The first part is the basic principles of clinical application of antibacterial drugs.

The application of antibacterial drugs involves various clinical departments. Correct and rational use of antibacterial drugs is the key to improve the curative effect, reduce the incidence of adverse reactions and reduce or slow down the occurrence of bacterial drug resistance. Whether the clinical application of antibacterial drugs is correct and reasonable is based on the following two aspects: (1) whether there are indications for using antibacterial drugs; (2) Whether the selected varieties and administration schemes are correct and reasonable.

Basic principles of antimicrobial therapy and application

First, the diagnosis of bacterial infection, there are indications for the use of antibacterial drugs.

According to the patient's symptoms, signs, blood and urine routine test results, the use of antibacterial drugs was prompted only after the initial diagnosis of bacterial infection and pathogen examination confirmed bacterial infection; Infections caused by pathogenic microorganisms such as fungi, mycobacterium tuberculosis, nontuberculous mycobacteria, mycoplasma, chlamydia, spirochetes, rickettsia and some protozoa also need to use antibacterial drugs. Lack of evidence of bacterial infection and the above-mentioned pathogenic microorganisms, who can not be diagnosed, virus-infected people have no indications to use antibacterial drugs.

Second, find out the infected pathogens as soon as possible, and choose antibacterial drugs according to the types of pathogens and the results of bacterial drug sensitivity tests.

In principle, the selection of antibacterial drugs should be based on the types of pathogenic bacteria and the results of bacterial drug sensitivity test (hereinafter referred to as drug sensitivity). Therefore, in qualified medical institutions, inpatients must collect corresponding specimens and send them to bacterial culture immediately before starting antibacterial treatment, so as to make clear the pathogenic bacteria and drug sensitivity results as soon as possible; Outpatients can carry out drug sensitivity work according to the needs of their illness.

Before knowing the pathogenic bacteria and drug sensitivity results, critically ill patients can infer the most likely pathogenic bacteria according to their incidence, location, primary focus and basic diseases. Combined with the local bacterial resistance, empirical antibacterial drugs were given. After understanding the results of bacterial culture and drug sensitivity, adjust the dosage regimen for patients with poor curative effect.

Third, according to the characteristics of antibacterial action of drugs and their in vivo process characteristics, choose drugs.

The pharmacodynamics (antibacterial spectrum and antibacterial activity) and pharmacokinetics (absorption, distribution, metabolism and excretion) of various antibacterial drugs are different, so they have different clinical indications. Clinicians should correctly select antibacterial drugs according to the above characteristics and clinical indications (see "Indications and Precautions of Various Antibacterials").

Four, antimicrobial therapy should be based on the patient's condition, the types of pathogens and the characteristics of antimicrobial agents.

According to the pathogenic bacteria, infection site, infection severity and patient's physiological and pathological conditions, the treatment scheme of antibacterial drugs was formulated, including the selection, dosage, administration times, administration route, course of treatment and combined medication of antibacterial drugs. The following principles should be followed when making a treatment plan.

(1) Variety selection: Antibacterials are selected according to the types of pathogenic bacteria and drug sensitivity results.

(2) Dosage: Administration according to the therapeutic dosage range of various antibacterial drugs. It can be used for treating serious infections (such as septicemia and infective endocarditis) and infections in parts where antibiotics are not easy to reach (such as central nervous system infection). ), the dose of antibiotics should be large (the upper limit of the therapeutic dose range); When treating simple lower urinary tract infection, because the urine concentration of most drugs is much higher than the blood concentration, a smaller dose (the lower limit of the therapeutic dose range) can be applied.

(3) Administration route:

1. For mild infections that can be taken orally, fully absorbed antibacterial drugs should be taken orally instead of intravenous or intramuscular injection. The initial treatment of patients with severe infection and systemic infection should be given intravenous injection to ensure the curative effect; When the condition improves and can be taken orally, it should be taken orally as soon as possible.

