Release date: 2015-01-14
At the beginning of the last century, one third of the world’s people died of pneumonia, tuberculosis, enteritis and diarrhea. Today, heart disease and cancer are the main killers of humans, with fewer than 4.5% due to pneumonia and flu deaths. This is an important achievement in the field of public health for human application of antibiotics [1]. Now humans have come to the other extreme: the abuse of antibiotics has led to the emergence and widespread spread of resistant bacteria.
A world-scale metagenomic study shows that microorganisms containing resistance genes are ubiquitous in nature [2]. This means that mankind is about to return to the era of no antibiotics. A large part of the medical system may return to a hundred years ago, and mild bacterial infections may have fatal consequences. On World Health Day 2011, the World Health Organization put forward the slogan “Resistance to Drug Resistance – No action today, no medicine available tomorrowâ€, calling for the suppression of drug resistance transmission [3], and announced in April 2014 The first global antibiotic resistance report based on data from 114 countries around the world [4]. The United States also believes that antibiotic resistance is a major public health challenge in 2014.
What is antibiotic resistance?
People in daily life will hear a lot of "drug tolerance", some tolerances occur in people - for example, diabetes patients repeatedly use insulin, its efficiency will be reduced; chronic pain patients repeatedly use painkillers, the effect will be worse and worse.
However, the resistance of antibiotics is different. It is not that the human body is resistant to antibiotics, but that the pathogens in the human body are tolerant; and the pathogens will spread. This is why drug resistance is a global problem, even if you do not eat antibiotics will have a relationship with you.
By definition, resistance means that “microorganisms such as bacteria, viruses, fungi, and parasites change, making the original targeted treatments ineffective [5].†After the pathogens develop resistance, antibiotics cannot be in the body. Identify or attack the germ. Assuming that drug-resistant pathogens are transmitted worldwide, all patients infected with such bacteria cannot use traditional treatments to control the disease. In layman's terms, the resistance of antibiotics actually produces a new type of antibiotic-resistant pathogen in the body, and the emergence of this new organism can pose a threat to the health of all human beings.
How terrible is resistance?
Once a few dozen units of penicillin can save lives, and now millions of units may not produce any effect. In the heyday of antibiotics in the 1960s, about 7 million people worldwide died of infectious diseases each year, and this number has risen to 20 million in this century [6]. Even if the individual does not abuse the antibiotic, it may be infected with the resistant bacteria cultivated by the abuse of antibiotics.
In 2012, there were about 450,000 new cases of MDR-TB. Currently, extensively drug-resistant tuberculosis has appeared in 92 countries and regions. These patients with drug-resistant strains have to face longer courses and poorer. Therapeutic effect [7]. The widespread drug-resistant tuberculosis, artemisinin-resistant malaria and gonorrhea resistant to third-generation cephalosporins, such as the plague spread around the world, means that the diseases we have overcome may once again become incurable diseases for all humanity. . The germs we will face in the future will be an enhanced version a hundred years ago, and it is urgent to develop new drugs based on new targets. After all, the development of new drugs is a voluminous project, and it is difficult to catch up with the speed of bacterial mutation. If the drug-resistant bacteria cannot be controlled, this will no longer be a problem of personal treatment costs, but the economic burden of the entire society.
Why is there antibiotic resistance?
To understand drug resistance, we must start with the "antibacterial" mechanism of antibiotics. For example, the three-plate axe of the bite gold, antibiotics against bacteria is nothing more than a few tricks: 1) inhibit cell wall synthesis; 2) inhibit protein synthesis; 3) inhibit DNA synthesis; 4) infection bacteria growth and reproduction.
The ancestors of bacteria can be traced back to 3 billion years ago, and they have a very strong adaptability to the environment, which is mainly due to the continuous evolution of hundreds of millions of years. The evolution of resistant strains is a natural phenomenon of survival of the fittest. With the advent of antibiotics, drug-sensitive strains have been killed. However, as the microorganisms proliferate from generation to generation, accidental genetic mismatches can form a small number of mutant strains that are insensitive to the drug. Genetic mismatches are things that happen naturally in nature. Just in this second, there may be a mutant cell in E. coli in your intestines. But to make a "accidental mistake" meaningful, and can be very influential, you need a strong fertility. Of course, it is not too difficult for a simple creature like bacteria.
