Antibiotics

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Antibiotics are commonly administered to food animals both therapeutically and subtherapeutically. Several classes of antibiotics are used in livestock veterinary medicine. Sulfonamides are derivatives of sulfanilamide, one of the first drugs discovered to treat Streptococcal infections. Sulfamethazine and sulfadimethoxide are shown as examples of this class of drugs in Figure 1. Although not technically classified as antibiotics, these drugs are bacteriostatic agents that effectively interfere with the synthesis of folic acid in susceptible organisms and are widely used in both humans and food-producing animals to prevent infectious diseases [3].

Penicillin is one example of a b-lactam antibiotic historically used in veterinary medicine. All antibiotics in this class contain a b-lactam ring [4]. Many b-lactams approved as animal drugs are based on the penicillin molecule, including ampicillin, amoxicillin and cloxacillin. Cephapirin and ceftioflur, however, contain a cephalosporin nucleus. These drugs are effective in cattle that are fighting against mastitis as well as respiratory and intestinal infections. They are also administered to swine and allowed to be used in some countries for farm-raised finfish.

Aminoglycoside drugs are antibiotics effective against most gram-positive and negative organisms. They are isolated from Streptomyces or Micromonospora species and their mode of action is to interfere with bacterial protein synthesis. These drugs consist of linked amino sugar groups; examples include streptomycin, apramycin, dihydrostreptomycin, gentamicin and neomycin (Figure 1). They are administered both therapeutically and prophylatically to treat cattle, swine and poultry [5]. Aminoglycosides are not absorbed orally and so are usually administered via intramuscular injection. Residues of these drugs tend to concentrate in the kidney as they are generally excreted through the urinary tract.

Tetracyclines are broad-spectrum antibiotics that inhibit protein synthesis in bacterial cell walls. They consist of a substituted 2-napthacenecarboxamide molecule. These antibiotics were originally isolated from Streptomyces. The most common tetracyclines with animal health applications are tetracycline, oxyte-tracycline and chlortetracycline [6]. In the U.S., these drugs have been approved for beef cattle, calves, swine, sheep, chickens and turkeys. Oxytetracycline has been specifically approved for use in dairy cattle and aquacultured catfish, salmon and lobster. This drug has not been approved by the U.S. for shrimp aquaculture, although it is believed to be used widely in shrimp production in other parts of the world.

Sulfamethazine

Sulfamethazine

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Sulfadimethoxine h,c ch,

"ch, oh o oh o o Oxytetracycline h-n-

r h h oh o oh o o Oxytetracycline

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Sarafloxacin

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Neomycin nh,

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Figure 1 Structures of antibiotics [2].

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Fenbendazole

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Levamisole

Levamisole

Figure 2 Structures of anthelmintics and antifungals [2].

Figure 2 Structures of anthelmintics and antifungals [2].

Another class of antibiotics originally isolated from the Streptomyces species is the macrolides [7]. Macrolides are multi-membered lactone rings with one or more sugars attached. These drugs are most effective against gram-positive organisms and some strains of Listeria and Mycoplasma. Erythromycin (Figure 1) and tylosin are the drugs most commonly given to food-producing animals. Oleandomycin, spiramycin, sedamycin and tilmicosin are also used therapeuti-cally to treat bovine respiratory diseases and mastitis and swine dysentery, or used as a feed additive to promote growth efficiency. Macrolides can also be added to the food and water supplies for chickens and turkeys to prevent respiratory disease and enteritis, as well as to promote growth. These drugs are also effective in treating bee colonies for brood disease. Although their chemical

Xylazine

COOH Flunixin

COOH Flunixin

Xylazine

Phenylbutazone

Figure 3 Structures of tranquilizers and anti-inflammatory drugs [2].

structure is quite different, the lincosamide antibiotics (lincomycin and pirlimycin) have similar antibacterial activity, clinical applications and cellular mechanisms as the macrolides.

Quinolones are pyridone carboxylic acid derivatives that are effective against gram-negative bacteria. Examples of quinolone drugs include oxolinic, nalidixic and piromidic acids. Quinolones have been found to be effective as a prophylactic treatment for aquacultured species; they have also been investigated by the swine and poultry industry. Fluoroquinolones are the fluorinated subclass of the quinolones that also exhibit activity towards gram-positive bacteria [8]. Sarafloxacin, enrofloxacin, difloxacin, ciprofloxacin, norfloxacin and ofloxacin are just some examples of fluoroquinolones. As is discussed later, there are growing concerns with the use of these drugs in foods of animal origin due to the problem of increased antibiotic resistance associated with this subclass of antibiotics.

Compounds that retard the development of a parasite in a host cell are known as coccidiostats. A common class of drugs used for this purpose is the ionophores, which include monensin (Figure 1), salinomycin and lasalocid [9]. Other drugs such as amprolium, clopidol, halofuginone, nicarbazin and even the tetracyclines can also be effective coccidiostats. While these drugs are most commonly given to poultry populations, monensin, lasalocid and amprolium can

also be administered to cattle to treat coccidiosis. The ionophores may also be used to promote growth in cattle.

Another class of drugs used in veterinary medicine is the peptide antibiotics including bacitracin, colistin, virginiamycin and avoparcin. Each of these drugs are actually a mixture of peptides produced by Bacillus and Streptomyces species and may be glycosylated in some positions. They are primarily added to animal feed to enhance growth. There are concerns regarding antibiotic resistance from glycopeptides because of their structural similarity to the human drug vancomycin [10].

Other antibiotic classes that will be discussed in further detail later in the chapter include the nitrofurans and the phenicols such as chloramphenicol and florfenicol. Representative drugs from these classes of antibiotics are also included in Figure 1.

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