Basic principles of antimicrobial drug application The application of antimicrobial drugs involves various clinical departments, and the correct and rational application of antimicrobial drugs is the key to improve the therapeutic efficacy, reduce the incidence of adverse reactions, and reduce or slow down the occurrence of bacterial resistance. The rational application of antimicrobial drugs in the clinic mainly lies in the following two aspects: (1) whether there are indications for the application of antimicrobial drugs; (2) whether the selected varieties and drug delivery programs are correct and reasonable. First, the therapeutic application of antimicrobial drugs Air Force General Hospital Hepatobiliary Surgery Xu Xinbao (a) diagnosis of bacterial infections, the party has indications for the application of antimicrobial drugs. (1) According to the patient’s symptoms, signs and symptoms of blood, urine and other laboratory test results, the preliminary diagnosis of bacterial infection and the pathogenic examination of bacterial infections will have the indication to apply antimicrobial drugs. 2. Infections caused by fungi, Mycobacterium tuberculosis, non-tuberculosis mycobacteria, mycoplasma, chlamydia, spirochetes, rickettsiae, and some protozoa and other pathogenic microorganisms are also eligible for the application of antimicrobial drugs. 3. Lack of evidence of bacterial and the above pathogenic microorganisms infection, the diagnosis can not be established, as well as viral infections, there is no indication for the application of antimicrobial drugs. (ii) Identify the pathogen of infection as early as possible, and select antimicrobial drugs according to the type of pathogen and the results of bacterial drug sensitivity test. In principle, the selection of antibacterial drugs should be based on the type of pathogenic bacteria and the results of antibacterial drug susceptibility testing of pathogenic bacteria. 1. Before starting antimicrobial treatment, hospitalized patients should take the corresponding specimens and send them for bacterial culture immediately, so as to clarify the pathogenic bacteria and drug sensitivity results as soon as possible; outpatients can be sent for bacterial culture and drug sensitivity test according to the needs of their condition. (2) Before the critical patients are informed of the pathogenic bacteria and drug sensitivity results, the most probable pathogenic bacteria can be deduced according to the patient’s morbidity, morbidity site, primary lesions, underlying diseases, etc., and combined with the local bacterial drug resistance status, antibacterial drugs can be given to empirical treatment first, and after the results of the bacterial culture and drug sensitivity results are known, the drug administration program can be adjusted according to the results of the drug sensitivity for the patients with unsatisfactory therapeutic effect. (iii) Selection of drugs according to the characteristics of their antibacterial effects and their in vivo processes. Various antibacterial drugs have different pharmacodynamics (antibacterial spectrum and antibacterial activity) and pharmacokinetics (absorption, distribution, metabolism and excretion), and therefore have different clinical indications (see Part IV). Clinicians should use antimicrobial drugs according to the above characteristics of various antimicrobial drugs and correctly select antimicrobial drugs according to clinical indications. (D) Antimicrobial drug treatment program should be comprehensively formulated based on the patient’s condition, the type of pathogenic bacteria and the characteristics of antimicrobial drugs. According to the pathogenic bacteria, infection site, infection severity and the patient’s physiological and pathological conditions to develop antimicrobial drug treatment program, including antimicrobial drugs, including the selection of varieties, dosage, number of times of administration, route of administration, course of treatment and combination of drugs. The following principles should be followed when formulating the treatment program. 1. species selection: according to the type of pathogenic bacteria and drug sensitivity results of the selection of antimicrobial drugs. 2. Dosage: according to the therapeutic dosage range of various antibacterial drugs. For the treatment of severe infections (e.g. sepsis, infective endocarditis, etc.) and infections in areas not easily reached by antimicrobial drugs (e.g. central nervous system infections, etc.), the dose of antimicrobial drugs should be larger (high limit of therapeutic dose range); and for the treatment of simple lower urinary tract infections, as the concentration of most drugs in the urine is much higher than that in the blood, a smaller dose can be applied (low limit of therapeutic dose range). 3. Route of administration: (1) For mild infections that can be administered orally, antibacterial drugs that are fully absorbed orally should be used, without the need for intravenous or intramuscular injection. Serious infections, systemic infections, the initial treatment of patients should be given to the intravenous drug to ensure the effectiveness of the drug; when the condition improves and can be taken orally, it should be switched to oral drug delivery as soon as possible. (2) Local application of antibacterial drugs should be avoided as much as possible, and local application of antibacterial drugs should be avoided when treating systemic infection or organ infection. Species mainly for systemic application should be avoided as localized drugs. 4. Frequency of administration: The drugs should be administered according to the principle of combining pharmacokinetics and pharmacodynamics. Penicillins, cephalosporins and other endocannabinoids, erythromycin, clindamycin, etc. have a short elimination half-life and should be administered several times a day. Fluoroquinolones, aminoglycosides, etc. should be given once a day (except for severe infections). 5. Duration of treatment: generally used until the body temperature is normal, symptoms subside after 72 to 96 hours. However, sepsis, infective endocarditis, purulent meningitis, typhoid fever, brucellosis, osteomyelitis, hemolytic streptococcal pharyngitis and tonsillitis, deep fungal disease, tuberculosis, etc. need a longer course of treatment to be completely cured, and prevent recurrence. 