NUTRITION                                         PIH-31

PURDUE UNIVERSITY.  COOPERATIVE EXTENSION SERVICE.
WEST LAFAYETTE, INDIANA












                      Feed Additives for Swine

Authors
Gary Parker, University of Kentucky
Gary Cromwell, University of Kentucky
Virgil Hays, University of Kentucky
James McKean, Iowa State University

Reviewers
E. T. Kornegay, Virginia Polytechnic Inst. & State Univ.
George Meyerholz, USDA, Washington, D.C.
Dean Zimmerman, Iowa State University




     Feed additives are nonnutritive  compounds  added  to  swine
diets  for the purpose of enhancing animal performance. The major
ones used in  swine  diets  are  antibiotics,  chemotherapeutics,
anthelmintics,  probiotics,  organic acids and copper sulfate. Of
these, antibiotics, chemotherapeutics, and anthelmintics are  the
major  feed  additives  used  in swine feeds and have been exten-
sively used in the United States over the last 35 years.


Antibiotics and Chemotherapeutics

     Antibiotics and chemotherapeutics are medications  added  to
swine  feeds  to  improve  health and performance. A list of com-
pounds and use levels that can be used for specific purposes such
as  growth  promotion,  prevention of disease, and treatment of a
specific disease can be found by  consulting  the  Feed  Additive
Compendium  (Miller Publishing Co, 12400 Whitewater Drive, Minne-
tonka, MN 55343, published annually). These  medications,  usages
and  levels  are  determined  by the Food and Drug Administration
(FDA). It is their  responsibility  to  determine  that  products
intended  for  animal  use are safe, effective, properly labeled,
and that food derived from treated animals is safe to eat.

     Antibiotics are compounds produced by bacteria or molds that
inhibit the growth of other microorganisms. Chemotherapeutics are
chemically synthesized compounds that inhibit the growth of  cer-
tain  microorganisms.  They  may  be used alone or in conjunction
with antibiotics for the purposes of enhancing  growth  and  feed
efficiency,  or  for  disease  control  in swine. It is generally
accepted that the beneficial effects of  these  compounds  result
from  alteration  of the bacterial population within the animal's
digestive tract. The actual mechanism by  which  antibiotics  and
chemotherapeutics  exert the growth promoting effect has remained
an elusive unknown throughout  the  35-year  history  of  feeding
these  compounds.  A number of possible mechanisms have been sug-
gested:

     (1) Metabolic Effect.  The  metabolic  effect  implies  that
antibiotics  directly  influence  the  metabolic processes in the
animal. This is not a reasonable explanation, however, for  those
antibiotics that are not absorbed from the intestinal tract.

     (2) Nutritional Effect. Certain bacteria  that  inhabit  the
intestinal  tract  synthesize  vitamins  and amino acids that are
essential to the host, while others compete with the  animal  for
essential  nutrients.  Shifts in bacterial populations due to the
feeding of antibiotics may result in a  greater  availability  of
nutrients  to  the  host  animal.  Antibiotics have been shown to
reduce the thickness of  the  intestinal  wall,  resulting  in  a
potential for greater absorption of nutrients. In addition, anti-
biotics reduce the total mass of the gut, so less  nutrients  are
wasted on these rapidly metabolized body tissues.

     (3) Disease Control Effect.  Antibiotics  tend  to  suppress
those  bacteria in the intestinal tract that cause subclinical or
nonspecific  disease.  These  subclinical  diseases  prevent  the
animal from performing to its maximum potential.

     The response to antibiotics and chemotherapeutics  seems  to
be  as  large  today  as  it  was  in earlier time periods1. Hays
(University of Kentucky, 1977) summarized many of the studies  on
the  value  of  antibiotics  in swine diets from the period 1950-
1977, and Zimmerman (Iowa State University,  1986)  surveyed  the
literature  on  the effect of antibiotics on pig performance from
the time period 1978-1985. The data in Table 1 compare the  aver-
age  percentage  improvements  resulting from antibiotic usage in
the two time periods. The percentage improvements in rate of gain
and  efficiency  of  feed  utilization  are  similar  for the two
periods. Antibiotics and chemotherapeutics remain the  most  con-
sistently  effective  feed additives for improving animal perfor-
mance.

