180.
T H E USE OF A N T I B I O T I C S 11 R U H I N A N T S
A.
-
CATTLE
Mechanics of action of a c t i b i o t i c s
An a n t i b i o t i c is a chemical compound secreted by a l i v i n g organism
which is detrimental t o the l i f e of another l i v i n g organism. These a n t i b i o t i c compounds may function as follows:
(1) Disturbing no&
chain of' events through which CIIONSP
and other metabolites a r e absorbed from the environment.
(2)
Surface a c t i v i t y (Tyrothricin) causing disruption of
s t r u c t u r a l i n t e g r i t y af' the c e l l .
The a n t i b i o t i c eubstances commonly employed i n livestock feeding
experiments exhibit a n t i b i o t i c action by meane of the first method shown.
*
A t the present time, the antibiotic8 most successrully used in
the f i e l d of livestock production are: aureomycin,terrawcin, andpenic i l l i n (poultry). Aureoqcin and terramycin are both broad spectrum antib i o t i c s being e f f e c t i v e ;tn v i t r o against many gram + and gram tyges of
organisms. Penicillin, a narrow band a n t i b i o t i c , is quite an effective
agent aga'hst gram + types of organisms. It i s in addition very low in its
toxicity as compared t o the more toxic wide band antibiotics.
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Effectiveness in vivo of ant?.biotics
The b a c t e r i a l population i n the rumen and other portions of tihe
digestive t r a c t are kmwn t o h w e an important function in the digestion of
cellulose consumed in large quantities by ruminants and i n t h e Synthesis of
certain vitamins, notable t h e B complex group. Therefore, it is imperative
that note be taken of t h s efi'ect a n t i b i o t i c s have on t h e digestive f l o r a .
Stud.ies of the e f f e c t of p e n i c i l l i n on the i n t e s t i n a l microflora
i n swine (1)ehowed that tbejce was considerable variation i n t h e number of
bacteria present wLthin treatments. Pigs fed p e n i c i l l i n (2.2 n?g. per pound
of feed) showed a significant increase i n coliform organisms. The addition
of p e n i c i l l i n t o the basal r c t i o n resulted in a highly significant correlat i o n between coliform bacteria and rates of gain. No significant correlat i o n existed between rates of gain and either Shigella, Proteus, o r Sap&lococcus count. It is possible that p e n i c i l l i n retarded t h e growth of' some
organisms which normally are antagonistic toward coliform bacteria, o r that
p e n i c i l l i n might eimply retard erne organism which normally competes with
coliform bacteria f o r aome nutrients (1).
Streptomycin (2.50 ng. per pound of feed) had but l i t t l e effect on
t h i s group. (colif o m ) 'aowever, conbinations of p e n i c i l l i n and streptomycin
had a stimulating e f f e c t on the nwllber of coliform bacteria. The inclusion
181.
of penicillin, streptomycin o r a canbination of t h e two had no significant
effect on t h e Staphylococcus genus.
When p e n i c i l l i n and streptomycin were fed singly, t h e average Proteus
counts were 68 and 72 million per gram compared t o 37 million f o r pigs fed the
basal ration. However, when coniblnations fed, there was a highly significant
increase i n the number of Proteus bacteria, 204 million per gram.
Voelker (2) subjected calves t o d i f f e r e n t treatments. (1) 30 mg,
terramycin per 100 lbs. body weight; ( 2 ) 100 mg. terramycin per 100 l b s . of body
weight; Aurofac 2.5 per cent of the grain ration. He found that there were no
significant differences in bacteria popuLation due t o a n t i b i o t i c feeding (as a
r e s u l t of bacteriological studies w i t h colon material.)
The administration t o chicks of aureomycin, bacitracin, and terramycin
a t t h e rate of 10 gram per ton of feed, and p e n i c i l l i n a t the rate of 4 grams
per ton of feed showed the following results (4). The administration of penic i l l i n , inactivated penicillin, and combination of p e n i c i l l i n and aureamycin,
and bacitracin and penicillin, produced a very signif'icant decrease i n t o t a l
number of f e c a l c l o s t r i d i a .
I n work done on chicks by Romoser, Sharp, and Cowles (5), Aerobacter
aerogenes was isolated from chick ceca and fuund t o be r e s i s t a n t t o p e n i c i l l i n
and aureomycin. Slight but consistent growth responses were obtained when
viable organisms were added t o t h e rations with o r without the a n t i b i o t i c .