2. Local application of antibacterial drugs should be avoided as far as possible: after local application of antibacterial drugs to skin and mucosa, they are rarely absorbed, and the effective concentration cannot be reached at the infected site, which may easily cause allergic reactions or lead to the generation of drug-resistant bacteria. Therefore, local application of antibacterial drugs should be avoided when treating systemic infection or organ infection. The local application of antibacterial drugs is limited to a few cases, such as when it is difficult to reach the therapeutic concentration at the infected site after systemic administration, local drugs can be added as adjuvant treatment. This situation can be seen in the treatment of central nervous system infection, when some drugs can be administered intrathecally at the same time; Injection of antibacterial drugs into abscess cavity of encapsulated thick-walled abscess and local medication for eye infection. Some infections on the surface of oral cavity, vagina and other skin mucosa can be applied locally or externally, but the varieties mainly used for systemic application should be avoided as local drugs. Topical medication should use fungicides that are less irritating, not easy to absorb, not easy to produce drug resistance, and not easy to cause allergic reactions. Penicillins, cephalosporins and other drugs that easily cause allergic reactions should not be used locally. Otototoxic drugs such as aminoglycosides should not be dripped locally.

(4) Dosage: In order to ensure the maximum efficacy of the drug in vivo and kill the pathogenic bacteria in the infected focus, the drug should be administered according to the principle of combining pharmacokinetics and pharmacodynamics. Penicillins, cephalosporins and other beta lactams, erythromycin, clindamycin and so on. The short elimination half-life should be given many times in one day. Fluoroquinolones and aminoglycosides can be administered once a day (except for severely infected people).

(5) Course of treatment: The course of treatment of antibacterial drugs varies with different infections. Generally, the body temperature is normal, and the symptoms subside for 72-96 hours. Under special circumstances, it should be handled properly. Sepsis, infective endocarditis, purulent meningitis, typhoid fever, brucellosis, osteomyelitis, hemolytic streptococcal pharyngitis and tonsillitis, deep mycosis, tuberculosis, etc. all need a long course of treatment to be completely cured and prevent recurrence.

(6) There should be clear indications for the combined use of antibacterial drugs: infections that can be effectively treated by a single drug do not need to be combined with drugs, and only when there are indications for combined drugs need to be combined with drugs.

1. Serious infection of unknown protozoa, including severe infection of immunocompromised people.

2. Mixed infection of aerobic bacteria and anaerobic bacteria, and infection of two or more pathogens that cannot be controlled by a single antibacterial drug.

3. Serious infections such as infective endocarditis or septicemia that cannot be effectively controlled by a single antibacterial drug.

4. Long-term treatment is needed, but pathogens are susceptible to infections resistant to certain antibacterial drugs, such as tuberculosis and deep fungal diseases.

5. Due to the synergistic antibacterial effect of drugs, the dosage of highly toxic antibacterial drugs should be reduced when combined with drugs. For example, when amphotericin B is combined with flucytosine in the treatment of cryptococcal meningitis, the dosage of amphotericin B can be appropriately reduced, thus reducing its toxic reaction. Combination drugs with synergistic or additive antibacterial effects should be selected, such as β -lactams such as penicillin and cephalosporin combined with aminoglycosides, and amphotericin B combined with flucytosine. Usually, the combination of two drugs is used, and the combination of three or more drugs is only suitable for individual cases, such as tuberculosis. In addition, it must be noted that adverse drug reactions will increase after the combination of drugs.

Basic principles of preventive application of antibacterial drugs

First, preventive medicine in internal medicine and pediatrics.

1. It can effectively prevent infection caused by one or two specific pathogens invading the body; If the purpose is to prevent any bacterial invasion, it is often ineffective.

2. It may be effective to prevent infections that occur within a period of time; Long-term preventive medication often fails to achieve the goal.

3. If the patient's primary disease can be cured or alleviated, preventive medication may be effective. If the primary disease cannot be cured or alleviated (such as immunodeficiency), preventive drugs should be used as little as possible. Patients with immunodeficiency should be closely observed, and once there are signs of infection, relevant specimens should be sent for culture and experience treatment first.

4. Usually it is not suitable for routine preventive application of antibacterial drugs: patients with common cold, measles, chickenpox and other viral diseases, coma, shock, poisoning, heart failure, tumor, application of adrenocortical hormone, etc.

