Animals could become sick at any time of their lives, just like all people exposed. Many of the antibiotics administered to animals are identical to or closely drugs used in human. All animal species in general and food-producing animals, in particular, are commonly exposed to antibiotics to treat and prevent infectious diseases or to promote growth. Antibiotics would not be necessary if animals were raised differently under good veterinary and husbandry practices that were less crowded and more sanitary. The proper and responsible use of antibiotics in veterinary medicine mandate an active cooperation between all the interested parties involved in livestock production cycles. All parties are invited to act together to ensure the ultimate goals of maintaining the efficacy and safety of veterinary antibiotics and complying the established maximum residue limits (MRLs) of the products of animal origin intended for human consumption. Antibiotics as hazardous substances should be applied and directed during the different steps starting from prescription until ensuring the withdrawal period under the supervision of professionals and veterinarians. Practices indicated that there is a need to improve sensitivity testing services and facilities before prescribing the proper antibiotic.
- resistant bacteria
- food-producing animals
- drug prescription
Since the veterinary antibiotic residues and occurrence of bacterial resistance problems had got the attention of scientists and public communities, many questions raised focusing on the main five logics of (5W + 1H) being: What are the alternatives and choices to avoid using veterinary antibiotics? Why we cannot stop usage of antibiotics in food-producing animals? When do veterinary antibiotics are necessary to use? Where do the herd producers get antibiotics for animal use? Who is authorized to prescribe and regulate antibiotics for animal use? And how could antibiotics be effective without any negative effects on public health?
2. Choices and alternatives to control bacterial infections and diseases in companion and food-producing animals
Undoubtedly, animals could become sick at sometime of their lives, just like all people do. Food-producing animals involving large and small ruminants, poultry and aquaculture are often exposed to antibiotics to treat and prevent infectious diseases or to promote growth [1, 2]. Many of the antibiotics administered to animals are identical to or closely resemble drugs used in human [2, 3]. Also, other animal species like pets, dogs, horses and animals used for fur are commonly exposed to bacterial infections during their lives. These groups of animals when showed clinical signs, they could be treated separately . As an example, when clinical symptoms of infections were reported or suspected in horses, dogs and other companion animals, they could be easily monitored with a possible quarantine. So, the risk of the infection spreading in veterinary hospitals and veterinary clinics could be at minimum. The same approach was followed when dogs showed clinical symptoms, they should not be kept with other animals [5, 6]. The issue is completely different when flocks or herds of food-producing animals are exposed to bacterial diseases or infections . The responsibility of antibiotics in veterinary medicine is still the best choice to control and treat bacterial infections. Guidelines on the responsibility and prudent use of antibiotics in animal husbandry were issued by the United Nation Organization of UN-Office International des Epizooties  and confirmed by the European Union . The aims of the guidelines are to maintain antibiotic efficacy, avoid dissemination of resistant bacteria and finally, avoid such bacteria to reach human food. Also, the guidelines are addressed to all the interested parties involved in animal husbandry; that is, the veterinary pharmaceutical industry, practitioners, breeders and farmers. The guidelines also exhibited the main role and responsibility of the competent authorities dealing with the production and marketing of veterinary antibiotics. The approved guidelines for the use of antibiotics in veterinary medicine had a set of recommendations and measures acting together to ensure the ultimate goals of: (a) comply with the mandatory standards recommended by the international organizations, (b) maintain the efficacy and safety of antibiotics, (c) prevent or at least reduce transformation of resistant bacteria to human, (d) fulfill and comply the established maximum residue limits (MRLs) of the applied antibiotics and finally, (e) ensure the safety of the products of animal origin intended for human consumption.
3. The prudent and responsible use of antibiotics
The technical committee of UN-Office International des Epizooties  recommended the following criteria for the proper and responsible use of antibiotics:
Antibiotics as hazardous substances should be applied and technically directed under the supervision of professionals and those have the required experience and skills.
Antibiotics usage should be applied within the good veterinary practices (GVP) and animal husbandry practices, considering diseases prevention practices like vaccination and improving husbandry conditions.
The usage of antibiotics should be limited to their approved and intended use.
Where appropriate, testing of isolates from food-producing animals during their production period to adjust therapy.
