Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis, can invade many organs, the formation of pulmonary involvement tuberculosis (pulrnonary tuberculosis) is the most common. Row of bacteria important source of infection for the patient. The human body is not necessarily infected with TB disease, when the resistance is reduced or increased cell-mediated allergy, it may cause clinical disease. The basic pathological features of the disease exudative, cheese necrosis and other proliferative tissue reaction, formation of voids. Apart from a few acute onset gather outside, mostly chronic clinical course. It manifested as fever, weight loss, fatigue and other symptoms of cough, hemoptysis and other respiratory manifestations. If timely diagnosis, and to the proper treatment, most of the available clinical recovery. Since the 1950s, the trend of tuberculosis has decreased, but the regional epidemic control is still uneven, it is still currently a prominent public health issue, is one of the top ten causes of death in the country.
Antituberculosis chemotherapy for TB control play a decisive role, reasonable intralesional chemotherapy can destroy the bacteria, ultimately recovered. Rest and nutrition therapy only play a supporting role.
First, the anti-TB chemotherapy (referred to chemotherapy)
(A) Principles of chemotherapy
The main effects of chemotherapy is to shorten the infectious period and reduce mortality, morbidity and infection. For each particular patient, for the main measures to achieve clinical and biological cure, chemotherapy is a reasonable means of active tuberculosis insisted early in conjunction with, adequate, regular and full use of the principles of sensitive drugs. Mainly refers to the so-called Early early treatment of patients, if it is found immediately after diagnosis and drug treatment; joint action is defined according to the characteristics of the disease and anti-TB drugs, combined with two or more drugs to enhance and ensure the efficacy; refers to an appropriate amount depending on the condition and provide for different dosage of different individuals; the law even if the patient must strictly follow the prescribed method of administration of chemotherapy, to adhere to a regular treatment, can not arbitrarily change the program or undue free withdrawal is also not free to intermittent medication; patients must follow the full program Naizhi adhere to the rule set by the full course of treatment, short-course chemotherapy is usually 6 to 9 months. Generally, untreated patients with standard treatment in accordance with the above principles, the efficacy of up to 98%, the recurrence rate of less than 2%.
Active TB are indications of chemotherapy. Induration of long lesions they do not need chemotherapy. As part of the induration, sputum negative, could observe a stage, if X-rays show no active lesions, sputum is still negative, no obvious toxic symptoms of tuberculosis, also do not need chemotherapy.
1, early, in conjunction with, adequate, regular and full medication active lesions in exudative stage, or cheese-like necrosis and even the formation of hollow, mainly Mycobacterium tuberculosis bacteria in Group A lesion growth metabolism, anti-TB drugs are often You can maximize the bactericidal or bacteriostatic effect. Local lesions rich blood supply, drug concentrations would also be conducted to help promote inflammation absorption components, reduced or closed cavity, sputum negative. Therefore, early active lesions reasonable chemotherapy, results were satisfactory.
Experiments show that lung lesions cheese per 1g tissue or cavity, about 106 to 1010 TB. Never had contact with TB TB drugs, sensitivity to drugs are not identical. About every 105 to 106 TB bacteria may have a genetic mutation because isoniazid or streptomycin resistance. Meanwhile the two drugs are resistant TB by about 1011, only one, but three kinds of bacteria resistant to drugs is less. As can be seen in a single-drug therapy, although can be nipped in the portion susceptible, but may leave a small number of resistant bacteria continue to multiply, eventually grow resistant advantages. Such as joint use of two or more drugs, reduce drug-resistant, the effect is better than single drugs.
The dose should be appropriate, inadequate dosage, the drug within the organization in order to achieve an effective concentration letter, and easy to produce bacterial secondary resistance. Excessive drug is easy to produce adverse reactions. TB slow growth, sometimes only occasionally breeding (B, C bacteria), and should therefore be the drug in the body long-term effective concentration. Regularly throughout treatment, but early withdrawal is the key to successful chemotherapy.