     There are many antibiotics, chemotherapeutics, and  approved
combinations  available  for  use in swine diets. The more common
additives and their withdrawal  times  are  listed  in  Table  2.
Selection of a specific feed additive and the level necessary for
optimal response will vary depending on several factors:  1)  the
stage of growth, with response being less as the pig increases in
age; 2) disease prevalence within the herd; 3) kind of  additive;
and 4) the cleanliness and comfort of the environment.


____________________________________________________________________
|Table 1. Improvements in performance of pigs  fed  antimicrobials |
|during the years 1950-1985.                                       |
|                                                                  |
|_________________________________________________________________ |
|                                             Improvement, %       |
|                                    _____________________________ |
|  Years             Periodsa           Daily Gain       Feed/Gain |
|_________________________________________________________________ |
|1950-1977b       Starter                  16.1             6.9    |
|                 Grower-Finisher           4.0             2.1    |
|1978-1985c       Starter                  15.0             6.5    |
|                 Grower-Finisher           3.6             2.4    |
|_________________________________________________________________ |
|                                                                  |
|aStarter period from about 15 to 55 lb. and grower-finisher       |
|from 55 to 200 lb. body weight.                                   |
|bHays (1977); 15,689 pigs.                                        |
|cZimmerman (1986); 10,083 pigs.                                   |
|_________________________________________________________________ |
|Table 2. Withdrawal time for antibiotics &                        |
|chemotherapeutics in swine feeds.a                                |
|                                                                  |
|______________________________________________________________    |
|                                              Withdrawal time     |
|Chemical name                                 before slaughter    |
|______________________________________________________________    |
|Bacitracin methylene disalicylate                   none          |
|Bacitracin zinc                                     none          |
|Bambermycins                                        none          |
|Chlortetracycline                                   none          |
|Oxytetracycline                                    noneb          |
|Penicillin                                          none          |
|Tylosin                                             none          |
|Virginiamycin                                       none          |
|Apramycin                                         28 days         |
|Arsanilic acid                                     5 days         |
|Carbadox                                          70 days         |
|Chlortetracycline/sulfamethazine/penicillin       15 days         |
|Chlortetracycline/sulfathiazole/penicillin         7 days         |
|Furazolidone                                       5 days         |
|Furazolidone/oxytetracycline                       5 days         |
|Furazolidone/oxytetracycline/arsanilic acid        5 days         |
|Lincomycin                                         6 days         |
|Neomycin sulfate                                  20 days         |
|Neomycin/oxytetracycline                             c            |
|Nitrofurazone                                      5 days         |
|Tiamulin                                           2 days         |
|Tylosin/sulfamethazine                            15 days         |
|3-Nitro-4-hydroxyphenylarsonic acid                5 days         |
|______________________________________________________________    |
|                                                                  |
|aFeed Additive Compendium, 1989.                                  |
|bAt 500 g/ton use level, withdraw 5 days before slaughter.        |
|cWithdraw from feed 20 days befor slaughter  when  neomycin  base |
|level is 140 g/ton and 5 days before slaughter when neomycin base |
|__________________________________________________________________|


     Usage level of an additive or combination of additives  must
comply  with FDA approvals and the manufacturer's directions. The
FDA classifies additives into those that have a  high  degree  of
human  safety  with  no  withdrawal  time and those with a higher
potential  risk  for  edible  tissue  residue.  The  latter  have
specific  withdrawal times before slaughter2 (Table 2). Producers
must responsibly use medications in their feeding  program.  They
must  know  the approved use levels and withdrawal periods of the
compounds they use. There is no extra-label  usage  (higher  than
approved  FDA  levels or unapproved combinations) with feed addi-
tives.

