used to reduce inflammation and allergic reaction, promote exudate absorption, and reduce the occurrence of fibrous tissue formation and pleural adhesion. After the toxic symptoms were relieved, the dosage of prednisone gradually decreased and the drug was stopped after 6-8 weeks. Glucocorticoid has no bacteriostatic effect, but it can inhibit the immunity of the body, and it can promote the spread of tuberculosis when used alone. This hormone has no effect on pleural thickening and chronic pleural effusion. Therefore, it must be applied on the basis of effective anti-tuberculosis drug treatment.

(2) Patients with hemoptysis can often stop a small amount of hemoptysis by resting quietly and eliminating nervousness. Use a small amount of sedatives and cough suppressants when necessary. The elderly, the infirm and those with pulmonary insufficiency should use strong antitussive drugs with caution when hemoptysis, so as not to inhibit cough reflex and respiratory center, so that blood clots cannot be coughed up and suffocation occurs. Other causes of hemoptysis should be excluded, such as secondary valve stenosis, disorder of coagulation mechanism, pulmonary infarction, infection, foreign body and autoimmune diseases.

There is a lot of hemoptysis. Take the affected side and gently cough up the accumulated blood in the trachea. Adding 5 units of pituitrin to 40 ml of 50% glucose is effective by slow intravenous injection. Or 10 unit can be added into 500 ml of 5% glucose solution for intravenous drip. Pituitrin can contract arterioles, including coronary arteries and capillaries of the heart, and reduce pulmonary blood flow, thus reducing hemoptysis. This medicine can also cause contraction of uterine and intestinal smooth muscle, so it is forbidden for patients with hypertension, coronary heart disease and pregnant women. Too fast injection can cause nausea, defecation, palpitation, pallor and other adverse reactions.

If there is too much hemoptysis, a small amount of blood transfusion should be given according to the measurement of hemoglobin and blood pressure. If a large amount of hemoptysis persists, the bleeding site can be determined by fiberoptic bronchoscopy, and then the bleeding site can be compressed or the diluted adrenaline sponge can be stuffed to stop bleeding. Balloon compression of Fogarty catheter can be used to stop bleeding. Cold saline can also be used for lavage. Or local application of thrombin or balloon compression to control bleeding. After bronchial arteriography found the bleeding focus, absorbable gelatin sponge was injected into the diseased blood vessels for embolization. Repeated massive hemoptysis is ineffective with the above methods, and there is no active lesion in the contralateral lung. The lung function reserve is still good and there is no contraindication. Lobectomy and segmental resection can be considered when the bleeding site is clear.

Special attention should be paid to keeping the respiratory tract unobstructed when rescuing massive hemoptysis. If there are signs of suffocation, you should immediately take a position with your head down and your feet high, pat your back to discharge blood clots, and dig out or suck blood clots in your mouth, throat and nose as soon as possible. If necessary, tracheal intubation or tracheotomy should be performed to relieve airway obstruction.

Third, surgical treatment.

In recent years, surgery has been rarely used for the treatment of tuberculosis. It is difficult to distinguish tuberculoma larger than 3cm from lung cancer. Lobectomy or pneumonectomy can be performed when unilateral fibrous thick-walled cavity after retreatment, long-term medical treatment fails to turn negative sputum, or unilateral damaged lung with bronchiectasis, functional loss and repeated hemoptysis or secondary infection. When the medical treatment of tuberculous empyema and/or bronchopleural fistula is ineffective and accompanied by ipsilateral active pulmonary tuberculosis, lobectomy-pleurectomy should be performed. Contraindications for surgical treatment are: active tuberculosis of bronchial mucosa, which is not within the scope of resection; The general condition is poor or the heart, lung, liver and renal insufficiency are obvious.

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