Second, preventive medication for surgery.

(1) Prophylactic medication for surgical operation Objective: To prevent postoperative incision infection, clean or polluted surgical site infection and possible postoperative systemic infection.

(2) The basic principle of preventive medication in surgical operation: According to whether the surgical field is polluted or may be polluted, decide whether to use antibacterial drugs for prevention.

1. clean surgery: the operating field is a sterile part of the human body, without local inflammation or injury, and does not involve respiratory tract, digestive tract, urogenital tract and other organs communicating with the outside world. There is no pollution in the operating field, and preventive antibiotics are usually not needed. Prophylactic antibiotics can only be considered in the following situations: (1) The scope of operation is large, the time is long, and the chance of pollution is increased; (2) Surgery involves important organs, and once infection occurs, it will cause serious consequences, such as head surgery, heart surgery, intraocular surgery, etc. (3) foreign body implantation, such as artificial heart valve implantation, permanent pacemaker implantation, artificial joint replacement, etc. ; (4) High-risk groups such as the elderly or immunocompromised people.

2. Clean pollution surgery: upper and lower respiratory tract, upper and lower digestive tract, urogenital tract surgery, or surgery through the above organs, such as major oropharyngeal surgery, vaginal hysterectomy, transrectal prostate surgery, open fracture or trauma surgery. Because there are a large number of human colonization flora in the operation site, it may pollute the operation field and cause infection during the operation. Antibacterials should be used to prevent this kind of operation.

3. Contaminated surgery: surgery that seriously pollutes the surgical field due to a large amount of body fluids or unexpanded open wounds in the gastrointestinal tract, urinary tract and biliary tract. This operation requires preventive use of antibacterial drugs.

Surgery with bacterial infection before operation, such as peritonitis caused by perforation of abdominal organs, abscess resection, amputation of gas gangrene, etc. It belongs to the therapeutic application of antibacterial drugs, not to the category of preventive application.

4. Selection and administration of antibacterial drugs for surgical prevention: The selection of antibacterial drugs depends on the purpose of prevention. In order to prevent postoperative wound infection, the drug should be Staphylococcus aureus (hereinafter referred to as Staphylococcus aureus). In order to prevent surgical site infection or systemic infection, it is necessary to choose according to the kinds of bacteria that are polluted or may be polluted in the surgical field. For example, antibiotics that are effective against Escherichia coli and Bacteroides fragilis should be selected before colon or rectal surgery. Antibacterial drugs must be selected with definite curative effect, safety, convenient use and relatively low price.

Administration method: clean surgery patients should be administered within 0.5 ~ 2 hours before operation or at the beginning of anesthesia, so that local tissues can reach the drug concentration enough to kill bacteria invading the incision during operation when the incision is exposed. If the operation time exceeds 3 hours or the blood loss is large (> 1500 ml), the second dose can be given during the operation. The effective coverage time of antibacterial drugs should include the whole operation process and 4 hours after operation, and the total preventive drug use time should not exceed 24 hours, which can be extended to 48 hours in some cases. Short operation time (

Basic principles of antimicrobial application under special pathophysiological conditions

1. Application of Antibacterials in Patients with Renal Insufficiency (see Table 1. 1)

(1) Basic principles: Many antibacterial drugs are excreted in human body mainly through the kidneys, while some antibacterial drugs are nephrotoxic. The principles of applying antibacterial drugs to infected patients with renal insufficiency are as follows.

1. Try to avoid using nephrotoxic antibacterial drugs, and when there are indications for application, the dosage regimen must be adjusted.

2. According to the severity of infection, the types of pathogenic bacteria and the results of drug sensitivity test, choose antibiotics with no or low nephrotoxicity.

3. Adjust the dosage and method of administration according to the degree of renal insufficiency of patients and the excretion route of antibacterial drugs in human body.

(II) Selection of Antibacterials and Adjustment of Administration Scheme: According to the in vivo process characteristics and nephrotoxicity of antibiotics, the selection of antibiotics in renal failure is as follows.

