At present, there are many varieties of antibiotics used in clinical practice, which can be categorized into ten major groups according to their chemical structures.
Beta-lactams are the most varied and widely used antibiotics in the treatment of a wide range of diseases, and they are the most effective anti-infective drugs, as well as the main force of antibiotics.
This class of drugs mainly includes two parts:
①Penicillin, this is the earliest β-lactam, its efficacy is accurate, low price, commonly used varieties of penicillin sodium salt or potassium salt, ampicillin sodium (ampicillin sodium), piperazine penicillin (piperacillin sodium), hydroxybenzylpenicillin (amoxicillin) and so on.
②Cephalosporins, these drugs have high efficacy, low toxicity, less allergic reactions than penicillin, widely used in various types of infectious diseases, commonly used varieties of cephalosporin (Pioneer Ⅳ), cefazolin sodium (Pioneer Ⅴ), cefradine (Pioneer Ⅵ), ceftriaxone sodium (Bacteriophage) and so on.
Aminoglycosides (glycosides) commonly used varieties of streptomycin, gentamicin, kanamycin, small nosocomial (small nosocomial), acemicin (acemicin) and so on. doxycycline (doxycycline), doxycycline (doxycycline) and so on.
Chloramphenicol commonly used varieties are chloramphenicol, methylsulfonylmethamphenicol, and so on.
Macrolides commonly used varieties are erythromycin, erythromycin, erythromycin sulfate, madithromycin, acetylspiramycin, kithromycin (column crystal leucomycin) and so on.
Lincomycin class commonly used varieties of lincomycin (japanamycin), clindamycin (chlorojapanamycin) and so on.
Other antibiotics mainly against bacteria commonly used varieties are norethindrone vancomycin, fosfomycin, polymyxin, colistin, rifampicin and so on.
Anti-fungal antibiotics commonly used varieties of amphotericin B, ashwagandha, gramicidin, mycobacteria, trichothecenes
Anti-tumor antibiotics commonly used varieties of mitomycin, adriamycin, epimedicin, actinomycin D and so on.
Antibiotics with immunosuppressive effects such as cyclosporine (cyclosporine, santiamine).
Rational use of antibiotics
In 1928, the British bacteriologist Fleming invented penicillin, which is a major milestone in the history of human medical science.
In the past 70 years, penicillin as the representative of antibiotics, from the hands of the disease to save tens of thousands of living beings, for human health has made a monumental achievement. Until today, antibiotics are still a powerful weapon against all kinds of germs.
In recent years, due to the over-reliance on and abuse of antibiotics, antibiotics in the treatment of disease at the same time, but also become a threat to human health "invisible killers" and caused serious concern in the community.......
Shocking resistance to bacteria
There are three major pathogenic microbial threats that will face mankind in the 21st century. Multidrug-resistant tuberculosis (MDR-TB), HIV, and drug-resistant strains of hospital-acquired infections, with drug-resistant bacteria developing at an alarming rate.
According to Zhang Yanxia, vice chairman of the All-Army Hospital Infection Committee and director of the infection control department at the 304th Hospital, in the 1920s, the main pathogen for hospital infections was streptococcus. In the 1990s, methicillin-resistant Staphylococcus aureus (MRSA), enterococci, penicillin-resistant Streptococcus pneumoniae, fungi and other drug-resistant bacteria. Quinolone antibiotics have been in China for only 20 years, but the resistance rate has reached 60% 70%.
The emergence of a large number of drug-resistant bacteria has led to more and more difficult-to-treat infections, more and more chances of infection with conditionally pathogenic bacteria, and higher and higher costs of treating infectious diseases. For example, penicillin-resistant Streptococcus pneumoniae, which used to be very sensitive to penicillin, erythromycin and sulfonamide, is now virtually invulnerable to penicillin, erythromycin and sulfonamide. Pseudomonas aeruginosa is 100% resistant to 8 kinds of antibiotics such as amoxicillin and cilicin, and Klebsiella pneumoniae is 51.85%-100% resistant to 16 kinds of high-grade antibiotics such as cilicin and fudaxin. Methicillin-resistant Staphylococcus aureus (MRSA) has no cure except vancomycin.
Director Zhang Yanxia said, multi-drug-resistant bacteria caused by infections pose a serious threat to human health, the abuse of antimicrobials has made human beings pay a painful price. 1950s in Europe and the United States first methicillin-resistant Staphylococcus aureus infections, this infection soon swept the globe, the formation of the world's pandemic, 50 million people were infected, deaths amounted to more than 500,000 people.
