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" The Use of Antibiotic in Food Producing Animals ,
                 Benefit and Risk "




                  Done by: Dina




                        I
Introduction


 Like humans, animals can become ill and may need treatment for a bacterial
infection. In this situation, the veterinary surgeon may decide that a course of a
therapeutic antimicrobial is necessary.

  An antibiotic is a chemotherapeutic agent that inhibits or abolishes the growth of
micro-organisms, such as bacteria, fungi, or protozoan , but resistance in bacteria to
particular antibiotics is often rapidly acquired through mutation.

  The term originally referred to any agent with biological activity against living organisms;
however, "antibiotic" now is used to refer to substances with anti-bacterial, anti-fungal, or
anti-parasitical activity. The first antibiotic compounds used in modern medicine were
produced and isolated from living organisms, such as the penicillin class produced by fungi
in the genus Penicillium, or streptomycin from bacteria of the genus Streptomyces. With
advances in organic chemistry many antibiotics are now also obtained by chemical
synthesis , such as the sulfa drugs. Many antibiotics are relatively small molecules with a
molecular weight less than 2000 Da.

  It is estimated that greater than 50% of the antibiotics used in U.S. are given to feed
animals (e.g. chickens, pigs and cattle) in the absence of disease. Antibiotic use in food
animal production has been associated with the emergence of antibiotic-resistant strains of
bacteria including Salmonella spp., Campylobacter spp., Escherichia coli, and
Enterococcus spp. Evidence from some US and European studies suggest that these
resistant bacteria cause infections in humans that do not respond to commonly prescribed
antibiotics. In response to these practices and attendant problems, several organizations
(e.g. The American Society for Microbiology (ASM), American Public Health Association
(APHA) and the American Medical Association (AMA)) have called for restrictions on
antibiotic use in food animal production and an end to all non-therapeutic uses .

  However, delays in regulatory and legislative actions to limit the use of antibiotics are
common, and may include resistance to these changes by industries using or selling
antibiotics, as well as time spend on research to establish causal links between antibiotic
use and emergence of untreatable bacterial diseases. Today, there are two federal bills
(S.742 and H.R. 2562) aimed at phasing out non-therapeutic antibiotics in US food animal
production.




Why are antibiotics used in food-producing animals?
  Antibiotics are used in food-producing animals for three major reasons:

 First, antibiotics are used to treat sick animals.

 Second, antibiotics are used in the absence of disease to prevent diseases during times
when animals may be susceptible to infections. This use affects a larger number of animals,
because it usually involves treating a whole herd or flock, which increases the likelihood of
selecting for organisms that are resistant to the antibiotic. In these two examples, high doses
of antibiotics are used for short periods of time.




                                              II
Third, antibiotics are commonly given in the feed at low doses for long periods to promote
the growth of cattle, poultry, and swine. In the 1950s studies showed that animals given low
doses of antibiotics gained more weight for a given amount of feed than untreated animals.
Exactly how this occurs is unknown. This effect appears to be less effective or absent in
animal production settings with good sanitation.


Which antibiotics used in food-producing animals are related
to antibiotics used in humans?
  The majority of antibiotics used in food animals belong to classes of antibiotics, which are
also used to treat human illness; these include tetracycline, sulfonamides, penicillin,
microclines, fluoroquinolones, cephalosporin, amino glycosides, chloramphenicols, and
streptogramins. Because these classes of antibiotics are similar, then bacteria resistant to
antibiotics used in animals will also be resistant to antibiotics used in humans




Examples :
Fluoroquinolones


What are fluoroquinolones?
  Fluoroquinolones are a modern group of therapeutic antimicrobials, active against a
range of bacteria.

With most therapeutic antimicrobials used to treat bacterial infection in animals there are
related antimicrobials used in human medicine from the same family, so there are
fluoroquinolones used in animal medicines and fluoroquinolones used in human medicines.

This is inevitable because frequently similar bacteria cause disease in humans and animals
and so have to be treated with similar antimicrobials.

All therapeutic antimicrobials are Prescription Only Medicines (POM) are only available on
prescription from a veterinary surgeon.

Marketing Authorization
  Therapeutic antimicrobials must pass strict examination by the Veterinary Medicines
Directorate and fulfill criteria of safety, quality and efficacy before being allowed a
Marketing Authorization for use in animal health. 'Safety' includes safety to the treated
animal, the user, the environment and, for farm animals, the consumer.

In products used for farm livestock, a withdrawal period is calculated i.e. the time that must
follow after the last treatment before the animal, or its produce, can be used for human
consumption.