2, can play a bactericidal effect of TB drugs and blood (including macrophages) drug concentration in normal doses, to achieve the above in vitro minimum inhibitory concentration (MIC) of 10 times, otherwise the only antimicrobial effect. Conventional dosage isoniazid and rifampicin inside and outside the cell can reach that level, said the whole fungicides. Pyrazinamide and streptomycin are also fungicides, but streptomycin to play the biggest role in the slightly alkaline environment, and rarely penetrate phagocytic cells, intracellular TB invalid. Although pyrazinamide can penetrate phagocytic cells, but only have a bactericidal effect in acidic environments, so both are only half as fungicides. Ethambutol, sodium aminosalicylate, etc. are bacteriostatic agents, when conventional doses of the drug concentration can not be more than 10 times the MIC, increase the dose is prone to adverse reactions.
TB mostly in the early lesion within the extracellular, then isoniazid bactericidal effect is the strongest, followed by streptomycin. Inflammation of the tissue local pH decrease, slowing bacterial metabolism (C flora), together with some of phagocytic cells in the TB (B flora), are sensitive to rifampin and pyrazinamide. Such residual bacteria killing (B flora), helps to reduce future recurrence.
(B) chemotherapy
1, the "standard" chemotherapy and conventional short-course chemotherapy in the past 12 to 18 months using the therapy, known as the "standard" chemotherapy, but the long duration, many patients can not be completed, the effect is limited. Since the advent of rifampicin, and in combination with other drugs, found that 6 to 9 months of therapy (DOTS) with standard chemotherapy has the same effect, it is now widely used short-course chemotherapy, the program requested must comprise two bactericidal drugs, iso isoniazid and rifampicin, a strong bactericidal (bacteria of A) and sterilization (for B, C bacteria) effect.
2 ,. intermittent treatment, two-stage drug experiments showed that after a few hours in contact with TB drugs, often retard the growth of the number of days. Therefore, regular medication three times a week (intermittent treatment), can achieve the same effect with the drug every day. Within 1 to 3 months to start chemotherapy, daily dosing (strengthening stage), three times a week after intermittent treatment (consolidation phase), the effect of daily medication is basically the same, facilitate the monitoring of medication to ensure complete a full course of chemotherapy. When using intermittent therapy medication three times a week, should the combination, each of isoniazid, rifampicin, ethambutol dose may be appropriate to increase; however streptomycin, p-amino salicylic acid, sodium acetate, sulfur isonicotinoyl amine more adverse reactions, each dose should not be increased (table 1).
Table dose commonly used anti-TB drugs for adults and major adverse effects
Drug name abbreviations daily dose (g) intermittent treatment 1, (g) bacteriostatic mechanism of adverse reactions
Isoniazid H, INH0.30.6 ~ 0.8DNA peripheral neuritis synthesis, sometimes liver damage
Rifampicin R, RFP0.45 ~ 0.6 * 0.6 ~ 0.9mRNA synthetic liver damage, allergic reactions
Streptomycin S, SM0.75 ~ 1.0 △ 0.75 ~ 1.0 protein synthesis hearing loss, dizziness, impaired renal function
Pyrazinamide Z, PZA1.5 ~ 2.02 ~ 3 pyrazine acid inhibitory gastrointestinal discomfort, liver dysfunction, hyperuricemia, joint pain
Ethambutol E, EMB0.75 ~ 1.0 ** 1.5 ~ 2.0RNA synthetic optic neuritis
Amino salicylic acid sodium P, PAS8 ~ 12 *** 10 ~ 12 intermediary metabolism gastrointestinal discomfort, allergic reactions, liver damage
Propylthiouracil isonicotinoyl amines 1321Th0.5 ~ 0.750.5 ~ 1.0 protein synthesis gastrointestinal discomfort, liver damage
Kanamycin K, KM0.75 ~ 1.0 △ 0.75 ~ 1.0 protein synthesis hearing loss, dizziness, impaired renal function
Capreomycin Cp, CPM0.75 ~ 1.0 △ 0.75 ~ 1.0 protein synthesis hearing loss, dizziness, impaired renal function
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3, anti-tuberculosis drug supervision administration at least six months, even take up to a year and a half, patients often difficult to adhere to. Urge timely medical treatment, strengthening visits, obtain the patient cooperation is particularly necessary. Strengthening stage once-daily administration, the peak plasma concentration can be formed, compared with daily fractionated treatment efficacy is preferred, and the convenience of patients, improve patient adherence to medication and complete the full rate.
