The drinking water standard has since been changed to 50 mg/L, but the STLC was not adjusted. Since wildlife must be protected at concentrations that are orders of magnitude less than the STLC, raising the STLC would have no impact on hazards to wildlife. Indeed, increasing the legally defined STLC would have an insignificant impact on environmental hazards but would facilitate opportunities to maintain an economically sustainable agriculture production system in the western San Joaquin Valley.Microorganisms, including bacteria, have developed mechanisms to protect themselves from the effects of antibacterial substances for several billion years . Antimicrobial resistance is the capability of microorganisms to survive the effects of antimicrobial agents via various mechanisms, such as a mutation in an existing gene or obtaining resistant genes through horizontal gene transfer . Four main mechanisms of AMR in bacteria are limiting the uptake of a drug, modifying a drug target, inactivating a drug and active drug efflux . Additionally, there are two main biological pathways that enable the evolution and dissemination of resistance: vertical gene transfer and horizontal gene transfer . Although the widespread usage of antibiotics began in the middle of the last century after the discovery of penicillin by Alexander Fleming, antimicrobial resistance has been recognized as a global threat and one of the leading public health problems of the 21st century only over the last two decades . The World Health Organization’s first report on worldwide surveillance of AMR, cannabis equipment which was released in April 2014, showed the seriousness of the AMR problem Many factors are attributed to the emergence and spread of AMR, including overuse and misuse of antimicrobial drugs, poor sanitation, poor practice of disease prevention and control, lack of knowledge, public awareness, legislation and lack of innovation and development of drug resources .
However, overuse or misuse of antimicrobial drugs is considered the leading cause of the emergence and spread of AMR or accelerated development of AMR . Especially, the usage of antimicrobial drugs in food animal production has been considered as one of the contributors to the AMR problem . In the U.S., approximately 2.8 million clinical infections and 35,000 human deaths occur annually . According to an estimate, by 2050, AMR could be the leading cause of mortality, with 10 million deaths, surpassing cancer in the mortality rate . Besides taking polls on people’s lives, AMR causes an economic burden to the patients. It makes diseases and hospital stays longer, medical costs higher, and treatments ineffective and sometimes impossible to treat . Making exact estimates of the burden of AMR is challenging. According to the recent review by Naylor et al. , the economic burden from AMR per case is around $21832 and over $ 3 trillion in GDP loss. The economic burden from AMR in the U.S.,as reported by the Centers for Disease Control and Prevention , is around 4-5 billion dollars every year. It is expected that by 2050, a total global economic cost of US$100 trillion will be attributed to AMR . Long-term exposure to antibiotics might weaken the immune system in humans, cause digestive problems, and have carcinogenic effects . Some infectious diseases easily treatable with penicillin in the past now require second and third-line antibiotics due to AMR. Other medical areas, such as chemotherapy for cancer treatment, organ transplantation, hip replacement surgery, intensive care for pre-term newborns, and many others, depend on the availability of efficient antibiotic drugs. Infections triggered by MDR bacteria are the main contributors to morbidity and mortality in people undergoing the above mentioned procedures. For example, studies have shown high AMR rates in infections in patients with cancer and liver transplantation .
Antimicrobial agents are a semi-synthetic or synthetic substance that kills or inhibits microorganisms . Since the 1940s, antibiotic agents have been used in the livestock industry for disease prevention and treatment and growth promotion. Antimicrobial agents in livestock have yielded healthier and more productive animals with lower disease incidence and reduced morbidity while lowering the cost of animal food production . However, this honeymoon period was short-lived, and these benefits have yielded adverse outcomes: overuse and misuse of antimicrobials in food animal production resulted in an accelerated increase in antimicrobial resistance, and food animals have become reservoirs of antibiotic-resistant bacteria . Antibiotic-resistant bacteria and their genetic determinants can be transferred from food animals to humans via direct or indirect contact or food chains . Increased demand for protein led to the global spread of intensive farming , and antimicrobial usage has become an essential part of intensive farming . Global food animal production increased 4-5-fold since 1961. In turn, intensive farming expansion has led to increased consumption of antimicrobials worldwide . Two-thirds of the total medically important antimicrobials in the U.S. are associated with food animal production . In 2019 alone 11,000 tons of antibiotics were used in animal production . It is projected that the consumption of antimicrobials will rise by 67% by 2030 worldwide, and the rise is likely caused by expected consumer demand for livestock products as the global population and affluent people are increasing in developed countries . According to the Bayesian regression framework conducted by , antimicrobial consumption is expected to increase in pigs and chickens compared to cattle. Antibiotics in food animals can be divided into three categories: therapeutic use, disease prevention, and growth promotion .