The proper and responsible use of antibiotics in veterinary medicine mandate an active cooperation between all the interested parties involving, administrative and scientific authorities, veterinary pharmaceutical industry, distributors and handlers, veterinary practitioners and livestock breeders and producers.
It is worthy to mention that prudent use of veterinary antibiotics is the most important part of the good veterinary practices (GVP). The first step is commonly dealing with antibiotic prescribing habits. Some practitioners take into account responsible use warnings when antibiotic sensitivity testing is performed. No doubt, those significant differences could be obtained, due to the frequency of sensitivity testing, practitioners skills, background as well as some interfering factors. Practices indicate that there is a need to improve sensitivity testing services and facilities aiming to offer rapid, accurate and cheaper testing before prescribing antibiotics . As more antibiotics are discovered and applied to veterinary clinical use, there is a need to update codes of practices, conduct and ethics. Applying such codes will help to ensure maximizing therapeutic efficacy and minimizing the resistance of microorganisms. Veterinary antibiotics are not only widely used in many countries, if not in all countries to treat and protect animal health, but also they are incorporated into animal feed to improve growth and feed utilization. Regarding antibiotic feed additives, they are poorly absorbed in the gut, so the great portion of such antibiotic additives will take their way into animal secretions such as feces and urine leading to contamination of soil and environment [10, 11, 12]. So, the routine use of antibiotics as growth promoters is no longer recommended. Also, veterinarians, practitioners and livestock breeders should have enough knowledge about infectious diseases exposure pathways, fate and effects of veterinary antibiotics, besides the environmental cycle and occurrence.
4. Antibiotic usage in food-producing animals and aquaculture
4.1. Mass production of beef
Raising beef cattle needs relatively little intervention and use of antibiotics comparing with those managed in intensive and feedlots. But commonly beef calves, after weaning aged 6 months and more, are routinely shipped to mass production farms, then maintained in large groups and fed high energy rations. In most developing countries, feedlot animals are kept at high densities which lead to more morbidity, especially in newly received calves. During such production cycle, both pneumonia and diarrhea are the major threat to the herd life. Bovine respiratory diseases have occurred with many causal organisms. These organisms could change during the progression of diseases . Thus, calves are often treated with individual or grouping medication. Consequently, a variety of viral secondary infections contribute to the primary of pneumonia and diarrhea, but treating bacterial infection is still the right medication. Also, the major feedlot health problem of shipping fever complex of pneumonia is an important determinant of antibiotic use. Since beef cattle change ownership more than once during their life cycles, feedlot owners could not easily followed the good veterinary practices. So, the common approach based on the assumption that animals in the group are either susceptible or already carrying diseases . This assumption is applied in USA, when 83% of feedlot cattle received antibiotics through feed or water . The most commonly used oral antibiotics are tylosin, tetracyclines and florfenicols, which could act as prophylactic treatment against liver abscesses, diarrhea, foot rot and respiratory diseases, as well as acting as growth promoters at sub-therapeutic levels . The relation between antibiotic use and resistance in beef cattle appeared wide conflicting results between calves treated with penicillin, streptomycin and tetracyclines and the resistant
4.2. Dairy production
As dairy industry is increasing, average herd size and average milk production per head had significantly increased. The common system in most dairy farms depends upon the separation of new-born calves from mothers within a day of birth. The new-born calves are housed separately to control infection and fed milk and/or milk replacers commonly contained tetracycline up to the weaning age 6–8 weeks. To treat or prevent the common diseases of pneumonia and diarrhea, the antibiotics of tetracycline, penicillin and sulfonamides may be administered orally or by injection. Dairy cows are commonly housed at higher densities with great metabolic stress. As milk production increases, parallelly related disease increased, which could negatively affect animal welfare and food quality . Contrary to poultry and beef industry, antibiotics in dairy industry are used for therapeutic functions . Antibiotics are very necessary to treat the common diseases of mastitis, lameness, respiratory diseases and gastrointestinal disorders [21, 22]. In most countries, especially the developing ones, intra-mammary use of antibiotics was frequent, with little if no information, about pharmacokinetics, efficacy and withdrawal period. So, antibiotics use in dairy cattle should be related to the production stage “lactation, dry period and heifers replacement”. In lactating dairy cows, mastitis is the most common challenge of diseases. Mastitis caused by intra-mammary infections which could be categorized as clinical or sub-clinical based on clinical signs and some milk composition criteria . To select an appropriate therapeutic protocol, it necessitates enough data about: clinical signs, milk composition and the results of sensitivity testing . Some forms of chronic mastitis like those caused by