Where are these bacteria lucky people who are considered by the ancestors to be "sweet and cracked dates"? Some have changed the target of antibiotics and their effects, so that antibiotics can't touch the way; others are covered with iron. Cloth, so that antibiotics can not enter the bacteria; and some active attack to produce inactivated enzymes, inactivate antibiotics. In general, they all made structural changes through their own initiative, and let the "stupid" antibiotics fail.
The types of antibiotics and combat modes are limited, and bacteria can be used to avoid attacks. In this way, the netted fish that can't be hit by antibiotics can grow up with their tenacious viability. They can not only breed themselves, but also transmit "resistance" to other bacteria through genes.
Antibiotic abuse is the biggest driver of drug resistance
Mutations are the root cause of drug-resistant bacteria, but without the abuse of antibiotics, resistance does not spread at such a rapid rate.
Mutations are accidental events. Most of the mutations have no effect. Most of the remaining mutations are harmful. Only a few of them are harmful and can also be accompanied by weak drug resistance. The harmless mutations are almost insignificant. . It is almost impossible for a mutation to obtain perfect resistance to bacteria; in reality, almost all drug resistance is gradually accumulating mutations and gradually increasing.
Before the large-scale antibiotic treatment, the drug resistance effect has little meaning to the bacteria, and the harmful effect of the mutation itself is more important, so the drug resistance is basically impossible to spread. Normal use of antibiotics can kill almost all of the target bacteria, and individual fish that are leaking nets are often destroyed by the body's immune system. Some of these bacterial individuals, although already bearing drug-resistant sprouts, are not sufficient to withstand normal doses of antibiotics and will disappear as individuals die. Therefore, resistance can be very slow even if it can spread.
However, if the body is infected, failure to use a large dose of antibiotics to kill the bacteria completely, will make these less sensitive sprouts survive to establish a new population; the new population will continue to mutate on this basis. Insufficient doses, no treatment, and frequent replacements, these factors will greatly reduce the bactericidal effect, turn acute infections into chronic infections, prolong the unhealed, give drug-resistant bacteria a chance.
The danger of the abuse of antibiotics is not only to promote drug resistance. Unreasonable use of antibiotics can cause liver and kidney damage, affecting children's teeth and bone development. In addition, the long-term use of certain antibiotics may also break the balance of the flora in the body, causing a large number of bacteria to multiply under unrestricted conditions, resulting in a double infection. According to follow-up studies, long-term consumption of antibiotics can reduce human immunity and increase the risk of cancer [12].
Nosocomial infection is a breeding ground for drug-resistant bacteria
Because most of the inpatients in the hospital are seriously ill and have more infections, the hospital has become a hotbed of cross-infection of drug-resistant bacteria. According to 2013 data, the number of drug-resistant infections in various hospitals in the United States has doubled 2-4 times compared with 2008 [8]. A diehard molecule with "multiple drug resistance" is known as the "superbug". Traditional super bacteria include methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The recently discovered New Delhi metalloproteinase-1 (NDM-1)-resistant bacteria are "pan-resistant", leaving most antibiotics at a loss. The European Society for Clinical Microbiology and Infectious Diseases predicts that once infected with such bacteria, there is no cure for at least 10 years [9].
Although they are called "super", they do not have any super powers in terms of virulence, and they are still the same symptoms of infection, but there is no way for any antibiotic to take it. Once infected with "super bacteria," patients can develop severe inflammatory reactions and even die. Because there is no cure, doctors can't do anything about it. At present, such "superbugs" that are not in danger are spreading worldwide. Three strains of NDM-1 positive strains have been detected in the Chinese CDC and the Chinese Academy of Military Medical Sciences laboratory in 2010 when testing previously preserved strains [10].
Antibiotic application in agriculture is also worthy of attention
Compared with the amount of antibiotics used in agricultural products, the amount of antibiotics used in humans is dwarfed. More than 90% of the world's antibiotics are used as feed additives in food animals. According to the US Centers for Disease Control and Prevention, 73% of the antibiotics sold in the US market in 2013 were purchased by veterinarians [13]. China's animal husbandry antibiotic consumption in 2010 was 97,000 tons, accounting for 46.1% of the total annual output. The large use of penicillin, tetracycline and chlortetracycline in the livestock industry is mainly to increase livestock production, not to treat diseases.