Kesler (3) found that the addition of terramycin approximately 20 mg.
per 100 lb. body weight t o young calves showed no consietent differences in
thiamin levels In the rumen. The data indicates a higher l e v e l of riboflavin.
However, the addition of terramycin t o the d i e t of calves 8 10 weeks old fed
10, 20, 40 rug. terramycin/100 body veight f o r three consecutive days showed no
elevation i n riboflavin. Terraqycin then had no adverse e f f e c t on rumen synthesis. However, cellulose digestion was lover in the a n t i b i o t i c supplement
calvea. This effect seemed t o be more pronounced when terramycin wa8 administ e r & by capsule and thereby went d i r e c t l y i n t o the rumen rather than being included i n the feed.
-
The relationship between a n t i b i o t i c s and t h e l e v e l of n u t r i t i o n has
been Investigated. Antibiotics (aureomycln and p e n i c i l l i n ) were shown t o have
a greater stinrulating action with rations which are well balanced in amino acids
than with rations deficient i n some amino acid. Antibiotics do not lower the
dietary l e v e l of' protein required by the chick. I n order t o take f u l l advantage
of tbe growth stimulating properties of a n t i b i o t i c s , it is necessary t o provide
a diet of high energy and optinarm protein content as well a8 me balanced i n
a d n o 8Cid.6 ( 6 )
A broad analysis of t h e foregoing data on t h e mode of action seem t o
be best summed up by Norris (7), According t o Norris ( 7 ) "The p o s s i b i l i t y
e x i s t s t h a t a n t i b i o t i c s r e s t r i c t the growth of bacteria which destroy e s s e n t i a l
nutrient8 o r compete with the animal f o r them, and at t h e saitie time promote the
d e v e 2 a p n t of bacteria which are able t o synthesize e s s e n t i a l nutrients. Antib i o t i c s may a l s o stlmulate theee bacteria t o produce increased quantities of
essential nutrients but evidence of t h i s is lacking." Of course, there is a l -
182
.
ways the problem of the development of r e s i s t a n t straiprr of organism t o the
.
a n t i b i o t i c s which have been used, especially if administered i n insufficient
amounts
Antibiotics t o ruminants
- Calves
The e f f e c t of age on the response of rumimnts t o a n t i b i o t i c feeding
has been investigated by Perry, Beeson, Hornback, and Mohler (9), Twenty Four
mg. aureomycin/ 100 l b . l i v e weight was adininlstered d a i l y by capsule t o calves
running with dams, creep feeding and pasture available. They found scouring
seldom occurred i n the group receiving a n t i b i o t i c s , Aureomycin fed calves averaged 14.5 pounds more per calf a t 80 days than controls. Aureomycfn completely
cured a l l scouring when administered t o calves i n control lab.
-
An experiment with calves b i r t h t o 12 weeks old fed 30 mg. terramycin hydrochloride per 100 lb. body weight was conducted by YacKay, Riddell,
and Fitzsimmons (10). They noted t h a t calves of all breeds receiving terramycin made greater average daily gains than the control animals. There was no
significant difference i n feed u t i l i z a t i o n . They noted that the supplemented
calves showed more bloom and increased appetite.
Kesler (3) found t h a t calves fed terramiycin showed a greater intake
of calf starter a t an e a r l i e r age and postulates that t h i s has been a contributing f a c t o r t o increased gains.
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Calve6 s t a r t e d a t ages of 6 9 weeks were fed an average of 37.5 t o
60 xug. terramycin per head per day (10). The calves fed terramycin showed an
i n i t i a l increase Over the control c d v e s i n growth but a t the end of 8 weeks
there was l i t t l e difference noted i n rate of gain,
In the experiment by Voelker ( 2 ) calves fed 100 m@;, terramycin/100
However, the calves receiving terramycin
consumed more feed, and so did not have greater feed efficiency a s a r e s u l t .
Voelker ( 2 ) reports that no harmful effect8 were observed i n feeding 200 mg,
d a i l y of pure aureomycin plus 2,5$ aurofac i n t h e grain r a t i o n ,
lb. gained 20% more than controls.
Antibiotics t o rumiliants
-
Cattle
The foregoing data has indicated some d e f i n i t e advantage t o supplementing young calves which are not consuming large quantities of roughage
w i t h antibiotics. However, i t s application t o older ruminants which are coneuming larger quantities of r o u g w e ha8 been a matter of some question with
many workers. The follawlng survey af the l i t e r a t u r e shows some of t h e more
recent findings i n t h i s matter.
