Basic principles of antimicrobial drug application
The application of antimicrobial drugs involves all clinical departments, and the correct and reasonable application of antimicrobial drugs is the key to improve the efficacy, reduce the incidence of adverse reactions and reduce or slow down the occurrence of bacterial drug resistance. The rational clinical application of antimicrobial drugs mainly lies in the following two aspects: (1) whether there are indications for the application of antimicrobial drugs; (2) whether the species selected and the drug delivery scheme are correct and reasonable.
I. Therapeutic application of antimicrobial drugs Xu Xinbao, Department of Hepatobiliary Surgery, Air Force General Hospital
(A) the diagnosis of bacterial infection, the party has the indication to apply antibacterial drugs.
(1) According to the patient’s symptoms, signs and laboratory test results such as blood and urine routine, those who are initially diagnosed as bacterial infection and those who are confirmed as bacterial infection by pathogenic examination are indicated to apply antimicrobial drugs.
2. Infections caused by pathogenic microorganisms such as fungi, Mycobacterium tuberculosis, non-tuberculous mycobacteria, mycoplasma, chlamydia, spirochetes, rickettsia and some protozoa are also indicated for the application of antibacterial drugs.
3. Lack of evidence of infection by bacteria and the above pathogenic microorganisms, the diagnosis cannot be established, as well as viral infections, there is no indication for the application of antibacterial drugs.
(2) Identify the cause of infection as soon as possible, and select antibacterial drugs according to the type of pathogen and the results of bacterial drug sensitivity test.
In principle, the selection of antimicrobial drugs should be based on the type of pathogenic bacteria and the results of antimicrobial susceptibility testing of pathogenic bacteria.
1. Inpatients must take the corresponding specimens before starting antibacterial treatment and send them to bacterial culture immediately to clarify the pathogenic bacteria and drug sensitivity results as soon as possible; outpatients can send bacterial culture and drug sensitivity test according to their condition.
2. In critical patients, before the pathogenic bacteria and drug sensitivity results are known, the most likely pathogenic bacteria can be inferred according to the patient’s morbidity, location, primary lesion, underlying disease, etc., and the local bacterial resistance status can be combined with the empirical treatment of antibacterial drugs first, and after the bacterial culture and drug sensitivity results are known, the drug regimen can be adjusted according to the drug sensitivity results for patients with poor efficacy.
(c) Select drugs according to the characteristics of their antibacterial effects and their in vivo processes.
The pharmacodynamics (antibacterial spectrum and antibacterial activity) and pharmacokinetics (absorption, distribution, metabolism and excretion processes) of various antibacterial drugs are different, so they have different clinical indications (see Part IV). Clinicians should select antimicrobial drugs according to the above-mentioned characteristics of various antimicrobial drugs and according to the clinical indications.
(D) The antimicrobial drug treatment plan should be formulated based on the patient’s condition, the type of pathogenic bacteria and the characteristics of antimicrobial drugs.
According to the pathogenic bacteria, the site of infection, the severity of infection and the patient’s physiological and pathological conditions to develop antibacterial drug treatment plan, including the choice of antibacterial drug species, dose, the number of doses, route of administration, the course of treatment and the combination of drugs. The following principles should be followed when formulating the treatment plan.
1. species selection: select antimicrobial drugs according to the type of pathogenic bacteria and drug sensitivity results. 2.
2. Dosage: administered according to the therapeutic dose range of various antibacterial drugs. For the treatment of severe infections (such as sepsis, infective endocarditis, etc.) and infections in areas not easily reached by antimicrobial drugs (such as central nervous system infections, etc.), a larger dose of antimicrobial drugs is appropriate (high limit of therapeutic dose range); while for the treatment of simple lower urinary tract infections, a smaller dose can be applied (low limit of therapeutic dose range) because the urine concentration of most drugs is much higher than the blood concentration.
3. Route of administration.
(1) For mild infections that can receive oral administration, orally absorbed antimicrobial drugs should be used, and intravenous or intramuscular administration is not necessary. Patients with severe infections and systemic infections should be given intravenous medication for initial treatment to ensure efficacy; when the condition improves and can be given orally, the medication should be switched to oral administration as early as possible.
(2) Local application of antibacterial drugs should be avoided as much as possible. Local application of antibacterial drugs should be avoided when treating systemic infection or organ infection. The species mainly for systemic application should be avoided for local use. 4.
4. The number of doses: 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 (with the exception of severe infections).
5. Duration of treatment: generally until the body temperature is normal and the symptoms subside 72-96 hours later. However, sepsis, infective endocarditis, septic meningitis, typhoid fever, brucellosis, osteomyelitis, hemolytic streptococcal pharyngitis and tonsillitis, deep fungal disease, tuberculosis, etc. require a longer course of treatment to completely cure and prevent recurrence.