How are fluoroquinolones given?
 Around half a dozen fluoroquinolones have marketing authorizations in the UK, for use in
dogs, cats, cattle, pigs, chickens and turkeys.




                                            III
When dogs and cats need antimicrobials, the veterinary surgeon treats an individual
animal. A combination of fluoroquinolone injections and tablets may be used. Other pet
animals may have medicines administered orally in water or milk. Cattle and pigs are
treated on an individual basis with oral or injectable products.

  When chickens or turkeys become ill, it is necessary to treat all in-contact birds i.e. all the
birds in the one shed. Some birds will be showing clinical signs whereas some, although
they may appear clinically normal, may be incubating the disease. Fluoroquinolones are
given in the drinking water for a short period of time under the direction of the prescribing
veterinary surgeon.

Why is there concern about their use in animals?
  For some time now, scientists have been debating whether the use of antimicrobials in
veterinary medicine could have an adverse impact on human medicine. At the core of the
debate is the fact that treatment of bacteria with antimicrobials can lead to the development
of resistance. It is postulated that, if these bacteria are passed from animals to humans
through the food chain, then reduction in the clinical efficacy of an antimicrobial could be
possible. However, a World Health Organization meeting in 1998, while stressing the need
for care in the use of fluoroquinolones, did not find clear evidence of harm to man from use
in animals.

Nevertheless, in the US, the FDA/CVM have proposed to withdraw the use of
fluoroquinolones in poultry. This proposal has been addressed very positively by industry.




penicillin
  some drugs have retained excellent activity against particular target organisms, such as the
penicillin against Streptococcus agalactia despite extensive use for 40 years. development of
resistance to animal antimicrobials may present a hazard to humans when the resistant
bacteria can cause disease in humans and can be transmitted via contaminated food.
Bacteria from animals which do not cause human disease may still present a hazard when
transferred via food if they then transfer their genetic material coding for resistance to
pathogenic human bacteria. Clearly a risk to humans exists when the antimicrobial used in
animals is also used in humans or displays cross resistance with an antimicrobial used in
human medicine. This risk has not been quantified.




lincomycin and tylosin
  Antibiotics of the macrolide-lincosamide group have been used in treating food animals
worldwide for several decades. The most commonly used agents have been lincomycin and
tylosin for controlling dysentery and Mycoplasma infections in swine and spiramycin for
treating mastitis in cattle. For the past 20 years, tylosin has also been the most commonly
used agent for growth promotion in swine production worldwide, whereas spiramycin has
been commonly used in poultry. The use of macrolides for growth promotion has been
banned in all European Union countries since July 1999.




                                             IV
Phenylbutazone
   Phenylbutazone became available for use in humans for the treatment of rheumatoid
arthritis and gout in (1949), but is no longer approved, and thus not marketed, for any human
use in the United States. This is because some patients treated with phenylbutazone have
experienced severe toxic reactions, and other effective, less toxic drugs are available to treat
the same conditions.

   Phenylbutazone is known for its ulcerogenic, nephrotoxic, and hemotoxic effects in horses,
dogs, rats, and humans. It is known to induce blood dyscrasias, including aplastic anemia,
leukopenia, agranulocytosis, thrombocytopenia, and deaths. The reported adverse reactions
were associated with the human clinical use of 200 to 800 milligrams phenylbutazone per
day. Hypersensitivity reactions of the serum-sickness type have also been reported in
patients with phenylbutazone. The threshold for this effect has not been defined. Therefore, it
is unclear what level of exposure would be required to trigger such reactions in sensitive
people. Moreover, phenylbutazone is a carcinogen, as determined by the National Toxicology
Program (NTP) based on positive results in genotoxicity tests and some evidence of
carcinogenicity seen in the rat and mouse in carcinogenicity bioassays NTP conducted.

   For animals, phenylbutazone is currently approved only for oral and injectable use in dogs
and horses. Use in horses is limited to use in horses not intended for food. There are
currently no approved uses of phenylbutazone in food-producing animals.
   Investigation by FDA and state regulatory counterparts has recently found phenylbutazone
on farms and identified tissue residues in culled dairy cattle. In addition, the U.S. Department
of Agriculture's (USDA's) Food Safety Inspection Service has reported phenylbutazone
residues in culled cattle presented for slaughter for human food throughout the United States
in the past 2 calendar years. This evidence indicates that the extralabel use of
phenylbutazone in female dairy cattle 20 months of age or older will likely result in the
presence, at slaughter, of residues that are toxic to humans, including being carcinogenic, at
levels that have not been shown to be safe. Because of the likelihood of this adverse event,
we are issuing an order prohibiting the extralabel use of phenylbutazone drugs in female
dairy cattle 20 months of age or older.

