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Antimicrobial drug use in swine has always been substantial and in some cases, the swine industry has been considered over-reliant on their use. As farms have evolved from small back-yard operations, only 50 years ago, to today's substantially larger units, it is not surprising that antibiotics have been used to help farmers maintain their production under these major management, housing and disease pattern changes. It must be remembered that antibiotics have a cost and that farmers are unlikely to pay for them unless they can see a benefit from their use.
Swine farming has made great steps forward in management and husbandry systems to reduce antimicro- bial use. Examples are the improvement of biosecurity (keeping diseases out), sourcing of high-health genetic stock and the utilization of 3-site production. The latter enables "all-in and all-out"¯ procedures to be followed with the accompanying improvements in hygiene and infection control and the prevention of back infection from older pigs on the farm. Unlike the broiler industry, which pioneered this system and where stock is reared for only 5-6 weeks before slaughter, pigs are raised for nearly 6 months, making it not so easy to follow. In farrow-to-finish operations, often family farms, which are still the most common operation, there is still a need for antimicrobial medication to assist with health and production, in spite of the use of vaccination, as not all diseases can be controlled sufficiently that way.
Concerns regarding antimicrobial use in animals and their relation to man regarding resistance transmission via zoonotic bacteria such as Salmonella spp., Campylobacter coli, and more recently methicillin- resistant Staphylococcus aureus (MRSA) or more indirectly via Escherichia coli or Enterococcus spp. is under huge review at the moment and a number of changes can be anticipated over the next 5 years. In the United States there are calls to ban the use of antibiotic growth promoters and only use antimicrobials for prevention and treatment (see chapter 22). The European Union (EU) banned the use of antimicrobial growth promoters in 2006, and now there are calls from the European Parliament to go a step further and stop all prophylactic use. The United States has banned the use of fluoroquinolones in poultry (drinking water use) but permitted the use of injectables in swine, but in Europe there are calls to ban the use of all fluoroquinolones and third- and fourth-generation cephalosporins in veterinary medicine. The United States has already put restrictions on the use of all cephalosporins to "on-label"¯ use only and in the EU the cessation of use is being implemented for third-generation cephalosporins, such as ceftiofur, in the poultry industry.
The swine industry in conjunction with other industries is advocating the responsible use of antimicrobials via various bodies such as the UK's "Responsible Use of Medicines Alliance" (RUMA), the EU via EPRUMA and the United States via their National Pork Board. This is seen as the only way forward to maintain the availability of antimicrobials, which are needed in veterinary medicine to treat and prevent dis- ease and to maintain the health and welfare of the animals under their care. At the same time, efforts are being made to reduce unnecessary use and the use of critical human antibiotics where suitable alternatives are available. In the EU antimicrobial drugs are prescription-only medicines (POMs) and used under veterinary supervision or prescription. In the United States, their use is much freer, in that many drugs can be used in feed without a prescription but their inclusion level is normally regulated by the feed mill. This may also change in the future. In some EU countries, the use of antimicrobials in feed is being stopped; for example, in the Netherlands, in an attempt to reduce overall antimicrobial usage, and it is strongly restricted in Germany and Denmark. However, neither the third- and fourth- generation cephalosporins nor fluoroquinolones are used in feed in the EU.
Responsible use calls for vets and farmers to use antimicrobials "as little as possible but as much as needed".¯ There are a number of guidelines on how to use antimi crobials properly and it is the aim of this chapter to help with the decision making regarding the right antibiotic for the right infection, to be administered at the right dose via the appropriate route.