     Antibiotics and chemotherapeutics are not as  commonly  used
with  breeding animals as in diets for growing pigs. Research has
shown antibiotics to be effective during certain critical  stages
of  the  reproductive  cycle,  such as at the time of breeding. A
summary of nine research trials shows that a high level  (0.5  to
1.0 gram/sow/day) of an absorbable antibiotic (such as one of the
tetracyclines) at the time of breeding improves  conception  rate
by  11%  and improves litter size by .5 pigs/litter at the subse-
quent farrowing3 (Table 3). Generally, benefit  from  antibiotics
or  chemotherapeutics  in  gestation  diets is minimal unless the
disease level within  the  herd  is  quite  high.   Antimicrobial
agents are thought to be beneficial at farrowing and during early
lactation because the sow and her pigs  are  more  vulnerable  to
stress  at  this  time.  The data in Table 4 suggest that weaning
weights are increased by about  5%  and  pig  survival  increased
slightly  when  these agents are included in the prefarrowing and
lactation diet3.


____________________________________________________________________
|                                                                  |
|Table 3. Effects of antibiotics at breeding on                    |
|reproductive performance of sows.a                                |
|                                                                  |
|_________________________________________________________________ |
|                                Control               Antibioticb |
|_________________________________________________________________ |
|Farrowing rate, %c                68.2                   79.1     |
|Live pigs/litter                   9.8                   10.3     |
|_________________________________________________________________ |
|                                                                  |
|aCromwell (1983); Data on 2,148 sows, 9 experiments, 1961-1985.   |
|bIn most cases, .5-1.0 gram/sow/day prior to and after breeding.  |
|cPercent of sows bred that farrowed.                              |
|_________________________________________________________________ |
|Table 4. Antimicrobial agents in the prefarrowing                 |
|and lactation diet for sows.a                                     |
|                                                                  |
|_________________________________________________________________ |
|                                 Control           Antimicrobialb |
|_________________________________________________________________ |
|Pigs born alive/litter             8.96                 9.13      |
|Pigs weaned/litter                 8.01                 8.25      |
|Survival, %                       89.4                 90.4       |
|Weaning weight, lb.                8.78                 9.20      |
|_________________________________________________________________ |
|                                                                  |
|aCromwell (1983); Summary of 7 experiments, 787 litters.          |
|bTetracyclines,      chlortetracycline-sulfamethazine-penicillin, |
|tylosin  or  copper  sulfate  fed from 3-5 days prepartum through |
|__________________________________________________________________|




Anthelmintics

     Swine are susceptible to infection with numerous species  of
internal   parasites  (See  PIH-44,  Internal  Parasites).  These
parasites vary widely in structure,  size,  shape,  habits,  life
cycle,  and  extent  of  injury  to  swine. The pork producer has
available a wide array of anthelmintics (dewormers) that are very
effective in controlling several parasite species.

     Some anthelmintics are more effective than others  for  cer-
tain  species  of  worms.   Producers  should become aware of the
parasite spectrum and efficacy data of each anthelmintic. Anthel-
mintics  may  be  added to swine feed for limited periods to kill
(purge)   worm    accumulation    including    worm    eggs    in
growing/finishing  swine  and  the  breeding  herd.  This type of
deworming program usually removes the immediate worm  burden  but
needs  to be repeated (time period depends on specie of worm) for
improved control. Continuous feeding of  some  anthelmintic  pro-
ducts  will  block  development of parasites during the specified
feeding period. Currently, two dewormers on the market  (pyrantel
tartrate  and  hygromycin)  can  be fed continuously in the diet.
These anthelmintics remove specific worm  parasites,  reduce  the
immediate  worm  burden  and help prevent the problem from recur-
ring. Withdrawal periods for the feed additive anthelmintics  are
listed in Table 5.


Copper Sulfate

     Elemental copper is  a  required  nutrient  for  normal  pig
growth  and is routinely added to swine diets at the rate of 6 to
11 ppm to meet this requirement.

     Copper sulfate possesses antibacterial properties and is  an
effective  growth  promotant when fed at levels of 125 to 250 ppm
of copper (1 to 2 pounds of copper sulfate/ton of  feed)  in  the
diet4,5.  The  addition of 250 ppm copper to swine diets improved
performance of weanling pigs and growing-finishing swine in  tri-
als  conducted  at the University of Kentucky (Table 6). In young
pigs, the combination of copper and antibiotics  gave  a  greater
growth  response than the feeding of copper or antibiotics alone6
(Table 7).