1. Antibacterials mainly excreted by the hepatobiliary system or metabolized by the liver, or excreted by the kidney and hepatobiliary system at the same time are used in patients with renal insufficiency, and the original therapeutic dose or dose is slightly reduced.

2. Antibacterials that are mainly excreted by the kidney and have no nephrotoxicity or slight nephrotoxicity can be used for patients with renal insufficiency, but the dosage needs to be adjusted appropriately.

3. Patients with renal insufficiency should avoid using nephrotoxic antibiotics. If there are indications for the use of such drugs, it is necessary to monitor the blood drug concentration in order to adjust the administration plan and realize individualized administration; It can also be reduced according to the degree of renal insufficiency (based on the endogenous creatinine clearance rate), and the patient's renal function should be closely monitored during treatment.

Second, the use of antibiotics in patients with abnormal liver function (see table 1.2)

The selection and dosage adjustment of antibacterial drugs under the condition of liver dysfunction need to consider the influence of liver dysfunction on the internal process of these drugs and the possibility of toxic reactions of these drugs and their metabolites under the condition of liver dysfunction. Because the metabolic process of drugs in the liver is complex, the metabolic process of many drugs in the body has not been fully clarified. According to the available data, the application of antibacterial drugs in abnormal liver function has the following situations.

1. Drugs mainly cleared by the liver decreased obviously when the liver function decreased, but there was no obvious toxic reaction. It can still be used normally in liver diseases, but the dosage should be reduced when necessary, and the liver function should be closely monitored during treatment. Macrolides such as erythromycin (ester-free), lincomycin and clindamycin belong to this category.

2. Drugs are mainly eliminated or metabolized by the liver or a considerable number of livers. When the liver function declines, the elimination is reduced, which may lead to toxic reactions. Patients with decreased liver function should avoid using such drugs, such as chloramphenicol, rifampicin and erythromycin esters.

3. Drugs are cleared through the liver and kidney, and the clearance rate of drugs in patients with hepatic insufficiency decreases, and the blood drug concentration increases, especially in patients with renal insufficiency, but the drugs themselves are not toxic. Patients with severe liver disease, especially those with decreased liver and kidney function, need to reduce the use of such drugs. Penicillins and cephalosporins excreted through the kidney and liver belong to this situation.

4. Drugs are mainly excreted by the kidneys, and patients with hepatic insufficiency do not need to adjust the dose. Aminoglycoside antibiotics belong to this category.

Third, the application of antibacterial drugs in elderly patients

Due to the physiological degeneration of tissues and organs, the immune function of the elderly has also declined. Once infected, the application of antibacterial drugs should pay attention to the following matters.

1. The renal function of the elderly is decreased physiologically. When receiving antibiotics excreted mainly through the kidney at the usual dose, adverse drug reactions are easy to occur because the drug excretion from the kidney is reduced, the drug accumulates in the body and the blood drug concentration is increased. Therefore, elderly patients, especially elderly patients, should receive antibiotics mainly excreted by the kidney, which should be reduced according to mild renal insufficiency, which can be 2/3 ~ 1/2 of the normal treatment. Most penicillins, cephalosporins and other β -lactams are the same.

2. Elderly patients should choose antibacterial drugs with low toxicity and strong bactericidal effect, and β -lactams such as penicillins and cephalosporins are commonly used drugs. The use of highly toxic drugs such as aminoglycosides, vancomycin and norvancomycin should be avoided as far as possible. When there are clear application indications, it should be used with caution under close observation. At the same time, the blood concentration should be monitored, and the dosage should be adjusted accordingly, so as to achieve the goal of safe and effective medication.

Fourth, the application of antibacterial drugs in neonatal patients

Some important organs in the neonatal period are not fully developed, during which their growth and development change rapidly with age, so the following matters should be paid attention to when using antibacterial drugs for neonatal infection.

1. In the neonatal period, the liver and kidney are immature, the secretion of liver enzymes is insufficient or lacking, and the renal clearance function is poor. Therefore, the use of highly toxic antibacterial drugs, including aminoglycosides, vancomycin, norvancomycin and so on. Chloramphenicol is mainly excreted by the kidney and metabolized by the liver, so it should be avoided when newborns are infected. When there are indications for application, it is necessary to monitor the blood drug concentration, adjust the administration plan accordingly, and give drugs individually to ensure the safety and effectiveness of treatment. If the blood drug concentration cannot be monitored, the above drugs should not be selected.

