Since the 1940s, antibiotics have created an indelible contribution to the health of humans and animals. Antibiotics can prevent infectious diseases, promote animal growth, and improve feed utilization. With the widespread use of antibiotics in livestock and poultry farming, adverse effects such as bacterial resistance and allergic reactions caused by drug residues are becoming more and more serious. Due to the political factors of governments, the scientific assessment system is different, resulting in controversy over the relevant policies on the use of antibiotics in feed. So far, there are still large differences in the use of antibiotics in different countries and regions. There is no unified understanding of how to use antibiotics reasonably. This article will review internationally important scientific reports on the resistance of feed antibiotics, as well as policies related to the use of antibiotics for feeding, and analyze and discuss the disputes arising from these policies. It is hoped that this issue will have a scientific and comprehensive understanding of the problem.
1 antibiotic growth promoter use policy
1.1 European
In the 1960s, there was a prevalence of enteritis caused by multi-drug-resistant Salmonella transmitted from dairy herds to the population in the United Kingdom. Hundreds of people were infected and 5 died. This public health incident prompted the British government to establish the Joint Commission on Antibiotic Use in the Livestock and Veterinary Industries, which published the famous Swann Report in 1969. The report pointed out that the side effects of antibiotics can cause harm to the human body, and the resistant bacteria produced by the animal body may be transferred to the human body. The report recommends that antibiotics used in animal farming should be differentiated between medical and forage; humans should be prohibited from using antibiotics in animal feed and that 10 criteria can be used as veterinary antibiotics for low doses in feed.
Since the 1980s, European countries have gradually introduced various policies prohibiting the use of antibiotic growth-promoting agents, but these policies have both political and scientific factors. In 1986, Sweden completely banned the use of antibiotic growth promoters in livestock feed without any scientific assessment. When Sweden was invited to join the European Union in 1996, Sweden adopted the “drug law†implemented in the country as one of the negotiating conditions. After years of negotiations, the EU finally agreed to the Swedish requirements and started to be a member of the European Union in 1999. The country began to implement gradually. On the other hand, many countries in the European Union have scientifically assessed different antibiotics and made relevant regulations according to the characteristics of different antibiotics and their importance in medicine. For example, in 1995, Denmark banned the use of the glycopeptide antibiotic avomycin in feed, due to the production of anti-glycopeptide enterococci and its possible public health problems. In January 1998, Denmark banned the use of virginiamycin as a growth promoter because its analogous compound is an effective drug for the treatment of vancomycin. Since January 2000, Danish antibiotics have been limited to prescription treatment of animal diseases in order to reduce the amount of antibiotics used in the livestock industry.
In 1997, the European Commission banned the use of avomycin as a feed additive in all member states. Avomycin is a similar substance to vancomycin. Excessive use of avomycin may produce more vancomycin-resistant strains. It should be noted that Avomycin has never been approved as a feed additive in the United States. . In 1999, the European Commission reported that the Scientific Steering Committee's Opinion on Antibiotic Resistance stated that timely action must be taken to reduce the overall use of antibiotics, suggesting that antibiotics must be used with caution. Since July 1999, the EU has banned the use of bacitracin, spiramycin, virginiamycin and tylosin in feeds. In September 2003, the European Union issued the European Parliament and Council Regulation (EC) No 1831/2003. By 2006, all antibiotic growth promoters, including ionophore antibiotics, will be discontinued in EU member states. Currently, the use of antibiotics and chemical feed additives is subject to approval under the EU Council Regulation 70/524/EEC and its amendments.
1.2 US
The US Food and Drug Administration (FDA) has been managing and controlling antibiotic growth promoters on scientific principles. In the 1970s, when the FDA discovered that individual approved antibiotics for feeding had the potential to cause public health consequences, in 1977, the FDA proposed to withdraw the proposal to allow penicillin and tetracycline to be added at low doses in animal feed, but Since the results of subsequent studies show that the transfer of resistant bacteria from animals to humans is rare, the increase in human bacterial resistance is the result of human antibiotics, so this recommendation has not been implemented. In 1980, the National Academy of Sciences reported that the effect of low-dose antibiotics in animal feed on human health stated that the lack of data on the relationship between human health and the use of low-dose antibiotics did not equate to the absence of the hazard. In 1984, Seattle-Jin County Health Department's research report "Monitoring of the prevalence of Salmonella and Campylobacter in animal populations" found that Campylobacter did indeed flow to humans through the consumption of poultry products. In 1987, the FDA asked the American Medical Institute (IOM) to evaluate human health risks associated with the addition of penicillin and tetracycline to animal feed. The following year, the IOM report “Human Health Risks from the Use of Low-Dose Penicillin or Tetracycline in Animal Feeds†stated that no direct evidence was found to prove that the use of these two antibiotics endangered human health, but found a large amount of circumstantial evidence.