Perry, Beeson, Hornback, and Mohler (9) fed 540 l b . s t e e r s and
heifers aureomycin i n the supplement. 63.5 mg. per head the f i r s t 14 weeks,
127 mg. per head next 6 weeks, and 190.5 mg./lnead last 6 weeks. The r e s u l t s
showed t h a t the calves fed a n t i b i o t i c s gained 1.64 lb./day, controls gaining
1.52 lb./day,
The e f f e c t of a n t i b i o t i c supplement on 713 lb. yearling steers was
a l s o investigated (9). TWO l o t s were on a fattening r a t i o n and two l o t s were
on a growing ration. Each animal i n the a n t i b i o t i c l o t was given 75 mg. aureo-
183.
mycin in the supplement. !be s t e e r s fed t h e growing ration (roughages) and receiving aur&omycin grew significantly faster than controls, They showed an 185
increase in efficiency of' gain. However, of considerable interest i e t h e f a c t
that in the fattening l o t s , sureosqycin did not a f f e c t the growth end fattening
rate of s t e e r s , Both lots fed a n t i b i o t i c s s h m d a depressed appetite during
first week, but regained it rapidly, This seeme t o be characterietic of ruminants eupplemented with a n t i b i o t i c s ,
A fourth t r i a l in which increasing levels of aureoqycin were administered showed that the gradual addition of aureomycin did not give growth stimul a t i o n observed when a l e v e l of 75 mg. per steer/day war3 started.
No benefit
wa8
obtained where aureolnycin e i t h e r i n c r y e t a l l i n form o r
a8 a crude concentrate containing reei&urrlVitamin B12 was added t o a basal
fattening d i e t fed t o yearling heifers
A rather lw l e v e l was fed, 2 mg.
aureoqwin/lb. a i r dried feed, which could possibly be aasociated with such
emall response. The equality af gains of l o t receiving Vitamin 812 suggests
t h a t the a u r e q c i n destroyed or reduced B12 synthesizing organisms.
Bell, Whitehair, and Gallup (11)investigated the e f f e c t of .6 q . of
aureanrycin/day on the d i g e s t i b i l i t y of the ration of steers. (only 4 animals).
Aureomycin produced within 2 3 flays anorexia and diarrhea. "Aureomycln appeared t o decrease t h e d i g e s t i b i l i t y of dry matter an8 crude fiber 88 much 88
from 15 t o 5@.
The met pronounced effect was on d i g e s t i b i l i t y of crude f i b e r
which would suggest that aureomiycin produced an effect on the c e l l u l y t i c microorganisms in the G.I. t r a c t . It seems noteworthy here t o consider the r a t h e r
large dosege of a n t i b i o t i c as compared t o the experiment by Neunrann a t Illinois
-
(8).
In summarizing, the following conclusiane seem i n order:
The effect6 of feediag aureolqycin and terranlycin t o young calves have
resulted i n t h e followlng:
1.
Lower incidence and severity of 8cours
2.
Increased gain in weight.
3.
Better physical appearances.
The application of a n t i b i o t i c feeding t o older ruminants ha8 shown
m c h variation in e f f e c t , This seems t o be due in part t o extremes i n dosage.
However, eome workers have shown that cattle c m t o l e r a t e aureomycin and terramycin t o certain dosage l e v e l s w i t h no ill ef'f'ects.
Antibiotics seem t o funct i o n best in a growing rather than a fattening r a t i o n ,
hrt 11
The Use of Antibiotics on Preservation of Beef' Carcasses & Cut8
Weiser, Goldberg, Cahill, Kunkle, and Deatherage (12) infused rounds
and whole carc88ses from freshly killed c a t t l e with aureomycin Solution of pbys i o l o g i c a l sallne, i n which was suspended .75 g. aureomycin per 30 pound8 saline,
were forced through the a r t e r i a l system under pressure immediately after elaugh-
184.
t e r . Ten percent of t h e weight of the round was added. Controls were s e t up
with untreated and beef treated with physiological saline alone.
hours.
Carcasses were s p l i t , one side remaining a t room temperature f o r 48
The other being chilled out immediately.
No f l a v o r differences were noted from aureomycin infused carca6ses
o r rounds. Infused beef was somewhat more moist. However, decreased volume
of inf'usate and increased a n t i b i o t i c concentration showed satisfactory r e s u l t s
and reduced moisture,
Color improvement was shown on infused sides kept a t room temperature.
As would be expected, increased tenderness
at room temperature 48 hours.