6. Combined application of antimicrobial drugs: there must be a clear indication, a single drug can be effective treatment of infection, should not be combined with drugs, only in the following cases when there are indications for combined use of drugs. (1) Serious infections in which the causative agent has not been identified, including serious infections in immunodeficient persons. (2) Mixed aerobic and anaerobic infections that cannot be controlled by a single antimicrobial agent, infections with 2 or more pathogenic bacteria. (3) Serious infections such as infective endocarditis or sepsis that cannot be effectively controlled by a single antimicrobial drug. (4) Infections that require a long course of treatment, but the pathogenic bacteria are prone to be resistant to certain antimicrobial drugs, such as tuberculosis and deep fungal diseases. (5) Drugs with synergistic antimicrobial effects can be used in combination, such as penicillins, cephalosporins and other β-lactams and aminoglycosides. Combination of drugs usually use two kinds of drug combination, three and more than three kinds of drug combination is only applicable to individual cases, such as the treatment of tuberculosis. In addition, it must be noted that the adverse drug reactions will increase after the combination of drugs. Second, the preventive application of antibacterial drugs (a) internal medicine and pediatrics in the field of antibacterial drugs for the prevention of one or two specific pathogenic bacteria invasion of the body caused by infection, may be effective; if the purpose is only to prevent any bacterial invasion, it is often ineffective. 2. Preventing infections that occur over a period of time may be effective; long-term prophylaxis often fails to achieve its purpose. 3. Prophylaxis may be effective if the patient’s primary disease can be cured or in remission. Primary disease can not be cured or remission (such as immunodeficiency), prophylaxis should not be used or used as little as possible. For immunodeficient patients, it is advisable to closely observe their condition, and once signs of infection appear, send the relevant specimens for culture at the same time, and first give empirical treatment. 4. It is usually not suitable for routine prophylactic application of antibacterial drugs: common cold, measles, chickenpox and other viral diseases, coma, shock, poisoning, heart failure, tumors, the application of adrenocorticotropic hormone and other patients. (II) Preventive application of antimicrobials in surgery 1. The purpose of preventive medication: to prevent surgical site infections, including incisional infections and infections of organs and cavities involved in surgery, but excluding systemic infections that are not directly related to the surgery and may occur in the postoperative period. 2. Basic principles of drug administration: according to whether the surgical field is contaminated or contaminated possibly, decide whether to prevent the use of antimicrobial drugs. (1) Clean surgery: the surgical field is a sterile part of the human body, with no local inflammation or injury, and it does not involve the respiratory tract, digestive tract, genitourinary tract, and other organs of the human body that are connected to the outside world. Surgical field is not contaminated, usually do not need prophylactic antimicrobial drugs, only in the following cases can be considered prophylactic drugs ① large scope of the operation, long time, increasing the chance of contamination; ② surgery involves important organs, once the infection will cause serious consequences; ③ foreign object implantation; ④ old age, or immunodeficiency of people and other high-risk groups. (2) Clean – contaminated surgery: upper and lower respiratory tract, upper and lower gastrointestinal tract, genitourinary tract surgery, or surgery through the above organs, due to the presence of a large number of human parasites in the surgical site, the surgery may contaminate the surgical field leading to infections, and need to be prevented with antimicrobial drugs. (3) Contaminated surgery: due to the gastrointestinal tract, urinary tract, biliary tract, body fluids overflow or open trauma without dilatation, etc. has caused serious contamination of the surgical field of the surgery. This type of surgery requires prophylaxis with antibacterial drugs. Preoperative bacterial infection already exists in the surgery, is a therapeutic application of antimicrobial drugs, is not a preventive application category. 3. Drug selection: (1) Prevention of postoperative incisional infections, drugs should be selected for Staphylococcus aureus. (2) Prevention of organ-lumen infections, based on the surgical field contamination or possible contamination of the bacterial species selection, and reference to the hospital’s bacterial resistance status of the selection of varieties. Such as colon or rectal surgery should be used before the selection of effective antimicrobials against Escherichia coli and Mycobacterium fragilis. 4. Method of administration: (1) For those who undergo clean surgery, the drug should be administered within 0.5 to 1 hour before surgery or at the beginning of anesthesia (intravenous administration can be given 0.5 hours before surgery, and intramuscular injection 0.5 to 1 hour before surgery), so that the concentration of the drug sufficient to kill bacteria that contaminate the surgical field during surgery has been reached in the local tissues at the time of exposure of the surgical incision. A second dose may be given during surgery (except for those using long half-life antimicrobials) if the surgery lasts more than 3 hours or if blood loss is significant (>1500 ml). Effective coverage of antimicrobials should include the entire surgical procedure and 4 hours after the end of the procedure, with the total duration of prophylaxis not exceeding 24 hours, which may be extended to 48 hours in individual cases. For clean surgeries of short duration (< 2 hours), one dose of preoperative medication is sufficient. (2) For clean-contaminated procedures, the duration of prophylaxis should also be 24 hours, or 48 hours if necessary. Contaminated surgery can be extended according to the patient's situation. For those with pre-existing infections, the duration of antimicrobial use should be based on therapeutic application.