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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 - C A T T L E

A. Mechanics of action of ac t ib io t ics

An ant ibiot ic is a chemical compound secreted by a l iving organism which is detrimental t o the l i f e of another l iving organism. b io t i c compounds may function as follows:

These ant i -

(1) Disturbing no& chain of' events through which CIIONSP and other metabolites are absorbed from the environment.

(2) Surface ac t iv i ty (Tyrothricin) causing disruption of s t ruc tura l in tegr i ty af' the ce l l .

The ant ib io t ic eubstances commonly employed in livestock feeding experiments exhibit an t ib io t ic action by meane of the first method shown.

A t the present time, the antibiotic8 most successrully used in the f ield of livestock production are: c i l l i n (poultry). b io t ics being effect ive ;tn v i t r o against many gram + and gram - tyges of organisms. agent aga'hst gram + types of organisms. toxicity as compared t o the more toxic wide band antibiotics.

aureomycin,terrawcin, andpeni- Aureoqcin and terramycin are both broad spectrum anti-

* Penicil l in, a narrow band ant ibiot ic , is quite an effective It i s in addition very low in its

Effectiveness in vivo of ant?.biotics

The bac ter ia l population i n the rumen and other portions of tihe digestive t r a c t are kmwn t o hwe an important function in the digestion of cellulose consumed in large quantit ies by ruminants and i n the Synthesis of certain vitamins, notable the B complex group. Therefore, it is imperative that note be taken of ths efi'ect ant ibiot ics have on the digestive f lora .

Stud.ies of the e f fec t of penici l l in on the in tes t ina l microflora in swine (1) ehowed that tbejce was considerable variation i n the number of bacteria present wLthin treatments. Pigs fed penici l l in (2.2 n?g. per pound of feed) showed a significant increase i n coliform organisms. The addition of penici l l in t o the basal rct ion resulted in a highly significant correla- t ion between coliform bacteria and rates of gain. t ion existed between rates of gain and either Shigella, Proteus, or Sap&- lococcus count. It is possible that penici l l in retarded the growth of' some organisms which normally are antagonistic toward coliform bacteria, or that penici l l in might eimply retard erne organism which normally competes with coliform bacteria f o r aome nutrients (1).

No significant correla-

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 penici l l in and streptomycin had a stimulating effect on the nwllber of coliform bacteria. The inclusion

181.

of penicil l in, streptomycin o r a canbination of the two had no significant effect on the Staphylococcus genus.

When penici l l in and streptomycin were fed singly, the average Proteus counts were 68 and 72 million per gram compared t o 37 million f o r pigs fed the basal ration. increase i n the number of Proteus bacteria,

However, when coniblnations fed, there was a highly significant 204 million per gram.

Voelker (2) subjected calves t o different treatments. (1) 30 mg, terramycin per 100 lbs. body weight; (2) 100 mg. terramycin per 100 lbs . 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 ant ibiot ic feeding (as a resu l t of bacteriological studies wi th colon material.)

The administration t o chicks of aureomycin, bacitracin, and terramycin a t the rate of 10 gram per ton of feed, and penici l l in a t the rate of 4 grams per ton of feed showed the following results (4). The administration of peni- c i l l i n , inactivated penicil l in, and combination of penici l l in and aureamycin, and bacitracin and penicil l in, produced a very signif'icant decrease in t o t a l number of feca l c lostr idia .

In work done on chicks by Romoser, Sharp, and Cowles (5), Aerobacter aerogenes was isolated from chick ceca and fuund t o be resis tant t o penici l l in and aureomycin. Slight but consistent growth responses were obtained when viable organisms were added t o the rations with o r without the ant ibiot ic .

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 leve l of riboflavin. However, the addition of terramycin to 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. thesis. However, cellulose digestion was lover in the ant ibiot ic supplement calvea. This effect seemed t o be more pronounced when terramycin wa8 adminis- t e r& by capsule and thereby went d i rec t ly into the rumen rather than being in- cluded i n the feed.

Terraqycin then had no adverse ef fec t on rumen syn-

The relationship between ant ibiot ics and the leve l of nutr i t ion has been Investigated. Antibiotics (aureomycln and penici l l in) 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 leve l of' protein required by the chick. I n order t o take f u l l advantage of tbe growth stimulating properties of ant ibiot ics , 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 the foregoing data on the mode of action seem t o be best summed up by Norris (7) , According t o Norris (7 ) "The possibi l i ty ex is t s t h a t ant ibiot ics r e s t r i c t the growth of bacteria which destroy essent ia l nutrient8 or compete with the animal f o r them, and at the saitie time promote the d e v e 2 a p n t of bacteria which are able t o synthesize essent ia l nutrients. b io t ics may a l s o stlmulate theee bacteria t o produce increased quantit ies of essential nutrients but evidence of t h i s is lacking."