     Copper sulfate, when fed in excess of 250 to 500 ppm for  an
extended  period of time, may be toxic. The severity of the toxi-
city is directly related to the level fed, and  is  increased  if
the  diets are low in zinc and iron, and if the copper is fed for
a

Table 5. Withdrawal time for anthelmintics in swine feeds.a
_________________________________________________________________
                                                 Withdrawal time
Chemical name                                    before slaughter
_________________________________________________________________
Dichlorvos                                             none
Fenbendazole                                           none
Piperazine                                             none
Hygromycin B                                         15 days
Levamisole Hydrochloride                              3 days
Pyrantel Tartrate                                     1 day
Thiabendazole                                        30 days
_________________________________________________________________
a Feed Additive Compendium (1989).

Reference to products in this publication is not intended  to  be
an  endorsement  to the exclusion of others which may be similar.
Persons using such products assume responsibility for  their  use
in accordance with current directions of the manufacturer.



Table 6. Effect of copper sulfate on performance of weanling  and
growing-finishing pigs.
_________________________________________________________________
                                         Copper, ppma Improvement
_________________________________________________________________
Growth Stage                               0    250        %
_________________________________________________________________
Starting period (15 to 30 lb.)b
Daily gain, lb.                            .51   .62     21.6
Feed/gain                                 2.04  1.86      9.7
Growing period (40 to 123 lb.)c
Daily gain, lb.                           1.47  1.56      6.1
Feed/gain                                 2.80  2.70      3.7
Growing-finishing period (40 to 205 lb.)c
Daily gain, lb.                           1.56  1.63      4.2
Feed/gain                                 3.18  3.10      2.5
_________________________________________________________________
a Does not include copper in trace mineral mix.
b Cromwell et al., 1983. Summary of 12,  28-day  experiments  with
  482  pigs  weaned  at  28  days  of  age,  44 replications of 4-8
  pigs/pen, conducted at the University of Kentucky  from  1978  to
  1983.
c Cromwell  et  al.,  1981.  Summary   of   18   experiments,   84
  replications  of  four  pigs  per  treatment,  conducted  at  the
  University of Kentucky from 1970-80.



long period of time. Therefore, producers should check with their
feed  manufacturer  about  the level of copper sulfate, iron, and
zinc present in commercial feed  before  indiscriminately  adding
additional  copper  sulfate  to feed. Drawbacks to copper sulfate
supplementation include increased corrosion of  galvanized  metal
and decreased bacterial degradation of manure in lagoons.


Probiotics

     Probiotics  are  mixtures  of  bacteria,  yeasts  or   other
microorganisms  that  may  be  fed  to pigs with the intention of
establishing a population  of  desirable  microflora  within  the
intestine.  The  most common microorganisms included in probiotic
products are Lactobacillus species, Bacillus subtilis and  Strep-
tococcus  faecium  and  yeast  (Saccharomyces  cerevisiae). These
organisms, through competitive inhibition, favor the  development
of  desirable  health promoting microorganisms that theoretically
improve weight gain and feed efficiency.  To  be  effective,  the
bacteria  should  be  established  as  normal  inhabitants of the
intestinal tract of healthy animals. They must also  be  able  to
survive  passage  through the stomach and establish themselves in
the small intestine where digestion and  absorption  occur.  They
should  be  acid  and bile tolerant if they are to survive in the
digestive system.

     It has also been suggested that the  beneficial  actions  of
probiotics  include7:  (1) change the enteric flora and reduction
of E. coli; (2) synthesis of lactate with subsequent reduction in
intestinal  pH;  (3) adhesion to or colonization in the digestive
tract; (4) production of antibiotic substances; (5) reduction  of
toxic amines and ammonia levels in the gastrointestinal tract and
blood.