The battle between human beings and pathogenic bacteria has never stopped, and the pathogenic bacteria and the antibiotics that destroy them are a pair of eternal conflicts. From the history of bacterial resistance development can be seen, in a new antibiotic after the emergence of a number of drug-resistant strains of bacteria. It takes about 10 years for medical workers to develop a new antibiotic, while it takes only 2 years for a generation of drug-resistant bacteria to develop, so the development of antibiotics is far from being able to keep up with the reproduction of drug-resistant bacteria. Currently, many people with serious clinical infections die because of drug-resistant bacteria, and antibiotics are ineffective.
Many experts are worried that the misuse of antibiotics will mean the end of the antibiotic era. People can not help but worry that in the near future, there will be a kind of bacteria resistant to all antibiotics, that is to say, mankind will return to the last century before the 1920s without antibiotics, which will be a tragedy for mankind.
Who's to blame for the misuse of antibiotics
Wen Zhongguang, director of the respiratory department at the 304th Hospital, said that although the rational use of antibiotics can also produce drug-resistant bacteria, at least it can slow down the development of drug-resistant bacteria. In the United States, it is very easy to buy a gun, but it is very difficult to buy an antibiotic. Antibiotics are strictly controlled prescription drugs, doctors are penalized for prescribing them, and patients must have a prescription to buy antibiotics. In China, where antibiotics are readily available at pharmacies, their misuse is widespread.
According to the World Health Organization (WHO) in the international multi-center survey, hospitalized patients in the application of antibiotics accounted for about 30% of drugs, antibiotics accounted for 15-30% of the total expenditure on drugs. A hospital in China in 2000 on the use of antibiotics in the hospital inpatient survey, inpatient use of antibiotics accounted for 80.2%, of which the use of broad-spectrum antibiotics or combined use of more than two kinds of antibiotics accounted for 58%, greatly exceeding the international average level.
Director Wen believes that there are many reasons for the misuse of antibiotics in China:
One is the doctor's reason. Although every doctor has the right to prescribe antibiotics, not every doctor knows how to use them appropriately. Some doctors have a poor grasp of the indications for the use of antibiotics, do not pay attention to the pathogenicity of the clinical examination, and use antibiotics based on experience. Some of them do not understand the pharmacokinetic characteristics of various antibiotics and are not standardized in terms of dosage, route of administration and time interval. Individual doctors in the economic interests of the drive, contrary to professional ethics, to the patient to prescribe a lot of high-grade antibiotics do not need, not only increased the burden on the patient, but also more importantly to the patient's body caused new harm, accelerated the production of drug-resistant bacteria.
The second reason is the patient. Director Wen told this story. Once he went out to the specialist clinic received a patient with a common cold, director Wen gave her a checkup, prescribed about 20 yuan of medicine. The patient was very upset and asked for antibiotics and an infusion. Director Wen said that most colds are viral infections, and for people with normal immune function, antibiotics are not needed because they can kill germs but not viruses. Colds are self-limiting illnesses, and the antibodies produced by the body can neutralize the virus and cure it. But many people in China lack medical knowledge, little knowledge of the harm of antibiotic abuse, outpatient clinics often have patients named antibiotics, and the more expensive the better, the more high-grade the better, is also one of the reasons for the abuse of antibiotics.
Third, social reasons. In foreign countries, antibiotic drugs are not allowed to advertise. In China, drug manufacturers in order to pursue profits, in the mass media broadcast a large number of antibiotic advertisements, overstated, exaggerated its therapeutic effect, greatly misleading consumers, resulting in a lot of patients "follow the ads", the abuse of antibiotics played a role in promoting. At the beginning of this year, the State Drug Administration and the State Administration for Industry and Commerce jointly issued a "notice on strengthening the review and management of advertisements for prescription drugs", which strictly prohibits prescription drugs from being advertised in the mass media, especially "blocking" the overwhelming antibiotic advertisements, which is really beneficial to the country and the people.
Fourth is the reason of food. Individual places in the breeding industry abuse of antibiotics, chicken, duck and other feed mixed with antibiotics, some fish farmers in order to reduce the occurrence of fish disease, fish ponds built on the bottom of the pond spread a layer of quinolone antibiotics. On the one hand, the residual antibiotics in animals and poultry will be transferred to human beings, and on the other hand, the drug-resistant bacteria produced by animals and poultry will also be transmitted to human beings. Internationally, it is strictly prohibited to use the same antibiotics for humans and animals. After an animal develops resistance, its resistant plasmid can be quickly transmitted to humans through contact.
Reasonable use of antibiotics to get out of the misunderstanding
Almost all people have been exposed to antibiotics at one time or another, but few people really know how to use them properly. Many doctors, including a significant number of physicians, have many misconceptions about the use of antibiotics.