(Iii) anti-TB drugs
Ideal anti-TB drugs sterilization, sterilization or strong antimicrobial effect, low toxicity and reduce adverse reactions, adequate inexpensive, easy to use, drug source; orally or injected drugs can achieve an effective concentration in the blood, and It can penetrate phagocytic cells, or cerebrospinal fluid within the peritoneal cavity, rapid and lasting effect.
1, isoniazid (isoniazid, H) has a strong bactericidal, it can be administered orally, fewer adverse reactions, low cost and other advantages. Its main function is to inhibit M. tuberculosis deoxyribonucleic acid (DNA) synthesis and hinder bacterial cell wall synthesis. After oral administration, rapid absorption, tissue infiltration, through blood-brain barrier, killing intracellular metabolism of active TB or stationary. Pleural effusion, cheese-like lesions and drug concentrations in cerebrospinal fluid are also quite high. The usual dose for adults daily 300mg (or daily 4 ~ 8mg / kg), an oral; children daily 5-10mg / kg (not to exceed daily 300mg). Tuberculous meningitis and acute tuberculosis millet dose may be increased (there may be complicated by peripheral neuritis, can prevent 300mg of vitamin B6 daily while increasing the dose; but large doses of vitamin B6 can affect the efficacy of isoniazid, so use when general dose of isoniazid, no need to add vitamin B6), until the acute toxicity symptoms recoverable conventional dose. Isoniazid in vivo inactivated by acetylation, acetylated individual differences in speed are often lower rapid acetylation blood concentration, there shall be considered to increase the dose intermittent administration.
Conventional dose of the drug adverse reactions occur rarely, occasionally peripheral neuritis, central nervous system toxicity (excitatory or inhibitory), liver damage (serum alanine aminotransferase) and the like. 3 months of isoniazid alone, sputum resistance rate up to 70%.
2, rifampicin (rifampin, R) is a semi-synthetic derivative of rifamycin, a broad-spectrum antibiotic. Its mechanism is to kill TB bacteria inhibiting RNA polymerase, hinder its mRNA synthesis. Intracellular rifampicin, a strong external metabolism and reproduction occasionally TB (A, B, C bacteria) have a role, often in combination with isoniazid. Adult 1 day, fasting oral administration of 450 ~ 600mg. The drug adverse reactions are mild, in addition to gastrointestinal discomfort, flu syndrome, the occasional transient hepatic dysfunction. Long rifamycin derivatives such as rifapentine (rifapentine, DL473) long half-life in humans, orally once a week, with daily rifampin similar effect. Rifamycin spiral piperidine (ansamycin, LM427, rifabutin) have some effect on other anti-TB drug failure strain (eg bird complex mycobacteria) than rifampin strong.
3, streptomycin (streptomycin, S) is a broad spectrum aminoglycoside antibiotic, has bactericidal action against TB, TB can interfere with the activity, impede protein synthesis. TB less effect on the cell. Dosage: Adult daily intramuscular injection 1g (50 years of age or renal dysfunction available 0.5 ~ 0.75g). Intermittent therapy twice a week, every muscle injection 1g. Pregnant women with caution.
The main side effects of streptomycin for the eighth cranial nerve damage, manifested as dizziness, tinnitus, deafness, severe cases should be promptly discontinued, severe renal impairment should not be used. Other allergic rash, exfoliative dermatitis, drug fever, etc., anaphylactic shock is rare. Monotherapy is easy to produce drug resistance. Other aminoglycoside antibiotics, such as kanamycin, capreomycin, purple neomycin although also anti-TB effect, but the effect is not and streptomycin, similar adverse reactions.
4, pyrazinamide (pyrazinamide, Z) can kill within phagocytes, acidic environment of TB. Dose: daily 1.5g, 3 times orally, occasionally hyperuricemia, joint pain, gastrointestinal discomfort and liver damage and other adverse reactions.
5, ethambutol (ethambutol, E) of TB has antibacterial effects, when combined with other anti-TB drugs and may retard bacterial resistance to other drugs. Dosage: 25mg / kg, 1 times a day orally for 8 weeks to 15mg / kg, adverse reactions to their little advantage, occasional gastrointestinal discomfort. Overdose can play the ball after optic neuritis, vision loss, reduced vision, central blind spot, etc., can be restored more than once the withdrawal.