The US FDA had wanted to ban the addition of antibiotics as early as the 1970s, but it was forced by domestic animal husbandry pressure. Now the ban is put forward by the FDA. Studies have shown that the resistance rates of tetracycline and erythromycin in farm cattle in the United States are 42.9% and 12.7%, respectively, due to the large amount of antibiotics added to the feed, which is much higher than that of the American bison (8% and 4% respectively, although the data is also Exceeded the researchers' expectations) [14].
Antibiotics are naturally present in soil and water. As agriculture changes to the environment, the bacteria obtained in the soil are highly resistant, whether or not directly irrigated with wastewater. It suggests that bacterial resistance has spread, and the use of antibiotics should not be underestimated. Inadvertently taking low-dose long-term intake of antibiotics can accelerate the development of pathogen resistance. Cases that are not sensitive to ciprofloxacin have been reported abroad, and it is speculated that ciprofloxacin is added to chicken feed to cause food residues [15]. Antibiotic residues in foods (such as farmed fish) can also cause allergy symptoms.
Antibiotic allergy is also ubiquitous, but it is not the same as drug resistance.
According to the national drug adverse reaction monitoring report issued by the State Food and Drug Administration, there were a total of 1.317 million adverse drug reaction events/reports in 2013, of which 39.3% were caused by anti-infective drugs [11]; one of the important reasons is that we A well-known antibiotic is allergic.
Although both are negative effects of antibiotics, resistance and allergy are two different things. The former is the grievance between bacteria and drugs, while the latter is the entanglement between drugs and individuals. Almost all antibiotics can cause allergic reactions, but penicillins and cephalosporins are the most common. Taking penicillin allergy as an example, penicillin thiazoles can be produced during the production and storage of penicillin or during metabolism in the body. These substances can synthesize penicillin thiazole protein in the human body, stimulating the body to produce an immune response, which is an allergy symptom. When you are young, you need to do a "skin test" for penicillin needles, just to check for allergies.
Penicillin allergy varies from person to person, but it is very common, with an average of ten people. Specific manifestations include rash, fever, angioedema, and anaphylactic shock in severe cases. The mechanism of action of allergies is related to the antibiotic component itself, and oral antibiotics can also cause allergies. However, due to the first-pass effect of oral preparations, the absorption and utilization in the body is much lower than that of intravenous injection, and the allergic symptoms are mild. At present, oral antibiotics are generally not used in clinical trials. If the patient has no history of allergies, they can be taken directly.
Although in theory, the intake of environmental antibiotics may cause allergic reactions, but the dose of antibiotics in nature is very small, almost enough to cause allergic reactions, the public does not need to worry about this. However, there are cases in this case. For example, a recent case of severe allergic symptoms caused by eating blueberry pie in the United States is caused by streptomycin contained in blueberries, but it is worth noting that the case itself has a history of asthma. Therefore, it is really prudent for people with previous allergic diseases [16].
What should be done if there is a proliferation of drug resistance?
Kelly Clarkson, the American music singer, sang in her popular hit "Stronger": "What doesn't kill you makes you stronger..." Those who failed to knock down your opponent and made you Stronger. The same is true for bacterial resistance. In the "post-antibiotic era", how do we deal with the grim situation of the spread of drug-resistant bacteria?
First, publicity of the rational use of antibiotics should be carried out at all levels of society. Individuals and doctors should use antibiotics reasonably to achieve "precautions" and strictly control usage, dosage and course of treatment. Rapid clinical bacterial testing should be developed during clinical use to obtain bacterial resistance information as early as possible to avoid blind medication. Multi-drug combination can be used during treatment to reduce the possibility of drug resistance. The hospital should organize infectious disease disciplines and related experts, strengthen supervision of the use of antibiotics in the hospital and conduct regular training for relevant departments. In addition, because the speed of emergence of drug-resistant bacteria is much higher than the speed of research and development of new antibacterial drugs, some companies with research and development capabilities will turn their attention to drugs for the treatment of chronic diseases for profit, and thus enter a vicious circle. Therefore, the government should encourage and support the development of new antibiotic drugs.
Source: Shell Network
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