   We will continue to monitor the extralabel use of phenylbutazone and will adjust the scope
of this prohibition should we find that extralabel use in other species or classes of animals
presents a risk to public health.




                                             V

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The Use Of Antibiotic In Food Producing Animals ,

  • 1. " The Use of Antibiotic in Food Producing Animals , Benefit and Risk " Done by: Dina I
  • 2. Introduction Like humans, animals can become ill and may need treatment for a bacterial infection. In this situation, the veterinary surgeon may decide that a course of a therapeutic antimicrobial is necessary. An antibiotic is a chemotherapeutic agent that inhibits or abolishes the growth of micro-organisms, such as bacteria, fungi, or protozoan , but resistance in bacteria to particular antibiotics is often rapidly acquired through mutation. The term originally referred to any agent with biological activity against living organisms; however, "antibiotic" now is used to refer to substances with anti-bacterial, anti-fungal, or anti-parasitical activity. The first antibiotic compounds used in modern medicine were produced and isolated from living organisms, such as the penicillin class produced by fungi in the genus Penicillium, or streptomycin from bacteria of the genus Streptomyces. With advances in organic chemistry many antibiotics are now also obtained by chemical synthesis , such as the sulfa drugs. Many antibiotics are relatively small molecules with a molecular weight less than 2000 Da. It is estimated that greater than 50% of the antibiotics used in U.S. are given to feed animals (e.g. chickens, pigs and cattle) in the absence of disease. Antibiotic use in food animal production has been associated with the emergence of antibiotic-resistant strains of bacteria including Salmonella spp., Campylobacter spp., Escherichia coli, and Enterococcus spp. Evidence from some US and European studies suggest that these resistant bacteria cause infections in humans that do not respond to commonly prescribed antibiotics. In response to these practices and attendant problems, several organizations (e.g. The American Society for Microbiology (ASM), American Public Health Association (APHA) and the American Medical Association (AMA)) have called for restrictions on antibiotic use in food animal production and an end to all non-therapeutic uses . However, delays in regulatory and legislative actions to limit the use of antibiotics are common, and may include resistance to these changes by industries using or selling antibiotics, as well as time spend on research to establish causal links between antibiotic use and emergence of untreatable bacterial diseases. Today, there are two federal bills (S.742 and H.R. 2562) aimed at phasing out non-therapeutic antibiotics in US food animal production. Why are antibiotics used in food-producing animals? Antibiotics are used in food-producing animals for three major reasons: First, antibiotics are used to treat sick animals. Second, antibiotics are used in the absence of disease to prevent diseases during times when animals may be susceptible to infections. This use affects a larger number of animals, because it usually involves treating a whole herd or flock, which increases the likelihood of selecting for organisms that are resistant to the antibiotic. In these two examples, high doses of antibiotics are used for short periods of time. II
  • 3. Third, antibiotics are commonly given in the feed at low doses for long periods to promote the growth of cattle, poultry, and swine. In the 1950s studies showed that animals given low doses of antibiotics gained more weight for a given amount of feed than untreated animals. Exactly how this occurs is unknown. This effect appears to be less effective or absent in animal production settings with good sanitation. Which antibiotics used in food-producing animals are related to antibiotics used in humans? The majority of antibiotics used in food animals belong to classes of antibiotics, which are also used to treat human illness; these include tetracycline, sulfonamides, penicillin, microclines, fluoroquinolones, cephalosporin, amino glycosides, chloramphenicols, and streptogramins. Because these classes of antibiotics are similar, then bacteria resistant to antibiotics used in animals will also be resistant to antibiotics used in humans Examples : Fluoroquinolones What are fluoroquinolones? Fluoroquinolones are a modern group of therapeutic antimicrobials, active against a range of bacteria. With most therapeutic antimicrobials used to treat bacterial infection in animals there are related antimicrobials used in human medicine from the same family, so there are fluoroquinolones used in animal medicines and fluoroquinolones used in human medicines. This is inevitable because frequently similar bacteria cause disease in humans and animals and so have to be treated with similar antimicrobials. All therapeutic antimicrobials are Prescription Only Medicines (POM) are only available on prescription from a veterinary surgeon. Marketing Authorization Therapeutic antimicrobials must pass strict examination by the Veterinary Medicines Directorate and fulfill criteria of safety, quality and efficacy before being allowed a Marketing Authorization for use in animal health. 'Safety' includes safety to the treated animal, the user, the environment and, for farm animals, the consumer. In products used for farm livestock, a withdrawal period is calculated i.e. the time that must follow after the last treatment before the animal, or its produce, can be used for human consumption. How are fluoroquinolones given? Around half a dozen fluoroquinolones have marketing authorizations in the UK, for use in dogs, cats, cattle, pigs, chickens and turkeys. III