4.3. Small ruminants
Sheep and goats are farmed for different products, that is, milk, meat and wool. Sheep and goats necessitate the use of antibiotics to treat the common diseases of mastitis, lameness, respiratory and gastrointestinal disorders [21, 22]. The licensed antibiotics for sheep and goats are very rare, so the use of such drugs depends upon the practitioners experience. Dosage estimation and withdrawal time had not adequately reported for sheep and goats, which increases the risk of residues in human food . The use of antibiotics in small ruminants is relatively low, especially with meat sheep. For therapeutic use, penicillin and tetracyclines are the most common antibiotics, meanwhile tetracycline was more common in feed medication . Usually, small ruminants mastitis is sub-clinical and does not necessarily reduce milk yield and often localized to one udder half. The main adverse effects are related to milk quality and increasing somatic cells counts (SCC) in the yield. It is well established that high SCC are positively related to increase antibiotic residues . Because of the rare antibiotics labeled for small ruminants, mastitis is commonly treated with bovine intra-mammary products, which leads to many adverse effects due to the improper dosage and the estimated withdrawal period . In small ruminants, both broad and narrow spectrum antibiotics can enhance animal performance .
Poultry products including eggs and meat are very important sources of animal protein in most developed and developing counties. During the last five decades, broiler chicken production all over the world had increased significantly to meet the increased requirement of animal protein. In Egypt, as an example, poultry industry were grew fast to be highly integrated industry with fewer companies controlling most sources of birds, feed mills, farms, slaughter and processing facilities. Integration of such industry led to standardized management practices including drug treatment practices, especially those related to prevent and control of infection diseases. An intensive production system resulted the spread of pathogens including the zoonotic ones like
4.5. Fish aquaculture
Antibiotics are very essential additions in fish aquaculture. The ability of antibiotics to control fish diseases is influenced by four main factors: (1) the actual bacterial component, (2) the sensitivity and/or resistance of the bacterial strains to the chosen antibiotic, (3) the proper dosage and treatment intervals and (4) the other contributing stress factors. Antibiotics do not directly cure treated fish, but they are controlling the population growth of a bacteria in a fish which promoting their immune system to eliminate them . Before antibiotics are prescribed to fish and aquaculture, sources of stress involved water quality and temperature, differences between aquaculture species, nutrition and means of antibiotics handling and transportation should be eliminated or at least minimized . Special experience and skills are needed to identify the interfered factors which could be primary or secondary factors affecting bacterial infectious diseases. Such experience and skills besides the sensitivity testing could lead to more efficient treatments and less loss of fish.
5. Persistence development of bacterial resistance threaten human health and environment
Many reports exhibited the variable resistant response of bacterial pathogens [40, 41]. Resistant species of
6. Cautions and precautions before prescribing veterinary antibiotics
When it is necessary to use veterinary antibiotics to safeguard animal health, many precautions should be considered:
The prescription should be based on clinical diagnosis by qualified veterinarian and conducting sensitivity testing to choose the proper antibiotic .
In general, metaphylaxis antibiotics should never be used, when good veterinary and husbandry practices are available .
Metaphylaxis antibiotics, when it is necessary, should be prescribed on the basis of clinical findings about the progress of a disease in certain herd or flock .
It is much better to isolate and separate sick animals and treated them individually .
Livestock producers should keep files and records to register causes and nature of infections and the available antibiotic products to facilitate the right and correct decision .
Narrow-spectrum antibiotics could be the first choice, unless sensitivity testing exhibit that they could be ineffective. Contrary, the broad-spectrum antibiotics should be avoided .
In re-current infection cases, tracing the causal bacteria is recommended to determine why the disease is recurring and to facilitate the pathogenic microorganisms eradication .
The need for antibiotic therapy should be reassessed on scientific basis to avoid unnecessary medications.
Antibiotics should be administered as the instructions of the prescriber and the manufacturer of the drug .
All alternative programs to control diseases like vaccination, good veterinary and husbandry practices should be applied together to minimize or reduce the need to veterinary antibiotics .
Advanced laboratories are recommended to perform rapid and accurate sensitivity testing and more advanced once are required to evaluate and control zoonotic and commensal microorganisms .