     There is speculation that probiotics may have some  negative
effects on pig performance, which may be caused by: nutrient com-
petition; a decrease in carbohydrate utilization; and an increase
in the transit rate of the digesta.

     Although probiotics have been commercialized and used exten-
sively  for  at  least 30 years, the documented evidence of their
therapeutic and nutritional value is still quite  variable.  Some
of  the possible reasons for the variability of results are: via-
bility of microbial cultures related to  storage  method;  strain
differences;  dose  level  and  frequency of feeding the culture;
drug  interactions;  and  lack  of  systematic  investigation  by
researchers.

     Previously,  research  information  on  probiotics  was  not
required   to  substantiate  therapeutic  or  growth  promotional
claims.  However, on June 2,  1988  FDA  published  a  compliance
statement  on direct fed microbial products. Under the new guide-
lines, a direct-fed microbial product  that  is  labeled/promoted
with any therapeutic or growth promotional claims is a new animal
drug and requires a completed new animal drug application  (NADA)
before the product can be sold with therapeutic or growth claims.
The intent of this  regulation  was  to  minimize  misleading  or
deceptive advertising for therapeutic and growth promoting claims
by microbial products in the market place.


Organic Acids

     There are several organic acid compounds available  for  use
in  feeds. Fumaric and citric acid are the most common. Both have
been shown to improve gain and feed efficiency in weanling  pigs.
The  exact mode of action is not known, but has been rationalized
from several positions:

     (1) Acidification of the diet may decrease  stomach  pH  and
increase pepsin activity (required for protein digestion).

     (2) A reduced stomach pH may decrease the  rate  of  stomach
emptying, thus increasing protein digestion time in the stomach.

     (3) A reduction in stomach pH may reduce  the  proliferation
of  coliforms  and  other pathogens in the upper gastrointestinal
tract.

     Research data have shown the effects of organic  acid  addi-
tions  to  diets on performance to be quite variable. This varia-
bility may be attributed to: 1) age of pigs;  2)  the  amount  of
milk  by-products in the diet; and, 3) the presence or absence of
antibiotics. At the present time, the optimal inclusion rate  and
economic benefits of organic acids in weanling pig diets have not
been established.


Other Additives

     Flavors are sometimes added to diets to enhance the aroma or
taste  of  the feed.  Most of the research suggests that they are
of limited benefit unless one is attempting to mask feed that has
off-odors or off-flavors.

     Enzymes are sometimes included in feeds for the  purpose  of
assisting  in the digestive process. Most research indicates very
little benefit from enzyme supplementation. An exception  is  the
enzyme, beta-glucanase, which has been shown in certain instances
to benefit the utilization of barleys  that  are  high  in  beta-
glucans,  a  complex  carbohydrate that interferes with the pig's
ability to efficiently utilize barley.

     Antioxidants are often included in feeds that  are  high  in
fat.  They  help  to prevent the feed from becoming rancid, espe-
cially in hot weather.

     Pellet binders are occasionally added by feed  manufacturers
to  feeds  prior  to  pelleting. Their purpose is to increase the
cohesiveness of the pellets.



     Proper Use of Feed Additives by Producers

     Producers should follow directions for feed  additive  usage
as  provided  by  the  manufacturer  (See  PIH-86,  Management to
Prevent Drug Residue Problems in Pork).  Thoughtful use of  these
compounds  to  maximize  profits,  while  preventing residues and
reducing consumer concern, is important.

     Antimicrobial additive claims and approved usage  levels  in
feed  are regulated by the FDA. USDA-FSIS (Food Safety Inspection
Service) is actively initiating more rigid  swine  identification
and  residue-monitoring  controls  of  pork  carcasses at packing
plants. Every pork producer must take precautions to abide by FDA
required  preslaughter  withdrawal  times  for feed additives and
other medications. To disregard these regulations could result in
a  sizable  monetary  loss to individual producers from condemna-
tions due to tissue residue and to the pork industry  from  with-
drawal of approval for certain effective feed additives.