Usage of antibiotics for disease prevention and growth promotion in food animals are distinct practices, and they are differentiated based on the purpose of usage, stage of lifecycle, timing of antibiotic administration, and dosage levels. For example, in disease prevention, antibiotics are administered at therapeutic levels , while in growth promotion, antibiotics are administered at subtherapeutic levels . Another example antibiotics for disease prevention are administered for a short period of time before outbreaks, while antibiotics for growth promotion are administered continuously during the animal’s growth phase or over a long period . However, there might still be a blurred line between these two practices. There are still possibilities to use antibiotics as growth promoters despite the U.S. banned growth promoters in 2017. For example, dosing food animals continuously with antibiotics for disease prevention has been used in large-scale farming . Antibiotics are administered via feed, water, or intramuscular injection . Antimicrobials are administered to the entire flock or group in intensive farming via feed or water. The purpose of this practice is to prevent the spread of the disease. However, this practice sometimes results in overuse or misuse of antimicrobials, increasing ARB in animals. Additionally, the occurrence of infectious diseases and usage of antimicrobials depends on endogenous risk factors and farmers’ decision-making, which can be influenced by cost-benefit analysis, farmer’s expertise, and behavior .WHO has recognized the necessity of coordinated global efforts to mitigate the AMR spread and recommended avoiding using antimicrobials in food animal production . New European regulations on veterinary medicine and medicated feed are expected to substantially reduce antimicrobial usage in food animal production throughout Europe in the future . In the U.S., the FDA has been regulating antimicrobial drug prescriptions by implementing stricter policies on using antimicrobials over the years. For example, in 2017, the FDA banned the usage of growth promoters in the production of food animals, vertical grow shelf and in the same year, it also required veterinary prescriptions for “important antimicrobials” defined as Veterinary Feed Directive drugs. Therefore, banning antimicrobials as growth promoters in Europe in 2003, followed by the U.S. in 2017, helped to reduce antimicrobial consumption . For example, in the Netherlands, consumption of antimicrobials decreased by 70 % between 2009 and 2019, and the resistance of some species of bacteria decreased compared to the previous years . FDA has been developing strategies to reduce the usage of antimicrobials in food animal production . For example, in 2015, the FDA updated the new animal drug regulations to put into practice the veterinary feed directive , and according to this update, VFD drugs have been allowed only under the professional oversight of a licensed veterinarian. Recent studies have shown the effectiveness of reducing the usage of antimicrobials in food animal production in taming AMR. For example, the literature review conducted by Tang et al. has shown that restricting antimicrobial usage in food animal production might reduce animal ARB by up to 39 %. However, with an increase in global population and wealthy people in developing countries, demand for animal protein is expected to increase, further challenging the combat to reduce AMR.
Critically important antimicrobials play an essential role in treating life-threatening infectious diseases in humans and animals, and they are considered the last line of defense against some serious infectious illnesses . The List of Critically Important Antimicrobials of WHO for Human Medicine was developed in 2005 and has been updated since, the latest being updated in 2018 . Since its development, the CIA List has been the benchmark for food animal producers worldwide by providing essential guidance . WHO classified antimicrobials into three groups: important, highly important, and critically important. . Most antimicrobial classes on the WHO CIA list belong to the “Critically Important” category, and fewer belong to other groups. Apart from the WHO CIA list, the World Organization for Animal Health created a CIA list, which is a list of essential antimicrobials for veterinary medicine. Additionally, the WHO encourages countries to have their own CIA list, and the U.S. The CIAs have been further classified into high-priority and highest-priority CIAs based on the number of people with infections for which limited antimicrobials are available and the rate of usage among high-risk groups in human medicine . The highest priority CIAs are the quinolones , 3rd and higher-generation cephalosporins, macrolides and ketolides, glycopeptides, and polymyxins . High-priority CIAs are aminoglycosides, penicillins, ansamycins, penems, glycylcyclines, lipopeptides, monobactams, oxazolidinones, and mycobacterial drugs. Highly important antimicrobials are tetracyclines, amphenicols, cephalosporins , lincosamides, pseudomonic acids,riminofenazines, steroid antibacterials, streptogramins, sulfonamides, sulfones. Important antimicrobials are aminocyclitols, cyclic polypeptides, nitrofurantoin, nitroimidazoles, and pleuromutilins . Most antimicrobial classes are common in both veterinary and human medicine; nevertheless, the importance of some antimicrobials might differ based on species and application . According to the World Health Organization’s categorization, critically important antibiotics for human medicine are fluoroquinolones, thirdand fourth-generation cephalosporins, macrolides, glycopeptides, and polymyxins . Penicillin, macrolides, and fluoroquinolones are mainly used to treat human infections, while tetracyclines, penicillin, and sulfonamides are frequently used to treat food animal infections . Not long after its invention, penicillin was used to treat bovine mastitis to sustain the sustain milk supplies during World War II. In 1948 sulfaquinoxaline was used in poultry for the prevention of coccidiosis. In the U.S., antibiotics in livestock were first approved in 1951, giving birth to antibiotic-reliant large-scale food animal production operations . In recent years, in the U.S., antibiotic consumption in chicken production is decreased dramatically. For example, in 2018, ninety-two percent of broilers were produced without using medically important antimicrobials . Penicillin and tetracycline are mostly used in pigs worldwide . In 2012, tetracycline accounted for 41 % of total sold antimicrobials in the U.S. . Extended-spectrum cephalosporins, macrolides, fluoroquinolones, and polymyxins are classes of CIA usedin pigs and cattle worldwide . In the U.S., 43% of all medically essential antimicrobials were consumed in cattle in 2016 In 2017, WHO released recommendations on the utilization of medically important antimicrobials in animal agriculture to keep the effectiveness of medically important antimicrobials. In 2018, the WHO issued guidelines on using HP-CIAs in food-producing animals; the guidelines recommended not to use HP-CIAs for human medicine in treating food animals with infectious disease diagnoses . These measures have been taken to fight antimicrobial resistance and preserve the effectiveness of CIAs.Occupational exposure of animal farm workers to AMR has been largely neglected and unrecognized due to different reasons such as scarce knowledge about AMR burden, lack of adequate regulations, lack or insufficiency of surveillance and monitoring, and economic factors . The chance of transmission of ARB or antibiotic resistance genes from food animals to farm workers is very high based on previous research, which reported that occupational exposure poses a risk to farm workers . Specifically, ARB can be transmitted from animals to farm works through various ways, including direct contact with animals or animal feces or products, inhalation of dust or aerosols containing ARB or ARG, contact with ARB or ARG contaminated surfaces, equipment, tools, water, or food .