The common cases necessitate the usage of antibiotics in animals were summarized in Figure 1 .
7. Economic considerations
It is well agreed and understood that agriculture is practiced to return profit to the farmers and livestock producers. So, two main economic considerations influence the selected programs adopted by livestock producers. The first limiting factor is to select and elect individuals or animal flocks capable to challenge diseases, and the second one is the response of elected animals to enhance most production parameters. It is more economical to prevent diseases than treating them. The preventive efforts involve variety of practices including, proper nutrition, immunization, good veterinary and husbandry practices . Prevention is needed for many diseases and it will be necessary to use prophylactic antibiotics during certain critical periods of animal life. Referring to the second consideration aiming to the response to enhancing most production parameters, livestock producer has the option to do or do not using antibiotics . An economic evaluation of antibiotic usage in animal agriculture is calculated on the basis of return on such use which is not easy to quantify when used as prophylaxis. When antibiotics are used to treat diseases, it is easy to quantify the return, because the cost represents a portion of the necessary total expenses. In both cases, many factors should be considered, that is, costs of diagnosis, culture and sensitivity testing, confirmatory tests and the estimated loss of production based on the affected animals. Actually, the economic return on the use of antibiotics for prevention could be determined by direct comparison with similar farms not using antibiotics. Sub-therapeutic antibiotics are commonly administered to protect animal populations during the critical time when they are susceptible or expose to specific infections and hazards . Thus, such approaches could be considered as economically cost effective, since they reduce the necessity of using higher therapeutic levels of antibiotics.
8. Risk and impact of veterinary antibiotics on human health and environment
Recently, there is a great concern between public in general and scientific communities, in particular, that exposure to pharmaceuticals including antibiotics may have negative effects on both human health and environment . The adverse effects on human health may include the risk of chemical poisoning [51, 52], hypersensitivity reaction, especially with penicillin [53, 54], liver injuries , disruption in the normal intestinal flora  and occurrence of antibiotic resistance [54, 57]. The adverse effects of exposure to veterinary antibiotic residues in food is very difficult to trace, because bacterial resistance could take very long period of time. For example, the antibiotic chloramphenicol which used in human medicine to treat severe illness, when used as veterinary medicine for food-producing animals, dramatic effects were observed. Thus US-FDA banned the use of chloramphenicol in food-producing animals; even they approved the utility of the drug in treating systemic infections in cattle . Also, because there is no threshold predicted for human aplastic anemia, chloramphenicol is completely banned for use in food-producing animals in many countries including Australia, Canada, EU and USA . It is worthy to mention that chloramphenicol can be synthesized in soil which could be reached to feedstuffs consequently to the edible tissues of the animals. The Codex Committee on veterinary residues had recommended certain criteria for risk assessment of chloramphenicol or any antibiotic when used in food-producing animals . Such criteria evaluate the potential of both short and long term of dietary exposure to antibiotic(s) residues on human health. However, misuse of antibiotics in animal husbandry and aquaculture could lead to the presence of residues in human food .
Transformation of antibiotic residues could easily reach soil, surface and ground water via many routes such as sub-surface flow, drain flow or leaching [11, 58]. The concentration of the transformed residues are affected by many factors including the chemical and physical properties of the antibiotic molecule, sorption behavior and persistence, exchange capacity of the soil matrix besides the various climate conditions . Recent reports showed that sulfonamides and chloramphenicol could easily reach ground water, while fluoroquinolones could not leach. The reports added that in most areas of intensive livestock breeding, the source of contamination mainly attributed to irrigation with sewage [12, 16]. The uptake and accumulation of antibiotics into edible plants is commonly initiated when expose to contaminated soil with considerable concentrations of the drugs over time as confirmed by several studies [59, 60, 61, 62, 63]. However significant amounts of antibiotics and/or their degraded metabolites are introduced to agro-system via irrigation, fertilization with antibiotic-polluted manures, bio-solids, sludge, sediments and contaminated water [16, 64]. Accumulation and transport of antibiotics to edible plants poses high risk to crops, soil and water eco-systems [63, 65, 66], consequently, increasing risk to both human health and environment . Applying and implementing good veterinary and husbandry practices are most urgent issues to control and reduce both the problems of antibiotic residue contamination and persistence of resistant bacteria.