Anti-

Of course, there is a l -

182 . ways the problem of the development of resis tant straiprr of organism t o the ant ibiot ics which have been used, especially if administered i n insufficient amounts . Antibiotics t o ruminants - Calves

has been investigated by Perry, Beeson, Hornback, and Mohler (9), mg. aureomycin/ 100 lb. l i ve weight was adininlstered dai ly by capsule t o calves running with dams, creep feeding and pasture available. seldom occurred in the group receiving ant ibiot ics , aged 14.5 pounds more per calf a t 80 days than controls. Aureomycfn completely cured a l l scouring when administered t o calves in control lab.

The effect of age on the response of rumimnts t o ant ibiot ic feeding Twenty Four

They found scouring Aureomycin fed calves aver-

An experiment with calves - b i r t h t o 12 weeks old fed 30 mg. terra- mycin hydrochloride per 100 lb. body weight was conducted by YacKay, Riddell, and Fitzsimmons (10). mycin made greater average daily gains than the control animals. significant difference i n feed ut i l izat ion. calves showed more bloom and increased appetite.

They noted t h a t calves of all breeds receiving terra- There was no

They noted that the supplemented

Kesler (3) found t h a t calves fed terramiycin showed a greater intake of calf starter at an e a r l i e r age and postulates that t h i s has been a contrib- uting factor t o increased gains.

Calve6 s tar ted a t ages of 6 - 9 weeks were fed an average of 37.5 t o 60 xug. terramycin per head per day (10). i n i t i a l increase Over the control c d v e s in growth but a t the end of 8 weeks there was l i t t l e difference noted in rate of gain,

The calves fed terramycin showed an

In the experiment by Voelker (2) calves fed 100 m@;, terramycin/100 lb. gained 20% more than controls. However, the calves receiving terramycin consumed more feed, and so did not have greater feed efficiency as a resul t . Voelker (2) reports that no harmful effect8 were observed i n feeding 200 mg, dai ly of pure aureomycin plus 2,5$ aurofac i n the grain rat ion,

Antibiotics t o rumiliants - Cattle

The foregoing data has indicated some def in i te advantage t o supple-

However, i t s application t o older ruminants which are con- menting young calves which are not consuming large quantit ies of roughage wi th antibiotics. euming larger quantit ies 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 tu re shows some of the more recent findings i n t h i s matter.

Perry, Beeson, Hornback, and Mohler (9) fed 540 lb . s teers and heifers aureomycin i n the supplement. 63.5 mg. per head the first 14 weeks, 127 mg. per head next 6 weeks, and 190.5 mg./lnead last 6 weeks. The resu l t s showed tha t the calves fed ant ibiot ics gained 1.64 lb./day, controls gaining 1.52 lb./day,

The effect of an t ib io t ic supplement on 713 lb. yearling steers was also investigated (9). on a growing ration.

TWO l o t s were on a fattening rat ion and two l o t s were Each animal i n the ant ibiot ic l o t was given 75 mg. aureo-

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mycin in the supplement. ceiving aur&omycin grew significantly faster than controls, increase in efficiency of' gain. However, of considerable interest i e the f a c t that in the fattening lo t s , sureosqycin did not affect the growth end fattening rate of s teers , Both lots fed ant ibiot ics s h m d a depressed appetite during first week, but regained it rapidly, This seeme t o be characterietic of rumi- nants eupplemented with ant ibiot ics ,

!be steers fed the growing ration (roughages) and re- They showed an 185

A fourth t r ia l in which increasing levels of aureoqycin were adminis- tered showed that the gradual addition of aureomycin did not give growth stimu- la t ion observed when a level of 75 mg. per steer/day war3 started.

No benefit wa8 obtained where aureolnycin e i ther i n cryetal l in 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 aureoqwin/lb. air dried feed, which could possibly be aasociated with such emall response. 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 effect of .6 q. of aureanrycin/day on the d iges t ib i l i t y of the ration of steers. (only 4 animals). Aureomycin produced within 2 - 3 flays anorexia and diarrhea. "Aureomycln ap- peared t o decrease the d iges t ib 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 iges t ib i l i t y of crude f i b e r which would suggest that aureomiycin produced an effect on the ce l lu ly t ic micro- organisms in the G . I . t r ac t . It seems noteworthy here t o consider the rather large dosege of ant ibiot ic as compared t o the experiment by Neunrann at Illinois

A rather lw level was fed, 2 mg.

The equality af gains of l o t receiving Vitamin 812 suggests

( 8 ) .

In summarizing, the following conclusiane seem in order:

The effect6 of feediag aureolqycin and terranlycin t o young calves have resulted in the followlng:

1. Lower incidence and severity of 8cours

2. Increased gain in weight.

3. Better physical appearances.

The application of ant ibiot ic feeding t o older ruminants ha8 shown mch variation in ef fec t , This seems t o be due in part t o extremes i n dosage. However, eome workers have shown that cattle c m to le ra te aureomycin and terra- mycin t o certain dosage levels w i t h no ill ef'f'ects. Antibiotics seem t o func- t ion best in a growing rather than a fattening ra t ion ,

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 pby- siological 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 . with untreated and beef treated with physiological saline alone.