6, p-aminosalicylic within (sodium para-aminosalicylate.P) of antibacterial drugs with streptomycin, isoniazid, or in combination with other anti-TB drugs, can delay the onset of resistance to other drugs. The antibacterial effect may during the synthesis of folic acid with TB ammonia acid (PABA) competition, affect the metabolism of Mycobacterium tuberculosis. Dosage: Adult daily 8 ~ 12g, every 2 to 3 times a day orally. Adverse reactions are loss of appetite, nausea, vomiting and diarrhea. The drug after meals can reduce gastrointestinal reactions, can also add a daily 12g dark intravenous infusion in 5% to 10% glucose solution 500ml, and a month later still changed to oral.
(Iv) chemotherapy
Depending on the severity, with or without sputum and bacterial resistance, as well as the economic situation, drug supply source, the choice of chemotherapy. No matter which must comply with the aforementioned principles can only be effective chemotherapy.
1 newly diagnosed cases of anti-TB program without drug treatment, some sputum smear-positive TB (smear), severe illness, infectious; and some smear-negative, small lesions, the use of chemotherapy also have different strength.
Smear positive cases, regardless of whether the culture is positive, can be utilized to isoniazid (H), rifampicin (R) and pyrazinamide (Z) based on a combination of the six-month DOTS program. Soon sputum often negative, short course, to facilitate follow-up management.
(1) strengthen the first two months of streptomycin (or ethambutol), isoniazid, rifampin and pyrazinamide, 1 day; after four months continue with isoniazid and rifampicin flat, 1 day to 2S (E) HRZ / 4HR representation.
(2) may also be a period of consolidation in the drug every other day (ie medication three times a week) to 2S (E) HRZ / 4H3R3. (Lower right corner number is the number of drugs per week).
(3) can also be intermittent throughout the medication to 2S3 (E3) H3R3Z3 / 4H3R3 representation.
(4) to strengthen the use of isoniazid, streptomycin and sodium aminosalicylate (amine or an alcohol), a period of consolidation with two kinds of drugs for 10 months, to 2HSP (E) / 10HP (E) represented.
(5) strengthening of a month with isoniazid, streptomycin, consolidation of 11 months of treatment twice a week to 1HS / 11H2S2 representation.
Above (1), (2), (3) for the short term chemotherapy, (4), (5) the "standard protocol." If conditions permit, to make use of short-course chemotherapy program.
Smear Yin Pui Yin patient, except may be smear positive patients with significant new social program miliary tuberculosis or hole, using the following regimens: ①2SHRZ / 2H2R2; ②3H2R2Z2 / 2H2R2 (every other day throughout the application); ③1SH / 11HP (or E).
Of untreated patients, International Union Against Tuberculosis and Lung Disease Association recommended chemical solution is suitable for the national anti-TB (Table II), development of treatment programs available for reference.
Table II countries tuberculosis chemotherapy Tuberculosis Plan
Course of chemotherapy treatment regimens
6 months 2RHZ / 4RH8 months 2SRHZ / 6TH or 6EH
2ERHZ / 4RH or 4R2H22SRHZ / 6S2H2Z2
2SRHZ / 4RH or 4R2H2
2, retreatment regimen as the first treatment of chemotherapy unreasonable, TB produce secondary resistance, sputum remains positive, persistent recurrent disease. Retreatment cases should choose joint sensitive drugs. Drug sensitivity test helps select the medication, but time-consuming longer, larger expenses. Clinically patients according to previous drug use, select an unused past few used or has joint rules used drugs (which may still be susceptible to the bacteria), and the other set programs, joint two kinds or two kinds more sensitive drugs.
Retreatment cases, generally available the following scenario:
(1) 2S (E) HRZ / 4HR, supervise chemotherapy administration to ensure laws. At the end of six months of treatment, if still negative sputum, consolidation period may be extended for two months. As prolonged treatment is still sputum remains positive, retreatment may be following the program.
(2) newly diagnosed patients failed rule, available 2S3H3Z3E3 / 6H3R3E3.
(3) chronic row of bacteria sensitive to first-line drugs were available and combined with second-line drugs, such as kanamycin toxin (K), propylthiouracil isonicotinoyl amine (1321Th), capreomycin (Cp), should be closely observed adverse drug reactions, medication 6 to 12 months is appropriate. Fluoroquinolones have antituberculosis moderate effect on the cases commonly used drugs has generated resistance, may be added in combination with the program. If bacteria overcast fistula, or serious adverse reactions, indications are discontinued.
