There is a marked increase in the incidence of tuberculosis globally, and the incidence of spinal tuberculosis, which is a common secondary tuberculosis, has also increased significantly. The treatment of tuberculosis focuses on drug therapy, as does the cure of spinal tuberculosis. Without anti-tuberculosis drug therapy, the effectiveness of surgery cannot be guaranteed. (a) Anti-tuberculosis drugs The concentration of drugs in the blood and cells can only play a bactericidal role when it reaches more than 10 times of the minimum inhibitory concentration (MIC) in the test tube under the conventional dosage of Zhang Qiang, Department of Orthopaedic Surgery, Shandong Provincial Thoracic Hospital, or else it can only play a bacteriostatic role. Isoniazid and rifampicin are able to meet this requirement both inside and outside the cell, which is called a total bactericide, streptomycin and pyrazinamide are also bactericides, but can only be regarded as half a bactericide, because streptomycin can play a maximum role in a biased alkaline environment and is ineffective against intracellular bacteria, whereas pyrazinamide can be permeated into phagocytosis cells, and can play a maximum role in a biased acidic environment. Ethambutol, p-aminosalicylic acid and aminothiourea are bacteriostatic agents. The bacteriostatic mechanisms and major adverse effects of commonly used antituberculosis drugs are shown in Table 1, and the dosages of major antituberculosis drugs are shown in Table 2 [1]. Table 1 Bacteriostatic mechanism and major adverse reactions of commonly used antituberculosis drugs Drug Abbreviation Bacteriostatic mechanism of action Major adverse reactions Isoniazid Rifampicin Streptomycin Pyrazinamide Ethambutol Para-aminosalicylic acid Ammonia thiourea Kanamycin Criminomycin Prothioisonicotinic acid hydrazide H, INH R, RFP S, SM Z, PZA E, EMB P, PAS T, Tb1 K, KM Cp, CPM 1321Th DNA Hearing loss, vertigo, renal impairment Hearing loss, vertigo, renal impairment Gastrointestinal distress, hepatic impairment Table 2 Dosage of major antituberculosis drugs Drug name Adult daily dose (g) Child daily dose (mg/kg) Intermittent daily dose (g) Isoniazid 0.3-0.4 (5-8mg/kg) 10-15 0.6-0.8 Rifampicin 0.45-0.60 (8-10mg/kg) 10-20 0.45-0.60 (8-10mg/kg) 10-20 0.6-0.9 Rifapentine 0.45biw0.6qw Pyrazinamide 1.5-2.0 (20-30mg/kg) 20-30 2.5 Ethambutol 0.75-1.0 (15mg/kg) 1.5 Streptomycin 0.75-1.0 (15-20mg/kg) 15-30 0.75-1.0 Isethionamide propylthio Nicotinamide 0.5-0.75 10-15 0.5-1.0 Crimithromycin 0.75-1.0 0.75-1.0 Kanamycin 0.75-1.0 0.75-1.0 (II) Formulation and selection of chemotherapeutic regimen[1-5] According to the condition and onset of disease of the tuberculosis patients, the comprehensive analysis is made to determine the initial treatment, recurrent treatment, relapse, and drug-resistant cases, and the corresponding tuberculosis drug treatment regimen is given. According to the condition and morbidity of TB patients, we should adhere to the principle of “early, combined, appropriate amount, regular and full use of sensitive drugs”, and at least 2-3 kinds of bacteriostatic drugs (H/R/S/Z) at the same time, and the duration of treatment should be increased or decreased according to the condition of the patients; for the patients who are combined with other diseases (liver and kidney dysfunction, diabetes mellitus, poor hematopoietic function, or immune diseases, etc.), we should use them with caution, or we should choose the drugs with low toxicity and low amount. For other diseases (liver and kidney function damage, diabetes, hematopoietic function or immune disease, etc.), use cautiously or use low toxicity anti-tuberculosis drugs, and increase the time of drug treatment. 1. Commonly used regimen The best chemotherapy regimen should meet the following conditions: (1) the best combination of drugs: it should be composed of bactericidal drugs, sterilizing drugs and drugs to prevent the development of drug resistance; (2) it must be in accordance with the prescribed types of drugs, dosage, number of times of administration and sufficient duration of treatment; (3) it should have high therapeutic efficacy and low toxicity, and it is easy to be accepted by the patients and be widely practiced. (1) Long course chemotherapy (standard chemotherapy) INH+PAS, with the addition of SM in the first 3 months, the full course of treatment is 1.5 years.In the 1950s, the British Medical Research Council (BMRC) summarized the efficacy of the standard chemotherapy for spinal tuberculosis in a number of articles, with a cure rate of 89%, a relapse rate of 3%, and a mortality rate of 1.4%. The efficacy of this chemotherapy program is affirmed by scholars at home and abroad. (2) Short-course chemotherapy program Principle: Chemotherapy should use highly effective, sensitive, low-toxicity and economical drugs. The program should include at least 2-3 bactericidal drugs, isoniazid and rifampicin are the most basic drugs, indispensable, plus pyrazinamide and other drugs used in combination, for A, B, C3 bacterial group sterilization to prevent recurrence, constituting the standard short-course chemotherapy program, and all the drugs are taken once in