6. Combination of antibacterial drugs: there must be clear indications, single drug can effectively treat the infection, should not be used in combination, only in the following cases when there are indications for the combination of drugs.
(1) serious infections in which the pathogenic bacteria have not been identified, including serious infections in immunodeficient individuals.
(2) Mixed aerobic and anaerobic infections, infections with 2 or more pathogens that cannot be controlled by a single antimicrobial drug.
(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 in which the pathogenic bacteria are prone to develop resistance to certain antimicrobial drugs, such as tuberculosis and deep fungal diseases.
(5) Drugs with synergistic antibacterial effects can be used in combination, such as penicillins, cephalosporins and other β-lactams and aminoglycosides. The combination of two drugs is usually used, and the combination of three or more drugs is only applicable to individual cases, such as the treatment of tuberculosis. In addition, it must be noted that the combination of drugs will increase the adverse drug reactions.
Second, the preventive application of antibacterial drugs
(A) the preventive application of antibacterial drugs in the field of internal medicine and pediatrics
1. 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 the invasion of any bacteria, it is often ineffective.
2. Prevention of infections that occur over a period of time may be effective; long-term prophylactic use often fails to achieve the goal.
3. If the patient’s primary disease can be cured or remitted, prophylaxis may be effective. If the primary disease cannot be cured or remitted (e.g., immunodeficient patients), prophylactic drugs should be used sparingly or not at all. For immunodeficient patients, it is advisable to closely observe their condition and, once signs of infection appear, to give empirical treatment first while sending the relevant specimens for culture.
4. The cases in which the routine prophylactic application of antibacterial drugs is usually inappropriate: common cold, measles, chickenpox and other viral diseases, coma, shock, poisoning, heart failure, tumors, application of adrenocorticotropic hormones and other patients.
(B) Preventive application of antimicrobial drugs during surgical procedures
1) The purpose of preventive medication: to prevent surgical site infection, including incisional infection and infection of organs and cavities involved in surgery, but not including systemic infection that may occur after surgery without direct relationship with surgery.
2. Basic principles of medication: according to whether the surgical field is contaminated or contaminated, decide whether to prevent the use of antibacterial drugs.
(1) Clean surgery: The surgical field is a sterile part of the body, with no local inflammation or injury, and does not involve the respiratory tract, gastrointestinal tract, genitourinary tract and other organs of the body that are connected to the outside world. The surgical field is not contaminated and usually does not require antimicrobial prophylaxis. Prophylaxis can only be considered in the following cases: (1) large scope of surgery, long duration and increased chance of contamination; (2) surgery involving important organs, which will cause serious consequences once infection occurs; (3) foreign body implantation surgery; (4) high-risk groups such as the elderly or immunodeficient persons.
(2) Clean – contaminated surgery: upper and lower respiratory tract, upper and lower gastrointestinal tract, genitourinary tract surgery, or surgery via the above organs, due to the presence of a large number of human parasitic flora at the surgical site, the surgery may contaminate the surgical field to cause infection, the need to prevent the use of antibacterial drugs.
(3) Contaminated surgery: Surgery that has caused serious contamination of the surgical field due to large spillage of body fluids from the gastrointestinal tract, urinary tract, biliary tract or open trauma without dilation. This kind of surgery needs preventive antibacterial drugs.
Pre-operative surgery with bacterial infection is a therapeutic application of antimicrobial drugs and does not belong to the category of preventive application.
3. Drug selection.
(1) To prevent postoperative incisional infection, drugs should be selected for Staphylococcus aureus.
(2) Prevention of organ-cavity infections should be based on the type of contamination or possible contaminating bacteria in the surgical field, and refer to the hospital’s bacterial resistance status to select species. Such as colon or rectal surgery before the selection of antibacterial drugs should be effective against Escherichia coli and Bacteroides fragilis.
4. Drug administration method.
(1) For those who receive clean surgery, the drug should be given 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 contaminating the surgical field during surgery has been reached in the local tissue when the surgical incision is exposed. If the duration of surgery exceeds 3 hours, or if blood loss is high (>1500 ml), a second dose may be given intraoperatively (except for those using long half-life antimicrobials). The effective duration of antimicrobial coverage 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. One dose of preoperative medication is sufficient for clean surgical procedures of short duration (< 2 hours).
(2) For clean and contaminated surgeries, the duration of prophylaxis is also 24 hours, which can be extended to 48 hours if necessary. Contaminated surgery can be extended according to the patient’s condition. For those with pre-existing infection before surgery, the duration of antimicrobial use should be determined by therapeutic application.