Antimicrobial Administration in Swine
In general, the injection of pigs, other than baby piglets, is laborious and is used primarily to treat clinically ill pigs either with acute respiratory infections such as Actinobacillus pleuropneumoniae or enteric infections such as swine dysentery caused by Brachyspira hyodysenteriae, which may be too sick to eat or drink. It is a highly effective route of administration to an individual animal, but many antibiotics require repeated injections on a daily basis. The development of long-acting formulations has improved the issue regarding compliance, to complete the course of treatment. There has been an increase in the prophylactic use of third-generation cephalosporins in baby piglets to prevent a variety of wound infections post-processing (tail docking and castration) and also early infections with Streptococcus suis and Haemophilus parasuis. This may have triggered the selection of MRSA clones (specifically CC398), which has become widespread on the continent of Europe (Anon., 2009) and also in North America (Khanna et al., 2008). It has also probably led to the very high level of resistance (41.8%) to ceftiofur that has been reported in isolates of porcine E. coli from clinical cases in the United States (Frana et al., 2012).Oral administration of antibiotics is the most common route of application in swine medicine. Piglets may be treated individually by oral dosers containing anti- biotics. These have proved most useful for the control of neonatal usually associated with E. coli and gut active and systemically active formulations of enrofloxacin, trimethoprim/sulfonamide and amoxycillin have proved very effective. Later on, when the infection is primarily in the gut, gut-active antibiotics, such as the aminoglycosides neomycin, aminocyclitol spectinomycin and the polymixin colistin, are widely used. Toltrazuril is also highly effective for the prevention and treatment of coccidiosis caused by Isospora suis in piglets.
Water medication is widely used and in some countries becoming more popular due to the introduction of effective automatic dosing machines. In the past it was limited to pen troughs or individual pen tanks. Larger header tanks allowed whole sheds/barns to be treated but in some cases it was difficult depending on the size of tank and frequently required 2-3 applications of a drug each day to ensure an adequate intake and duration of activity. Automatic water proportioner machines, where the antibiotic is dissolved in a concentrate, which flows into the main water system at a set target rate (approximately 1-2%, depending on the solubility of the drug) have proved most popular on larger sites. However, the antibiotic needs to be sufficiently soluble. In many cases the advantages of prompt treatment, controlled dose rates and duration of treatment has helped the replacement of medication via the feed for treatment purposes.
Feed medication in most countries is still the main route of antimicrobial administration in the swine industry. For treatment of disease it can be argued that it is not the most efficient route of administration, as it may take some days for the feed to be manufactured, delivered and work through the storage bin system to get to the pigs. For ease of administration, it is the simplest route. For the prevention of disease, for the early treatment (metaphylaxis), it is ideal, as it can be planned that the pigs receive the medicated feed on arrival or transfer from one shed/barn to another, especially when they are known to come from an infected source. The aim of metaphylaxis is to eliminate or reduce as much as possible the infectious agent, so that it does not cause disease in the next growing phase. The drug is administered at a therapeutic dose in an attempt to eliminate the infection, whether it is B. hyodysenteriae or S. suis. Low concentrations of bacteria (say 102) respond better to lower levels of antibiotic and are less likely to mutate than high concentrations of microorganisms (>106); Drlica, 2003), which are found in clinical infections. This actually supports early treatment or preventative use rather than waiting for high levels of disease before treatment. Antibiotics are often used at lower levels to prevent infection or re-infection from a contaminated environment, especially in the case of swine dysentery. The concentrations in feed are generally lower than the treatment level but are effectively inhibitory, preventing the multiplication of the organism, so to be effective drug concentrations in the gut contents must exceed the minimum inhibitory concentration (MIC) of the bacterium. In some countries, like the United States, antibiotics can be still used for growth promotion. This is sometimes a gray area between prevention concentrations and sub-inhibitory concentrations, which can produce improvements in growth rate and feed conversion efficiency. Many successful growth promoters actually have a prevention of disease effect/claim, such as virginiamycin, prevents Clostridium perfringens infections; carbadox prevents swine dysentery (B. hyodysenteriae) and tylosin prevents porcine proliferative enteropathy "ileitis"¯ Lawsonia intracellularis). This possibly explains the reason why it could be relatively easy for a switch from growth promotion claims to prevention claims for some of these antimicrobials.
There are some pharmacokinetic disadvantages to administering medication via the feed, as sometimes the feed interferes with the absorption of a drug and reduces its bioavailability (Nielsen, 1997) and thereby plasma concentrations. This can have an impact particularly when treating systemic or respiratory infections (Figure 33.1).
On the other hand, oral medication whether by water or in feed is very effective for treating enteric infections, especially E. coli, Salmonella spp., C. perfringens, L. intracellularis and Brachyspira spp., as effective drug concentrations in the gut contents, whether it is in the jejunum, ileum or colon, is critical to their effect (Figure 33.2).
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