(V) determine the condition and efficacy assessment, treatment failure
1, according to the extent of disease and therapeutic evaluation of activities can be divided into the aforementioned known disease progression, and improved absorption of the stable. General improvement of absorption and stability of the condition improved, advanced for the worse. Its judgment should be based on clinical symptoms, X-ray showing the row of bacteria and comprehensive analysis of the situation.
(1) Clinical symptoms: observe whether the afternoon fever, night sweats, loss of appetite, general shortage, weight loss and other TB symptoms worsen and procedural changes. Such symptoms were relieved or disappeared prompted condition improved; or if symptoms significantly changed from a light weight indicates deterioration. In addition, cough, sputum, hemoptysis and other changes in respiratory symptoms may be used as a reference.
(2) X-ray examination: the condition is judged indispensable indicators, is also an important basis for monitoring of the disease outcome of patients with no obvious clinical symptoms mainly rely on X-ray, X-ray can determine the lesion location, extent, nature , but also to control observation of dynamic change. Cottony clouds infiltrates absorb, dissipate, narrow; or converted to higher density, clear boundary of proliferative diseases such as fibrosis, calcification; original narrow cavity, said Deng Jun closed condition improved or cured. Conversely, the proliferative lesions into exudative lesions or invasive lesions expand, bronchial disseminated or acute, subacute hematogenous, caseous necrotic lesions, cavitation, etc. are deteriorated performance.
(3) sputum: tuberculosis in the sputum bacteria row or not is an important indicator to determine the condition assessment procedures and efficacy. Sputum examination and high specificity less affected by human factors. If sputum remains positive, compared with open tuberculosis, suggesting a high degree of disease activity, and for the social source of infection of tuberculosis, pose a threat to the surrounding population. After treatment repeatedly checked and found negative for TB or less, which is indicative of better; such as monthly sputum examination at least once, months were negative, it means that into the stable. Then, if the row of bacteria appear again for disease worsening performance. ESR acceleration prompted active disease worsening; but not have active tuberculosis ESR growth, lesions improved and stable patients were nearly normal erythrocyte sedimentation rate.
2, the end of the course of treatment failure sputum negative conversion failed, or in transit positive effect, X-ray showed lesions not absorbed, stable, and further deterioration, both indicate treatment failure, a so-called refractory pulmonary tuberculosis. Study its causes, in addition to drug-resistant TB infection, medication is not standardized, intermittent medication or monotherapy, but still with some patients chemotherapy drug allergies, chemotherapy drugs can not be used because of serious adverse reactions or chemotherapy drugs is difficult to adhere to treatment, the body immunocompromised (HIV infection), poor physical and other factors.
Drug-resistant tuberculosis (DR-TB) especially multidrug-resistant tuberculosis (MDR-TB) epidemic seriously, we are making anti-TB treatment is facing new challenges. 1994, WHO and the International Union Against Tuberculosis Lung Disease began anti-TB drug resistance monitoring of global planning, which lasted 3 years of work showed that, in 35 countries on five continents monitoring delegates found 20 percent of the world's population of double-resistant HR MDR-TB accounted for 2% to 14%, most of them belonging monotherapy, irregular, secondary multidrug resistance unreasonable treatment of joint programs human factors caused. In countries with weak TB control, primary multi-drug resistance was also found an upward trend. Once the occurrence of drug-resistant tuberculosis, chemotherapy drugs they use expensive price, poor efficacy, serious adverse events, treatment costs may be 100 times the new smear positive pulmonary tuberculosis patients. Adhere to the rational use of chemotherapy, and adopt comprehensive prevention and control measures, improve immune function and help prevent the occurrence of drug-resistant TB.
In order to effectively prevent treatment failure, chemotherapy must be properly formulated, patients should insist on an early, regular, regular, full combined with sensitive drugs under the supervision of. Only in the case of resistance has serious adverse reactions or indeed confirmed that the bacteria has been generated, it changed to a new chemotherapy. The new program should include two or more sensitive drugs.