the morning before the meal is preferred. In recent years, there are more short-course chemotherapy regimens for spinal tuberculosis, as shown in Table 3. Table 3 Commonly used short-course chemotherapy regimens for spinal tuberculosis Chemotherapy regimen Surgery Observation (months) Relapse rate Author 6RH (SMqd for the first two months) 6EH (SMqd for the first two months) 6RH 6RH 9RH 6RH+S/2/week 9RH+S/2/week 4SHRE/5HRE 4SHRE/5H3R3E3 There are three main types of drugs: TNF, RFP, and PZA. the combination of the three drugs can bring out their respective and synergistic effects. For example, INH has the strongest bactericidal effect on bacteria with strong metabolism, RFP is the most effective for intermittent metabolism bacteria; PZA plays a special role for intracellular bacteria in acidic environment. And INH and RFP are the best combination for preventing drug resistance, which can greatly shorten the course of treatment. (3) Ultra-short course chemotherapy regimen The chemotherapy regimen is 2SHRZ/2.5H2R2Z2, which is recommended by the National Collaborative Group of Short Course Chemotherapy for Tuberculosis. The intensive period is 2 months, followed by a consolidation period of 4.5 months. In the chemotherapy of tuberculosis, any chemotherapy regimen less than six months is ultra-short-course chemotherapy regimen, which has been recognized internationally and has better effect in the chemotherapy of tuberculosis. According to the theoretical basis of ultra-short-course chemotherapy and clinical research, it is inferred that ultra-short-course chemotherapy is not only feasible in spinal tuberculosis, but also should have better curative effect than pulmonary tuberculosis. (1) The treatment of spinal tuberculosis is more additional to surgical treatment than pulmonary tuberculosis. Surgical treatment removes the tuberculosis foci, and drugs are more likely to control the lesions. (2) Spinal tuberculosis is a type of extrapulmonary tuberculosis, and prospective controlled studies have shown that the results of short-course chemotherapy for almost all extrapulmonary tuberculosis are similar to those for pulmonary tuberculosis. (3) A short course of chemotherapy for 6 months has produced favorable results in the treatment of spinal tuberculosis. (4) 4.5-5.5 months of ultra-short-course chemotherapy is feasible in pulmonary tuberculosis, so it should be feasible in spinal tuberculosis. Domestic scholars have conducted relevant studies on this, and the results show that its therapeutic effect is not different from that of standard treatment and short-course chemotherapy, but it still needs large samples for long-term follow-up observation. For example: 4SHRE/5H3R3E3 program in the drug code before the 4 and 5 represents the duration of 4 months and 5 months, the code H3 indicates that isoniazid is given intermittently 3 times a week, and the rest of the analogous, before the slash in the program is the intensive phase, after the slash is the consolidation phase, the full duration of this program is 9 months. t stands for rifapentine. 2. Selection of chemotherapy regimen (1) Treatment of primary spinal tuberculosis Primary spinal tuberculosis refers to: (1) patients who have not yet begun anti-tuberculosis treatment; (2) patients who have not completed the full course of standard chemotherapy regimen; (3) patients who have been on irregular chemotherapy for less than 3 months. For the treatment of primary spinal tuberculosis WHO recommends the use of standard chemotherapy program, patients with mild symptoms can be deleted in the intensive period of streptomycin, for the effect of slow patients can increase the consolidation of the drug time. In recent years, short-course chemotherapy program is used in the treatment of primary treatment of spinal tuberculosis, and adjust the treatment program according to the treatment effect, that is, the unfixed short-course chemotherapy program, after the intensive period, according to the condition of the consolidation period will be extended appropriately, for example, the 4SHRE/5HRE program is changed to 4SHRE/XHRE, and the X indicates the extended month. (2) Treatment of relapsed spinal tuberculosisRelapsed spinal tuberculosis refers to (1) patients who failed conservative treatment; (2) patients with localized lesion recurrence after surgery; (3) patients with irregular chemotherapy for more than 3 months. The program of retreatment: intensive period of 5-6 months/consolidation period of 7-12 months, chemotherapy regimen H/R(T)/E/Z(TH)/S(KM)/O is the main drugs, and adjusted several times according to the therapeutic effect and the results of drug sensitivity test. (3) Treatment of drug-resistant spinal tuberculosis[6,7] The chemotherapeutic regimen for drug-resistant and multidrug-resistant spinal tuberculosis advocates the use of drugs based on the results of drug sensitization, and the course of treatment can be extended to 24 months, and WHO recommends that the first-line and the second-line antituberculosis drugs can be used in combination. First-line drugs can still be selected according to the drug sensitivity; ① SM in the intensive phase can be used for 3-5 months, the