Since the 1990s, the United States has gradually affirmed the risk of bacterial resistance caused by antibiotics in food animals and the potential harm to human health. In 1998, the Federal Register (FR) issued a draft guide to the “Evaluation of the Effects of Microbial Effects of Antibacterial New Veterinary Drugs on Food and Human Health on Human Healthâ€, and in the following year, it was proposed to evaluate the microbiological safety effects of veterinary antibacterial new drugs on humans and ensure antibacterial The Safety Framework for New Drugs in Food Animals states that government agencies are beginning to consider issues related to the use of new veterinary antibacterial drugs for food animals and how to evaluate and reduce the potential impact of animal antibacterials on human health. In 1999, the National Research Council (NRC) evaluated the benefits and risks of using antibiotics in food animals in the report Pros and Cons of Using Antibiotics in Food Animals. It is recommended to establish a national database for the approval of veterinary antibiotics. Support for scientific procedures and policy development. In the same year, the FDA-CVM released the Industry Guide (GFI), "The consideration of the microbiological effects of new anti-bacterial drugs for veterinary animals on human health," pointing out that antibacterial drugs used in food animals can alter the intestinal flora of animals, including increased pathogens. The amount of load, the emergence of drug resistance, consumption of animal food contaminated by bacteria will endanger human health. However, the US Government Accountability Office (GAO) report “Food Safety: The Use of Antibiotics in Agricultural Production and Its Impact on Human Health†states that there is currently no comprehensive assessment of the specific extent of disease-causing disease and death caused by drug-resistant bacteria. . In 2004, GAO's research report "Antibiotic resistance: federal agencies should better focus on addressing the health risks of animal antibiotics to humans" pointed out that antibiotic-resistant bacteria have been transferred from animals to humans, but researchers are There is a divergence in the extent to which such transfers affect human health. The Department of Health and Human Services (HHS) reviewed the report and listed 11 other complementary studies not cited in the GAO report, which confirmed the use of antibiotics in food-producing animals and antibiotic resistance in humans. There is a link between the resulting damage to human health. In 2003, the FDA issued an industry guide, “Safety Assessment of the Microbiological Effects of Antibiotic New Veterinary Drugs on Human Pathogenic Bacteria,†which provides a risk-based assessment for assessing drug resistance associated with the use of antibiotic veterinary drugs in food animals. method. In 2009, the American Society for Microbiology published a report on Antibiotic Resistance: An Ecological Perspective on an Old Problem, emphasizing that antibiotic resistance is a natural phenomenon that cannot be eliminated. The reality is to classify antibiotic drugs scientifically. The variety of drugs that have a major impact on human health is not used in large quantities in livestock production, so the need to use antibiotics cautiously and responsibly and eliminate unnecessary use is an urgent problem to be solved.
The United States has also introduced a series of policies on the possible harm caused by feed antibiotics. On January 4, 2012, the FDA issued a decree prohibiting the use of important medical drug cephalosporins in cattle, pigs, chickens and turkeys, but veterinarians can still use cephalosporins in ducks and rabbits. The new decree issued this time is similar to the cephalosporin antibiotics promulgated in 2008 that prohibit the use of "special labels" on food animals, except that the 2008 law was finally revoked. Subsequently, the US FDA issued an industry guide "Prudently use human antibiotics in food animals", arguing that it is not prudent to use human antibiotics as important animal growth promoters, and propose that if necessary, they should be limited to those It is considered to be a very necessary use for animal health and needs to be used under veterinary supervision and consultation. In 2013, the FDA issued an industry guide requiring pharmaceutical companies to voluntarily change the use of antibiotics to promote animal growth, indicating the pharmacological effects of these antibiotics. The new regulation between the "prescription drugs" (Rx) and "over-the-counter drugs" (OTC), a new category called "Veterinary Guidance Drugs" (VDF), the new measures may make the United States veterinary drug management more scientific.
In general, unlike the EU's total ban on antibiotic growth promoters, the US FDA believes that it is important to use antibiotics cautiously to control antibiotic resistance. Whether Europe's veterinary drug policy can succeed, ultimately depends on whether it can reduce the use of antibiotics in animal husbandry, whether it can reduce the harm of drug-resistant pathogens to human health, whether it is to the overall economy and the human environment. Protection and other aspects have played a positive role.