Second, symptomatic treatment
(A) toxic symptoms
Toxic symptoms of tuberculosis and more effective anti-TB treatment can disappear in 1 to week, usually you do not have special treatment. Severe toxic symptoms of tuberculosis caseous pneumonia, acute miliary tuberculosis, tuberculous meningitis, high fever, etc., or a large number of tuberculous pleurisy with pleural effusion, should be bed rest and the use of anti-TB drugs as soon as possible. Also in the use of effective anti-TB drugs at the same time, the addition of corticosteroids (commonly prednisone daily 15 ~ 20mg, three to oral) to reduce inflammation and allergic reactions, and promote absorption of exudate, reducing fibrous tissue formation and pleural adhesions. Toxicity symptoms to be severe, prednisone dose decreasing to 6 to 8 weeks withdrawal. Glucocorticoids pleural thickening and has no role in the formation of adhesions. Therefore, it should be used with caution in effective anti-TB treatment basis.
(B) hemoptysis
If only a small amount of bloody sputum or hemoptysis, symptomatic treatment, including rest, cough, sedation, commonly used drugs Pentoxyverine soil root powder, codeine, carbazochrome (security network of blood) and the like. Old and feeble, pulmonary insufficiency, caution strong antitussive, so as to avoid inhibiting reverse cough and respiratory center, so that can not be discharged blood clots caused by suffocation. To exclude other reasons hemoptysis, such as mitral stenosis, pulmonary infection, pulmonary infarction, coagulation disorders, autoimmune diseases.
Moderate or heavy hemoptysis should be strict bed rest, ice packs placed chest and alternate with blood. Lateral position, will remain in the blood gently intratracheal cough. Vasopressin 10U applied to 20 ~ 30ml saline or glucose solution, the slow intravenous infusion (15 to 20 minutes), then 10 ~ 40U in 500ml of 5% glucose solution intravenous maintenance therapy. Posterior pituitary is known as contraction of small arteries, including the coronary artery and capillary action to reduce pulmonary blood flow, thereby reducing hemoptysis. The drug can still smooth muscle contraction of the uterus and therefore avoid for pregnant women and patients with hypertension, coronary atherosclerotic heart disease. Injection too fast can cause nausea, it is intended, palpitations, pale and other adverse reactions.
If excessive hemoptysis, blood transfusion may be appropriate discretion. Than those who hemoptysis, bleeding sites can be found by bronchoscopy, noradrenaline 2 ~ 4mg + 4 ℃ saline 10 ~ 20ml topical instillation. Or placed Fogarty balloon catheter (outer diameter 1mm, inflatable 0.5 ~ 5.0ml) with bronchoscopy clogging the bleeding site to stop bleeding. In addition to still use Kinoshita method with thrombin or fibrinogen bronchoscopy lavage hemostasis, should be fully prepared to make the necessary rescue. Repeated hemoptysis by the above method is invalid, no activity contralateral lung disease, pulmonary function reserve acceptable nor obvious contraindications, consider lobectomy, segmentectomy in clear bleeding site conditions.
Hemoptysis suffocation is the leading cause of hemoptysis necrosis, need to guard against, and actively preparing for the rescue before hemoptysis asphyxia symptoms include chest tightness, gas hold back, a lip cyanosis, pallor, cold sweat dripping, irritability. Rescue measures should be particularly injection keep the airway open, take Trendelenburg prone position high of 45 °, pat the back, the rapid discharge of blood, and dig or suction outlet as soon as possible, pharynx, larynx, nasal blood clots. Rigid bronchoscopy is necessary to attract, endotracheal intubation or tracheotomy to relieve airway obstruction.
Third, the surgical treatment
Surgery has been less used in the treatment of tuberculosis. Of greater than 3cm of tuberculosis and lung cancer is difficult to identify the ball, one-sided hollow fiber retreatment thick, long-term medical treatment failed to sputum conversion by, or unilateral destroyed lung with bronchiectasis, has lost function and have repeatedly hemoptysis or secondary infection, can be used for lung or pneumonectomy. Tuberculous empyema and (or) bronchial fistula after medical therapy and ipsilateral active TB, it is desirable for the lung - pleural resection. Surgical treatment contraindications are: bronchial mucosa with active tuberculosis, but not removed within the scope of those poor general condition or have significant heart, lung, liver and kidney dysfunction.