  • 4. When dogs and cats need antimicrobials, the veterinary surgeon treats an individual animal. A combination of fluoroquinolone injections and tablets may be used. Other pet animals may have medicines administered orally in water or milk. Cattle and pigs are treated on an individual basis with oral or injectable products. When chickens or turkeys become ill, it is necessary to treat all in-contact birds i.e. all the birds in the one shed. Some birds will be showing clinical signs whereas some, although they may appear clinically normal, may be incubating the disease. Fluoroquinolones are given in the drinking water for a short period of time under the direction of the prescribing veterinary surgeon. Why is there concern about their use in animals? For some time now, scientists have been debating whether the use of antimicrobials in veterinary medicine could have an adverse impact on human medicine. At the core of the debate is the fact that treatment of bacteria with antimicrobials can lead to the development of resistance. It is postulated that, if these bacteria are passed from animals to humans through the food chain, then reduction in the clinical efficacy of an antimicrobial could be possible. However, a World Health Organization meeting in 1998, while stressing the need for care in the use of fluoroquinolones, did not find clear evidence of harm to man from use in animals. Nevertheless, in the US, the FDA/CVM have proposed to withdraw the use of fluoroquinolones in poultry. This proposal has been addressed very positively by industry. penicillin some drugs have retained excellent activity against particular target organisms, such as the penicillin against Streptococcus agalactia despite extensive use for 40 years. development of resistance to animal antimicrobials may present a hazard to humans when the resistant bacteria can cause disease in humans and can be transmitted via contaminated food. Bacteria from animals which do not cause human disease may still present a hazard when transferred via food if they then transfer their genetic material coding for resistance to pathogenic human bacteria. Clearly a risk to humans exists when the antimicrobial used in animals is also used in humans or displays cross resistance with an antimicrobial used in human medicine. This risk has not been quantified. lincomycin and tylosin Antibiotics of the macrolide-lincosamide group have been used in treating food animals worldwide for several decades. The most commonly used agents have been lincomycin and tylosin for controlling dysentery and Mycoplasma infections in swine and spiramycin for treating mastitis in cattle. For the past 20 years, tylosin has also been the most commonly used agent for growth promotion in swine production worldwide, whereas spiramycin has been commonly used in poultry. The use of macrolides for growth promotion has been banned in all European Union countries since July 1999. IV
  • 5. Phenylbutazone Phenylbutazone became available for use in humans for the treatment of rheumatoid arthritis and gout in (1949), but is no longer approved, and thus not marketed, for any human use in the United States. This is because some patients treated with phenylbutazone have experienced severe toxic reactions, and other effective, less toxic drugs are available to treat the same conditions. Phenylbutazone is known for its ulcerogenic, nephrotoxic, and hemotoxic effects in horses, dogs, rats, and humans. It is known to induce blood dyscrasias, including aplastic anemia, leukopenia, agranulocytosis, thrombocytopenia, and deaths. The reported adverse reactions were associated with the human clinical use of 200 to 800 milligrams phenylbutazone per day. Hypersensitivity reactions of the serum-sickness type have also been reported in patients with phenylbutazone. The threshold for this effect has not been defined. Therefore, it is unclear what level of exposure would be required to trigger such reactions in sensitive people. Moreover, phenylbutazone is a carcinogen, as determined by the National Toxicology Program (NTP) based on positive results in genotoxicity tests and some evidence of carcinogenicity seen in the rat and mouse in carcinogenicity bioassays NTP conducted. For animals, phenylbutazone is currently approved only for oral and injectable use in dogs and horses. Use in horses is limited to use in horses not intended for food. There are currently no approved uses of phenylbutazone in food-producing animals. Investigation by FDA and state regulatory counterparts has recently found phenylbutazone on farms and identified tissue residues in culled dairy cattle. In addition, the U.S. Department of Agriculture's (USDA's) Food Safety Inspection Service has reported phenylbutazone residues in culled cattle presented for slaughter for human food throughout the United States in the past 2 calendar years. This evidence indicates that the extralabel use of phenylbutazone in female dairy cattle 20 months of age or older will likely result in the presence, at slaughter, of residues that are toxic to humans, including being carcinogenic, at levels that have not been shown to be safe. Because of the likelihood of this adverse event, we are issuing an order prohibiting the extralabel use of phenylbutazone drugs in female dairy cattle 20 months of age or older. We will continue to monitor the extralabel use of phenylbutazone and will adjust the scope of this prohibition should we find that extralabel use in other species or classes of animals presents a risk to public health. V