elderly and due to the inconvenience of injections commonly used EMB alternative, but due to the reduction of its application, now SM-resistant cases than INH/RFP reduced. ② PZA is mostly used in the intensive phase of standard short-course chemotherapy, so the frequency of possible resistance to this drug is low, and it is often used now. (iii) EMB: antimicrobial effect is similar to SM and is also the first choice of commonly used drugs. Second-line antituberculosis drugs are mostly the main drugs in the treatment of drug-resistant spinal tuberculosis. Sodium para-aminosalicylate is a bacteriostatic agent and is used to prevent resistance to other drugs. INH-resistant strains are partially sensitive to isoniazid p-aminosalicylate. The regimen for which no drug sensitivity results were obtained: 3TH,S(KM/AM)ZO/18THO; H/R-resistant: 3-6THOEZAK(SM/AM)/18THOE; H,R,S,E-resistant: 3-6THOZKM(AK)/18THOCS. In our opinion, although domestic and foreign experts have tried to adopt the “short-course We believe that although experts at home and abroad have tried to use “short-course” or even “ultra-short-course” chemotherapy to replace the traditional standard anti-tuberculosis treatment program, and have made some achievements. However, with the increase in the number of drug-resistant TB strains, the short-course and ultra-short-course regimens have been challenged, and in the current situation where the monitoring of drug-resistant cases is not yet widespread, especially the use of single drugs and unstandardized combinations of drugs, insufficient courses of drugs, or localized use of drugs, etc., not only affects the effectiveness of the treatment, but also may be one of the reasons for the emergence of drug-resistant strains. We should pay more attention to the application of standard chemotherapy program and adjust the types, doses, routes and methods of anti-tuberculosis drugs according to the therapeutic effect, toxic side effects of anti-tuberculosis drugs and drug sensitivity test results. (C) Problems noted in chemotherapy treatment 1. Anti-tuberculosis drug toxic side effects and treatment[8] can be categorized into anaphylactic reaction and drug toxicity reaction. (1) The frequency of anaphylactic reactions accounts for the first place of side effects (about 60%), and the majority of serious side effects are caused by rifamycin, which occurs mostly within 1-2 months after taking the drug. Multiple drug allergy, regardless of the severity of the reaction, to quickly stop the drug, early desensitization as the principle, after determining the allergen, to use the usual amount of 1/10 or less for desensitization, and to develop emergency treatment measures, severe allergy should not be repeated verification. Anaphylactic shock is resuscitated according to shock. Almost all anti-tuberculosis drugs can cause skin rashes, commonly caused by INH, SM, PAS, etc. Scarlet fever-like, eczema-like and purpura-like rashes, and severe cases can cause exfoliative dermatitis. It should be treated symptomatically with anti-allergic and antipruritic drugs. (2) SM, KM, CP have certain toxicity to hearing and vestibule, and should not be used in elderly patients with renal impairment and hearing impairment; Tb1 causes leukopenia and hemolytic anemia, PZA can cause joint pain, EMB can cause visual impairment, OFLX affects bones, and is contraindicated for developing children; drug-related liver injury is the most common serious adverse reaction in the course of anti-tuberculosis treatment, especially in the case of drugs containing rifampicin, isoniazid, isoniazid and other drugs. Drug induced liver injury is the most common serious adverse reaction during antituberculosis treatment, especially in the regimen containing rifampicin, isoniazid and pyrazinamide. In order to reduce the damage of anti-tuberculosis drugs to liver function and ensure the success of chemotherapy program, we believe that: ① before the start of chemotherapy, we must ask the medical history carefully, and patients with hepatitis B virus, alcoholism and schistosomiasis are prone to cause liver function damage. Before chemotherapy, it is best to include liver function and HBVM in the routine examination before tuberculosis chemotherapy. ② chemotherapy ALT increased but not more than 200U should continue chemotherapy under close observation, such as ALT increased or decreased, while AST increased more than three times the normal value should be considered to stop, ALT and AST at the same time more than 150U and no clinical symptoms of the patient should be terminated anti-tuberculosis treatment. ③ Patients with single AST elevation of 100U or more in chemotherapy should have their liver function rechecked at an interval of about 7d in order to consider the next step of treatment. ④ Liver function should be checked promptly when gastrointestinal symptoms appear in chemotherapy, and anti-tuberculosis should be suspended for patients with elevated ALT accompanied by gastrointestinal symptoms or jaundice. ⑤ HBVM-positive patients should check liver function regularly, and those with major or minor triple positive without other diseases can be included in the scope of chemotherapy. 