     In using medicated  feeds  (antibiotics,  chemotherapeutics,
and anthelmintics) the producer should:

     1. Read the tag to assure that this is an appropriate  addi-
tive  for  the stage of production and is being used for approved
reasons.

     2. Comply with the proper withdrawal times to avoid residues
thereby  ensuring  safe,  wholesome pork. All approved drugs have
been tested for tissue clearance and length of withdrawal time is
based on research data and approved by regulatory agencies.

     3. Prevent drugs and medicated feed from contaminating other
medicated  or nonmedicated feeds through mixers and feed handling
equipment.

     4. Avoid giving additional medications to animals  on  medi-
cated  feed  without professional advice. One compound may inter-
fere with the effectiveness or clearance rate of another drug.

     5. Use only those medicated feeds  approved  for  swine  and
only for the appropriate purpose and stage of production.

            Table 7. Effects of  single  and  combined
            additions  of  copper  and  antibiotics on
            performance of weanling pigs.a
            ___________________________________________
                                     Additive

                           None CopperbAntibioticcBoth
            ___________________________________________
            Daily gain, lb.  .46   .57      .55     .62
            Feed/gain       1.98  1.87     1.81    1.75
            Survival, %    95   100       93      98
            ___________________________________________
            a Two trials involving 256  pigs  from  4-8
              weeks of age (15 to 30 lb.)
            b 250 ppm copper as copper sulfate.
            c 55   ppm   chlortetracycline    in    one
              experiment,  27  ppm of virginiamycin in a
              second experiment.







Summary

     The majority of feed additives available  to  producers  are
antibiotics, chemotherapeutics, anthelmintics, organic acids, and
probiotics and to a lesser extent, flavors, enzymes, antioxidants
and  pellet binders. Current research has shown that antibiotics,
chemotherapeutics and copper sulfate provide the most  consistent
improvements in growth rate and feed efficiency.

     Producers should  obtain  professional  help  to  develop  a
specific  feed  additive  program to maximize returns. Short-term
switching from one additive to another should be  avoided  unless
made in response to a new disease problem. A well planned program
can help prevent management  errors  associated  with  withdrawal
times  and  make it easier to execute specific disease prevention
and treatment programs. One should always practice good  feeding,
sanitation,  and  disease  control  management  techniques. Don't
expect to buy management in a bag of  medicated  feed.  Seek  and
utilize  the  services  of  a  practicing veterinarian and animal
nutritionist.

     Federally approved feed additives are thoroughly tested  and
proven  to  increase animal performance. Approved antibiotics and
chemotherapeutics or combinations are recommended for growth pro-
motion  in  each stage of the growth period and, for the improve-
ment of breeding and lactation performance in sows.


References:
1 Zimmerman, D. R. 1986. Role of subtherapeutic levels of  antimi-
crobials in pigs. J. Anim. Sci. 62 (Suppl. 3): 17.
2 Feed Additive Compendium, 1989.  Miller  Publishing  Co.,  12400
Whitewater Drive, Minnetonka, MN 55343.
3 Cromwell, G. L. 1983. Antibiotics for growth promotion in swine.
Animal Nutrition and Health. July/August 1983.
4 Braude, R. 1975.  Proc.  Copper  in  Farming  Symposium.  Copper
Development Association. London.
5 Cromwell, G. L., et. al. 1981. Efficacy of copper  as  a  growth
promotant  and  its interrelation with sulfur and antibiotics for
swine. Proc. Distillers Feed Conference, Cincinnati, Ohio.
6 Stahly, T.S. et.al. 1980. J. of Animal Science 51:1347.
7 Pollman, D.S. 1985. Feed ModifiersWhat Are  They?   Guelph  Pork
Symposium.
8 Hays, V. W. 1977. Effectiveness of feed additive usage of  anti-
bacterial  agents  in  swine  and  poultry  production. Office of
Technical Assessment, U.S. Congress, Washington, D.C.
9 Cromwell, G.L. et al. 1983. High levels of copper  as  a  growth
stimulant  in  starter  diets  for  weanling pigs. Kentucky Swine
Research Report No 274, 1983.





REV 4/89 (5M)  

______________________________________________

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