WELEI
noted i n c a t t l e held
Aureomycin was shown t o be l e s s stable i n beef t i s s u e s t h n ' i n
saline at 3 O and 25OC. A t 4 days, no aureomycin was detectable i n t h e beef.
Very few organisms were present i n infused meat even i n side8 where
refrigeration m8 delayed. A l l the infused rounds were sound whereas 7 out
of 10 control rounds exhibited some off odor.
There WELEI indication that deep spoilage m y arise from organism
present i n the lymph nodes.
There was no known adverse e f f e c t by individuals consuming the beef.
Bibliography
Bridges, 3. H., Dyer, I.A., Powers, J. L., "Penicillin and streptomycin
a f f e c t the microflora of the i n t e s t i n a l t r a c t of pigs". Journal of
Animal Science. Feb. 1953 p. 96
Voelker, H e H., Casm, J, L. "Antibiotics studies with dairy calves".
Journal of Animal Science. Nov. 1951 p. 1065
Keeler, E. M. "Effect of terramycin fed t o Holstein calves on growth
i n vitro, cellulose digestion, and B vitamin synthesis". Journal of
Animal Science Vol. 13 No. 1 Feb. 1954 p. 10
Elam. "Possible mechanism involved i n growth promoting response obtained
from antibiotica". Journal of Nutrition 49:307
Romoser, G. L., Sharb, M e S., Combs, E. F. "Studies and mechanisms of
a n t i b i o t i c s in promoting chick growth". Abstract of papers presented at
41st annual meeting of Poultry Science ASEOC. Univ. of Connecticut
-
Biely, J., Mrch, B, E., Smith, D. F. "The e f f e c t of feeding a n t i b i o t i c s
on the carbohydrate and protein requirement of the chick," Poultry
Science 31 :863-870
Norris, L. C. ''What i s known about the function of antibiotics"
Froce&ings 1952 Cornell Nutrition Conference f o r Feed Mfa. New York
State College of k r i c u l t u r e Nov, 6-7, 1952 pp 62-71
185.
L., Snapp, R, R., Gall, L. So "The longtime e f f e c t of feeding
aureomycin t o fattening beef c a t t l e with bacteriological data". Jour. of
Animal Science, 10:1058
( 8 ) Neumann, A.
(9)
Perry, To W., Beeeon, Wm., Hornback, E. C,, Mohler, M, T. 11Aureomycin f o r
growing and fattening beef animls". Journal of Animal Science 13:l
p.3 1954
(10) MacKay, A. M., Riddell, W. H.,
dairy calves".
(ll) Bell, M. C.,
M t Z s h m ~ n s ,R. "Terramjrcin supplement f o r
Journal of Animal Science 1 2 : l 1953
Whitehair, C. K. Callnp-p, W, De "The effect of aureomycin on
Journal of Animal Sctence 9:647-648 1950
digestion i n steers".
(12)
Weiser, H. H., Goldberg, H, S., Cahlll, V, R. Kunkle, L. E., Deatherage,
F, E. "Observations on f r e s h meat processed by t h e infusion of antibiotics".
Food Techoloay, 1953, Vol. VII, No. 12, pp 495-499.
MR. A3AIvlS: Thank you, Bob.
that during t h e discussion.
I am sure we w i l l g e t around t o
For the next part of our program you w i l l notice we were t o have
had Shelby T. Grey, Chief, Chicago D i s t r i c t , Food and D r u g Administration,
Department of Health, Education and Welfare. He is out of town and we
have h i s very able a s s i s t a n t with us, I&.
James 1. Herring, Assis.i;&nt Chief
of t h e Chicago D i s t r i c t of the Food and Drug Administration. He i s delivering a paper prepared by Ralph F, Kneeland, who i s Assistant t o the Commissioner of the Food and D r u g Adminietration i n Washington, D. C.
(Applause )
EIR. HEZEING:
Conference.
Thbnk you, Mr. Chairman and Members of the
As Mr. ad am^^ has pointed out, I am j u s t a substitute here today
t o deliver a prepared paper f o r you,
I should l i k e t o s t a t e on behalf' of the Food and D r u g Administ r a t i o n that we do, indeed, appreciate the opportunity of appearing before
you on your program t o discuss with you very b r i e f l y some very important
points with respect t o t h e enforceinent of the Federal Food, Drug and
Cosmetic Act as it relates t o animal feeding problems. It i s always a
pleasure t o appear before groups of t h i a type, and we do especially apprec i a t e the opportunity of rtppearing before you today on t h i s very important
subject
.
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