Ten percent of the weight of the round was added. Controls were se t up

Carcasses were spli t , one side remaining at room temperature f o r 48 hours. The other being chil led out immediately.

No f lavor differences were noted from aureomycin infused carca6ses However, decreased volume or rounds. Infused beef was somewhat more moist.

of inf'usate and increased an t ib io t ic concentration showed satisfactory resu l t s and reduced moisture,

Color improvement was shown on infused sides kept at room temperature.

As would be expected, increased tenderness WELEI noted in ca t t l e held at room temperature 48 hours.

Aureomycin was shown t o be l e s s stable i n beef t issues t h n ' i n saline at 3O and 25OC. A t 4 days, no aureomycin was detectable i n the beef.

Very few organisms were present i n infused meat even i n side8 where refrigeration m8 delayed. of 10 control rounds exhibited some off odor.

A l l the infused rounds were sound whereas 7 out

There WELEI indication that deep spoilage m y arise from organism present i n the lymph nodes.

There was no known adverse effect by individuals consuming the beef.

Bibliography

Bridges, 3. H., Dyer, I.A., Powers, J. L., "Penicillin and streptomycin affect the microflora of the in tes t ina l t r a c t of pigs". Animal Science. Feb. 1953 p. 96

Voelker, H e H., Casm, J, L. Journal of Animal Science. Nov. 1951 p. 1065

Journal of

"Antibiotics studies with dairy calves".

Keeler, E. M. i n vitro, cellulose digestion, and B vitamin synthesis". Animal Science Vol. 13 No. 1 Feb. 1954 p. 10

Elam. from antibiotica". Journal of Nutrition 49:307

Romoser, G. L., Sharb, Me S., Combs, E. F. "Studies and mechanisms of ant ibiot ics 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. on the carbohydrate and protein requirement of the chick," Science 31 :863-870

Norris, L. C.

"Effect of terramycin fed t o Holstein calves on growth Journal of

"Possible mechanism involved i n growth promoting response obtained

"The effect of feeding ant ibiot ics Poultry

''What i s known about the function of antibiotics" Froce&ings 1952 Cornell Nutrition Conference f o r Feed Mfa. State College of k r i c u l t u r e Nov, 6-7, 1952 pp 62-71

New York

185.

( 8 ) Neumann, A. L., Snapp, R, R., Gall, L. So aureomycin t o fattening beef ca t t l e with bacteriological data". Animal Science, 10:1058

"The longtime effect of feeding Jour. of

(9) Perry, To W., Beeeon, Wm., Hornback, E. C,, Mohler, M, T. 11 Aureomycin f o r

p.3 1954 growing and fattening beef animls". Journal of Animal Science 13:l

(10) MacKay, A. M., Riddell, W. H., MtZshm~ns , R. dairy calves". Journal of Animal Science 12 : l 1953

(ll) Bell, M. C., Whitehair, C. K. Callnp-p, W, De digestion i n steers". Journal of Animal Sctence 9:647-648 1950

(12) Weiser, H. H., Goldberg, H, S., Cahlll, V, R. Kunkle, L. E., Deatherage, F, E. "Observations on f resh meat processed by the infusion of antibiotics". Food Techoloay, 1953, Vol. VII, No. 12, pp 495-499.

"Terramjrcin supplement f o r

"The effect of aureomycin on

MR. A3AIvlS: Thank you, Bob. I am sure we w i l l ge t around t o that during t h e discussion.

For the next part of our program you w i l l notice we were t o have had Shelby T. Grey, Chief, Chicago Distr ic t , Food and D r u g Administration, Department of Health, Education and Welfare. have h is very able assis tant with us, I&. James 1. Herring, Assis.i;&nt Chief of t h e Chicago Dis t r ic t of the Food and Drug Administration. ing a paper prepared by Ralph F, Kneeland, who i s Assistant t o the Com- missioner of the Food and D r u g Adminietration i n Washington, D. C. (Applause )

He is out of town and we

He i s deliver-

EIR. HEZEING: Thbnk you, Mr. Chairman and Members of the Conference.

As Mr. ad am^^ has pointed out, I am j u s t a substi tute here today t o deliver a prepared paper f o r you,

I should l ike t o s t a t e on behalf' of the Food and D r u g Adminis- t r a t ion that we do, indeed, appreciate the opportunity of appearing before you on your program t o discuss with you very br ie f ly some very important points with respect t o the enforceinent of the Federal Food, Drug and Cosmetic Act as it relates t o animal feeding problems. pleasure t o appear before groups of thia type, and we do especially appre- c ia te the opportunity of rtppearing before you today on t h i s very important subject .

It i s always a

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