1.3 Regulations for the use of feed antibiotics in other countries and regions
Most countries other than the EU still allow a small number of safer antibiotics to be used as feed additives, rather than being indiscriminate. In the feed regulations of Japan, Brazil, Russia and other countries, some safer antibiotics (such as zinc bacitracin, colistin sulfate, etc.) are allowed to be added in low doses in the feed, and they are usually prescribed for use, such as Russian requirements. Animals must have a three-week drug holiday before slaughter. China currently classifies antibiotics that can be used in animal husbandry as low doses in feed (Appendix No. 168) and can only be used for therapeutic purposes (Appendix II). In Appendix I, only 10 kinds of antibiotics such as oxytetracycline, colistin and bacitracin were approved as feed drugs. In order to ensure the safety of veterinary drugs, China has also established standards for the quality and safety of veterinary drugs including the following regulations: “Regulations on the withdrawal period of some varieties of national standards and professional standards for veterinary drugs†(Announcement No. 278 of the Ministry of Agriculture) List of Veterinary Drugs and Other Compounds (Announcement No. 193 of the Ministry of Agriculture) Catalogue of Drugs Prohibited in Feed and Animal Drinking Water (Announcement No. 176 of the Ministry of Agriculture) "Maximum Residue Limits of Veterinary Drugs in Animal Foods" (No. 235, Ministry of Agriculture) Announcement) and so on. In general, countries and regions recognize that there may be risks in the use of antibiotics, but the measures taken to reduce this risk are different.
1.4 International organization on the risk assessment of food-borne antibiotic resistance
The use of antibacterial drugs in the production of food animals is an important risk factor for the generation and transmission of drug-resistant bacteria and drug resistance determinants. The spread of food consumption to humans will cause problems such as the decline and ineffectiveness of human antibacterial therapy. To this end, international organizations such as the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAD), the World Organisation for Animal Health (OIE), and the International Codex Alimentarius Commission (CAC) have held meetings to conduct food-borne antimicrobial resistance. Risk assessment (Table 1).
1.5 Human medicine and veterinarians on important anti-microbial drugs
In 2007, the WHO Expert Committee issued a report in Copenhagen, Denmark, according to the standard (1) that the antimicrobial drug is the only or a few alternative drugs for the treatment of serious human infectious diseases and (2) for treatment can be Antimicrobial agents that transmit diseases caused by pathogens in non-human environments (these non-human commensal bacteria can transmit drug resistance factors to human bacteria), and classify important medical antibacterial drugs into C categories ( Critically Important), Highly Important, and I. Class C needs to meet both standards 1 and 2, Class H meets Standard 1 or 2, Class I does not meet Standard 1 or meets Standard 2. In 2011, WHO conducted a second major medical anti-microbial drug category. Second and third revisions (Table 2).
In 2007, the OIE listed a list of important antibiotics for veterinarians and updated them in 2012 (Table 3). According to the standard (1) questionnaire, more than 50% of the questionnaires consider the compound to be an important veterinary antibacterial agent and (2) the compound is used to treat serious animal disease types and there is no corresponding alternative treatment for the disease. Veterinary Critical Antibiotics are classified into Veterinary Critically Important Antimicrobial Agents, Veterinary Highly Important Antimicrobial Agents, and Veterinary Important Antimicrobial Agents. Among them, the VCIA class satisfies the standards 1 and 2 at the same time, the VHIA class satisfies the standard 1 or 2, and the VIA class does not satisfy the standard 1 or 2.
OIE's important anti-microbial drugs developed by OIE do not include anti-microbial drugs that are only used in human medicine to protect the effectiveness of human anti-microbial drugs. In the VCIA category, fluoroquinolones and third- and fourth-generation cephalosporins are important antibiotics for humans and animals. The use of these two classes of antibiotics should follow the following principles: (1) When the animal does not have clinical symptoms, it is not Use of feed and drinking water as a preventive drug; (2) If it is not necessary, it should not be used as a first-line treatment. When used as a second-line treatment, it should be used according to the results of bacteriology; (3) Minimize the use of drugs outside the label. It is subject to the laws and regulations of each country. 　　
Author: Cheng Gu Yue, HAO Hai Hung, Xieshu Yu, a dream to wear red, Huang Lingli, Wang Xu, Liuzhen Li, Yuan Zonghui
National Veterinary Drug Residue Reference Laboratory of Huazhong Agricultural University, Key Laboratory of Food and Veterinary Drug Residue Testing of the Ministry of Agriculture,
Ministry of Agriculture Livestock and Poultry Product Quality and Safety Risk Assessment Laboratory (Wuhan)
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