2. Attaching importance to the time limit of preoperative and postoperative chemotherapy[9] We believe that preoperative anti-tuberculosis chemotherapy for patients requiring surgical treatment should be categorized and treated differently. (1) Patients with good general condition, only patients with simple spinal tuberculosis, no or only mild tuberculosis toxicity, good nutritional status, good function of important organs, 2-3 weeks of anti-tuberculosis drug treatment can be operated. (2) For patients with poor general condition, combined with tuberculosis in other parts of the body, obvious manifestations of tuberculosis toxicity, poor nutritional status, and dysfunction of important organs, the preoperative medication will take a longer time, about 4-6 weeks. (3) For patients with serious systemic tuberculosis poisoning or combined with cornual tuberculosis, the preoperative medication time should be more than 6 weeks. In addition, the preoperative medication time depends on the treatment effect, after systemic supportive therapy and anti-tuberculosis drug treatment, the patient’s general condition improves. Preoperative preparation should be based on the principle that the patient can tolerate surgery. Patients with combined paraplegia should be operated urgently to relieve nerve compression and restore function if paraplegia worsens during anti-tuberculosis treatment. Perioperative H and R should be administered intravenously in order to improve patients’ compliance with medication and reduce gastrointestinal side effects. Postoperative anti-tuberculosis drug treatment involves the choice of the overall chemotherapy program, regardless of the choice of chemotherapy program, must be implemented in accordance with the principles and methods of chemotherapy. Before stopping postoperative chemotherapy, we must achieve the following: normalization of general condition, disappearance of abscess, sinus tract, dead bone and cavity, close setting of bone graft interface, no resorption of bone graft or signs of healing, secure internal fixation, and normalization of ESR and CPR. 3. In recent years, some scholars in China have proposed CT-guided percutaneous puncture tube placement and local minimally invasive removal of lesions and placement of drainage tubes for anti-tuberculosis drug flushing and local anti-tuberculosis drug chemotherapy [10]. We believe that it can be used in patients with senile spinal tuberculosis, multi-vertebral tuberculosis, vertebral tuberculosis combined with paravertebral abscesses, and fluid-filled abscesses. In the application, attention should be paid to (1) strict aseptic operation, observing the technical methods of abscess placement and drainage to avoid the occurrence of general bacterial infection and sinus tract formation. (2) Carefully operate under CT guidance to avoid damage to blood vessels, nerves and important surrounding organs. (3) Pay attention to the dosage accumulation of local anti-tuberculosis drugs and systemic drugs to reduce the occurrence of toxic side effects of anti-tuberculosis drugs. (4) Minimally invasive and local placement of tubes and flushing drug injection treatment can not replace systemic anti-tuberculosis drugs and open surgical treatment. Patients with spinal tuberculosis whose bone destruction seriously affects spinal stability, obvious posterior synostosis deformity and nerve compression still need open surgery. 4. Emphasize the application of DOTS strategy in patients with spinal tuberculosis, and improve the drug compliance of patients with spinal tuberculosis. The management of patients’ chemotherapy is one of the key links to the success or failure of treatment. Only when patients adhere to regular medication and complete the prescribed course of treatment can we achieve the goals of curing the disease, eliminating the source of infection and interrupting the epidemic, and protecting the healthy population. Directly observed treatment, short course (DOTS) strategy is currently recommended by WHO for global TB control. DOTS requires patients to take the medication every time, and it is usually carried out by healthcare workers during hospitalization, or by family members of the patient who can really take responsibility for it during home treatment. to carry out. Healthcare professionals should focus on strengthening health education for patients and their families, so that they can recognize the importance of regular and complete medication taking, and improve medication adherence of spinal tuberculosis patients. In conclusion, anti-tuberculosis drug treatment for spinal tuberculosis plays a decisive role in the cure of spinal tuberculosis patients, and it is important to formulate personalized chemotherapy programs according to the specific conditions of each patient, adhere to the original principle of “early, combined, appropriate amount, regular and full use of sensitive drugs”, and combine nutritional support, strengthen immunity and surgical treatments, so as to improve the cure rate of spinal tuberculosis. The cure rate of spinal tuberculosis is improved by combining nutritional support, strengthening immunization and surgery.