Myth one: antibiotics can prevent infection. A shopping mall in Beijing, a worker to do lumbar disc herniation surgery, in order to prevent infection, the doctor gave him a large dose of antibiotics, causing diarrhea. The doctor used antibiotics to stop the diarrhea, but the diarrhea became more and more severe, and his life was in danger. The expert consultation concluded that it was "antibiotic-associated colitis" caused by the misuse of antibiotics. Antibiotics were immediately stopped and ecological balance therapy was used, and the condition was quickly brought under control. According to the experts, antibiotics can only be used to treat infections caused by susceptible bacteria, but not to "prevent" them from occurring. The use of antibiotics to prevent infections is tantamount to giving bacteria a preventive shot and inducing bacterial resistance. Improper use of antibiotics can cause disruption of the body's flora and induce other diseases. All medical personnel should have a strong realization that the process of using antibiotics is the process of cultivating drug-resistant strains of bacteria, and that every time an antibiotic is used, a 10% resistance rate is generated. So, to prevent infections, the first step is to control the use of antibiotics.
Myth two: antibiotics can be used externally. Many surgeons often make antibiotics into a liquid to flush the wound, some in the postoperative to the wound to sprinkle antibiotic powder, many patients with rifampicin point eye ...... This is very incorrect. Antibiotic textbooks make it very clear that all biosynthetic antibiotics, salbutamol antibiotics, and antibiotics used to treat severe infections are not to be used externally. Rifampicin is the drug of choice for the treatment of tuberculosis, and the use of rifampicin is very strictly controlled abroad, forbidden to be used externally, or the doctor will be disqualified. In China, many doctors use rifampicin for patients' eyes. Due to the widespread use of rifampicin, resistance to the drug has increased significantly. According to a survey by the World Health Organization, China's tuberculosis drug resistance rate is as high as 46%, the number of tuberculosis cases is the second highest in the world, and one-third of the population is infected with tuberculosis, with more than 400 million people infected. Although there are many reasons for this, it cannot be said to be unrelated to the abuse of rifampicin.
Myth No. 3: Broad-spectrum antibiotics are more effective than narrow-spectrum antibiotics. All patients want to get rid of the disease, especially the antibiotics have high expectations of the efficacy. Experts believe that anti-infection treatment is a gradual process, for acute infections, antibiotics are generally used for 3-5 days. There are many patients who are eager for success, and when they feel no obvious improvement in their symptoms after one day of use, they mistakenly think that it is ineffective and ask their doctors to use other antibiotics or increase the use of other antibiotics. In outpatient clinics and clinics, we often see the phenomenon of using several kinds of antibiotics for a common cold, which not only increases the burden of patients, but also increases the resistance of bacteria, resulting in secondary infections. The principle of antibiotic use is to use narrow-spectrum instead of broad-spectrum, to use low-level instead of high-level, and to use one to solve the problem instead of two. Only severe infections with unknown pathogens, simultaneous infection with two or more pathogens, or bacterial resistance to antibiotics should be used in combination, while mild or moderate infections should not be treated with antibiotics in combination.
Myth 4: Newer antibiotics are better than older ones. Many people like to follow the advertisements to use drugs, that antibiotics "the newer the better", "the more expensive the better", "the more advanced the better". It is not uncommon to see patients come to the hospital and ask for the advertised drugs or the expensive ones by name. In fact, each antibiotic has its own characteristics, advantages and disadvantages of different, generally according to the disease, according to the person to choose, adhere to the individualization of the drug. For example, erythromycin is an old antibiotic, very cheap, it is quite good for legionella and mycoplasma infections of pneumonia, while the very expensive carbapenem antibiotics and third-generation cephalosporins are not very effective for these diseases. Generally speaking, a new antimicrobial agent is developed, and it is advanced, but it does not necessarily mean that all new drugs are better than the old ones. The key is the right medicine for the patient. Some old drugs are more stable and cheaper, so people may be more sensitive if they don't use them regularly. Patients should not be misled by advertisements.