2. Avoid using or stopping antibiotics that may cause serious adverse reactions in the neonatal period (see table 1.3). Tetracyclines and quinolones that can affect the growth and development of newborns are prohibited, and sulfonamides and furans that can cause nuclear jaundice and hemolytic anemia are avoided.

3. Due to the imperfect renal function in the neonatal period, it is necessary to reduce the β -lactam drugs such as penicillins and cephalosporins mainly excreted through the kidneys in order to prevent drugs from accumulating in the body and causing serious toxic reactions in the central nervous system.

4. The weight, tissues and organs of newborns are becoming more and more mature, and the pharmacokinetics of antibacterial drugs in newborns also changes with age, so the dosage regimen should be adjusted according to age when using antibacterial drugs.

Five, the application of antibacterial drugs in children.

Pediatric patients should pay attention to the following points when applying antibacterial drugs:

1. aminoglycoside antibiotics: These drugs have obvious ototoxicity and nephrotoxicity, so children should avoid using them. Only when there are clear indications for clinical application and there are no other low-toxic antibacterial drugs to choose from, can this kind of drugs be selected, and the adverse reactions should be closely observed during the treatment. If conditions permit, the blood drug concentration should be monitored and individualized medication should be given according to the results.

2. Vancomycin and norvancomycin: These drugs also have certain nephrotoxicity and ototoxicity, and children can only choose them if there are clear indications. During the treatment, the adverse reactions should be closely observed, the blood drug concentration should be monitored, and individualized administration should be carried out.

3. Tetracycline antibiotics: can cause yellowing of teeth and hypoplasia of enamel. Not suitable for children under 8 years old.

4. Quinolones antibacterial drugs: Minors under the age of 18 should avoid using these drugs because of their possible adverse effects on bone development.

Application of intransitive verbs antibacterial drugs in pregnant and lactating patients

(1) Application of antibacterial drugs in pregnant women (see table 1.4): The application of antibacterial drugs in pregnancy should consider the influence of drugs on both mother and fetus.

1. If it has teratogenic or obvious toxic effects on the fetus, such as tetracyclines and quinolones, it should be avoided during pregnancy.

2. Those who have toxic effects on the mother and fetus, such as aminoglycosides, vancomycin and norvancomycin. Avoid during pregnancy; When there are indications for application, it must be used under the monitoring of blood drug concentration to ensure the safety and effectiveness of medication.

3. The drug has low toxicity, no obvious influence on fetus and mother, and no teratogenic effect. It can be used if it is infected during pregnancy. This is the case with β lactams such as penicillins and cephalosporins and fosfomycin.

The US Food and Drug Administration (FDA) classifies drugs into categories A, B, C, D and X according to their risks during pregnancy, which can be used as a reference for drug selection (see table 1.4).

(2) Application of antibacterial drugs in lactating patients: After receiving antibacterial drugs, lactating patients can secrete drugs from breast milk. Usually, the drug content in breast milk is not high, which does not exceed 65,438+0% of the daily dosage of lactating patients; A few drugs are highly secreted in milk, such as fluoroquinolones, tetracyclines, macrolides, chloramphenicol, sulfamethoxazole, trimethoprim and metronidazole. The content of β -lactams and aminoglycosides such as penicillins and cephalosporins in milk is low. However, regardless of the drug concentration in milk, it has a potential impact on infants and may have adverse reactions. For example, aminoglycoside antibiotics can cause hearing loss in infants, chloramphenicol can cause bone marrow suppression in infants, sulfamethoxazole can cause nuclear jaundice and hemolytic anemia, tetracycline can cause yellow staining of deciduous teeth, and penicillin can cause allergic reactions. Therefore, aminoglycosides, quinolones, tetracyclines, chloramphenicol and sulfonamides should be avoided when treating lactating patients. Breast-feeding patients should stop breastfeeding when using any antibacterial drugs.