Myth No. 5: Antibiotics are anti-inflammatory drugs. Most people equate antibiotics with anti-inflammatory drugs and mistakenly believe that antibiotics can treat all inflammatory diseases. In fact, antibiotics are only suitable for inflammation caused by bacteria, but not for inflammation caused by viruses, such as viral colds or asthma patients with allergic inflammation. If antibiotics are also used to treat sterile inflammation caused by non-pathogenic bacteria, they can be harmful rather than helpful. A young girl with a cold, throat inflammation, the local hospital with antibiotics, not only did not get better, but the body temperature rose to 40 ℃, fuzzy consciousness, covered with a rash, rushed to the 304 hospital rescue. The doctor diagnosed drug fever caused by the abuse of antibiotics. He was given glucose and recovered quickly. A patient with bronchial asthma was given a high dose of broad-spectrum antibiotics at a hospital, which caused a trichinella infection in his lungs. Sent to 304 hospitals, the doctor gave him to stop using broad-spectrum antibiotics, and targeted use of antifungal drugs, and soon recovered. Experts said that there are a large number of normal beneficial flora in the human body, these flora have the role of mutual control, so as to maintain the micro-ecological balance of the body, in order to prevent a certain kind of bacterial reproduction and overgrowth and the occurrence of disease. If you use antibiotics to treat aseptic inflammation, these drugs into the body will not distinguish between the enemy and us, killing innocent people, but suppressed and killed the beneficial flora in the body, causing dysbiosis, resulting in decreased resistance, leading to the occurrence of other diseases. In addition, the use of antibiotics is not recommended for the treatment of local soft tissue bruising, redness, swelling, pain, contact dermatitis caused by allergic reactions, dermatitis caused by medications, and inflammation caused by viruses.
Out of the loop, a different way of thinking about anti-infection
In recent years, developed countries have put the prevention of infections to improve the patient's immunity, because the vast majority of nosocomial infections are endogenous, and the patient's immunity has a close relationship. The human body has
6 major reservoirs of bacteria: upper respiratory tract, oral cavity, gastrointestinal tract, urinary tract, vagina, and skin. If their biosociety is out of control, there is a constant supply to areas of infection or dysbiosis. Pathogenic bacteria can be inexhaustible, and even if all the bacteria in a reservoir are killed, they are immediately colonized by other bacteria. This is the case with hospital-acquired infections, where sensitive strains of bacteria brought in when a patient is first hospitalized are killed off after hospitalization and replaced by drug-resistant strains of bacteria from hospital staff or other patients. In China, traditional Chinese medicine emphasizes the importance of "eliminating the evil and supporting the positive", and the two should not be neglected. Antimicrobials are mainly used to eliminate evil, but antibiotics must work through the body's own immunity. Therefore, there should be other measures to support the positive, two-pronged approach, in order to achieve the best results.
For a long time, we have been caught in a vicious circle of "infections, antibiotics, drug-resistant strains, new infections, and antibiotics. If we can improve the human body's immunity to reduce the population's chance of infection, we will get out of this circle. In the early 1990s, Professor Xiong Dexin, vice chairman of the microecology branch of the Chinese Association of Preventive Medicine, put forward the idea of "microecological therapy to prevent and treat diseases. The difference between antibiotics and microbial therapy is that antibiotics are used to treat diseases by inhibiting and killing disease-causing microorganisms. But micro-ecological therapy is through the support of physiological microorganisms, adjust and improve the internal environment of the human micro-ecosystem, promote micro-ecological balance, improve the body's level of immunity and planting resistance to disease prevention and treatment effects. It has been predicted that
The 20th century was the glorious period of antibiotics, and the 21st century will be the golden age of micro-ecological therapy.
Quantitative relationship between antibiotics and pathogen resistance
For a long time, people's understanding of pathogen resistance basically remains on the resistance mechanism of specific pathogens to specific antibiotics and the inhibition of specific antibiotics on pathogens. However, relevant studies have shown that there exists a macroscopic quantitative relationship between the use of antibiotics and the level of resistance of pathogenic bacteria, that is, a certain range of antibiotic use can lead to changes in the overall level of resistance of pathogenic bacteria and the rate of infection of resistant bacteria, and this relationship is the quantitative relationship between antibiotics and pathogenic bacteria.
The quantitative relationship between antibiotics and pathogenic bacteria has not been studied for a long time, and it is only in recent years that focused, in-depth studies have been carried out. In developed countries, especially in the Nordic countries, where the use of antibiotics is strictly controlled, more research has been carried out, while in developing countries, there is a gap in this field. There are two main factors contributing to the late start and uneven development of research in this field. First, research requires the collection and processing of data on a wide range of pathogens and antibiotic use through large-scale surveys. In developed countries, the monitoring organizations of pathogen resistance and antibiotic use are well established and can easily obtain and process a large amount of relevant data. In addition, the multidisciplinary collaboration of epidemiology, statistics, pharmacology, microbiology, and clinical medicine allows in-depth, detailed, and timely study of the quantitative relationship between antibiotic use and pathogen resistance.
In developing countries, the relevant monitoring organizations are not sound. In China, for example, data on pathogenic bacterial resistance and antibiotic use at all levels of medical institutions are managed by different functional departments and divisions, and information exchange is difficult, resulting in our research in this field lagging far behind that of developed countries.
Secondly, different antibiotic dosage units and commonly used dosages vary greatly and cannot be compared and superimposed in large-scale studies. Early studies were limited to the utilization of antibiotics and the cost of antibiotics, which did not accurately reflect the actual use of antibiotics. In order to solve this problem, the common daily dose for adults was used as the standard dose, and the consumption of different antibiotics was converted to a standardized unit, which was named as the daily dose (defined
doses, DDD), and the consumption of antibiotics was expressed in terms of the number of DDDs used. Each antibiotic consumption converted to DDD can be compared and superimposed. This method was recommended by the WHO in 1996 for the study and monitoring of antibiotic use. It was after the establishment of this standard that a great deal of progress was made in a short period of time. Studies in this area fall into three broad categories:
1, Large-scale studies of community-based populations
These studies are often conducted in a single region, country, or even on a very large scale in multiple countries. The results of these studies are important for guiding the development and revision of national and regional regulations to control the use of antibiotics, and for testing the effectiveness of control measures. Comparative studies in different countries can also be used to examine the effects of natural conditions, environmental factors, social factors, and level of economic development on the quantitative relationship between antibiotic use and the level of resistance of pathogenic bacteria.
Sweden set up a specialized agency in 1994, took the lead in launching a national systematic project STRAMA for antibiotic use and pathogen resistance, and took targeted measures to eliminate the irrational use of antibiotics, and after a number of years, the consumption of antibiotics in Sweden has been reduced by 22%, and the level of pathogen resistance has also been significantly reduced.
2,Small-scale studies in medical institutions
These studies focused on the quantitative relationship between the use of antibiotics and the resistance of pathogenic bacteria under different conditions in different hospitals, hospital districts, and different underlying diseases, and found and confirmed that there is a close relationship between the consumption of various antibiotics and the infection and resistance rates of common pathogenic bacteria.
The focus of these studies is usually on the most common and threatening pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, Pneumococcus, and Enterococcus, as well as on the most important antibiotics, such as vancomycin, macrolide antibiotics, and third-generation cephalosporins. The results of this study will be of great practical value in guiding clinical anti-infective therapy and controlling the increase in the level of drug resistance of pathogenic bacteria.
A study using multiple regression to analyze data on antibiotic use and pathogen resistance in six internal medicine wards of an Israeli hospital showed that consumption of amikacin and third-generation cephalosporins in these wards was strongly associated with the rate of clinically resistant bacterial infections.
There are only a handful of studies that have been done to reduce the level of resistance in pathogenic bacteria and the rate of infection by resistant bacteria by modifying the use of clinical antibiotics, which can be considered as the cutting edge of the research in this field, and the hope and ultimate goal of the explorers in this field.
Landman et al. successfully reduced methicillin-resistant Staphylococcus aureus (MRSA) and ceftazidime-resistant Klebsiella pneumoniae (KP) infections by decreasing the use of cephalosporins, imipenem, clindamycin, and vancomycin in hospitals, and by increasing the use of β-lactamase-inhibiting antibiotics.
Recent studies have also found that increased clinical use of ampicillin/sulbactam significantly reduces the level of resistance in Staphylococcus chimericus and Enterobacter cloacae, while increased use of cefepime reduces the rate of MRSA infection.
The authors have statistically analyzed the data related to antibiotic use and pathogen resistance in the burn ward of their hospital, and found that the use of antibiotics containing β-lactamase inhibitors was negatively correlated with the level of resistance of Staphylococcus aureus. In addition, we have accumulated all the data on clinical antibiotic use and pathogenic bacteria resistance in the burns ward of our hospital over the past 8 years, and have built a convenient database, which lays the foundation for further in-depth research.
In conclusion, the study of the quantitative relationship between antibiotic use and the structure and resistance level of pathogenic bacteria is of great significance in guiding the clinical anti-infective treatment, rationalizing the use of antibiotics, as well as formulating the relevant regulations to control the use of antibiotics, but at present, there are many aspects to be further explored in this field. At present, there are many barriers to the exchange of information about antibiotics and pathogenic bacteria in China, which requires the efforts of healthcare administrators, relevant experts and clinicians*** to strengthen the exchange of information, and to provide information of practical value for guiding clinical anti-infective treatment and reducing the level of pathogenic bacterial resistance through the in-depth study of the quantitative relationship between the use of antibiotics and pathogenic bacterial drug resistance.