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Studies on the Stimulation of Growth by Dietary Antibiotics
Studies on the Stimulation of Growth by Dietary Antibiotics 1. CHANGES IN GROWTH RESPONSE OF CHICKS TO ANTIBIOTICS OVER A THREE YEAR PERIOD 1 F. E. NELSON, L. S. JENSEN AND J. MCGINNIS Department of Poultry Science, Washington State University, Pullman (Received for publication December 26, 1962)
NTIBIOTICS have been shown to •• have their greatest effect on growth of chicks reared in an old environment (Coates et al., 1951; Hill et al., 1953; and others). Nevertheless, Waibel et al. (1954) and Libby and Schaible (1955) reported that the continued feeding of antibiotics in a given environment resulted in a gradually decreased growth response. McGinnis et al. (1958) reported that new antibiotics (not previously used in feeds) stimulated growth, whereas antibiotics used for some time in feeds did not. Heth and Bird (1962) found no difference in growth response when antibiotics were fed over an extended period. Penicillin had been used routinely in diets fed in our laboratory since 1950. The growth response to this antibiotic was small, but antibiotics not previously used, such as bacitracin and erythromycin, gave a pronounced response. Therefore, the following summary of experiments over a 3-year period using these antibiotics was made in an attempt to demonstrate the effect of long-time usage of antibiotics in the same environment on growth stimulation. PROCEDURE
The percentage growth response obtained from penicillin, bacitracin, ery1 Scientific Paper No. 2269, Washington Agricultural Experiment Stations, Pullman. Project No. 1057.
thromycin, and tylosin was summarized from 29 experiments which were conducted over a 3-year period. The results of experiments conducted within a 4month period were averaged together. Penicillin was used routinely in the laboratory before and during the entire period. Erythromycin was used extensively in experimental studies during the last third of 1958 and first third of 1959, and then fed only once every four months until the fall of 1960. Bacitracin was used regularly in the experiments from the middle of 1959 through the remainder of the experimental period. It was also used in some routine nutritional studies during this period. Tylosin was first fed during November, 1959, and was then fed in each experiment for the next 16 months. Either day-old Single Comb White Leghorn, Delaware X New Hampshire, or White Olympian chicks were used in the experiments. In all experiments the chicks were maintained in conventional electrically-heated, wire-floored batteries in an air conditioned room. The experiments were terminated when the chicks were 3 or 4 weeks old. Feed and water were available ad libitum. Composition of the basal diets is shown in Table 1. Diet 1 was fed from 1958 through 1960 and Diet 2 in 1961. Pencillin was used at a level of 4, 10, and 20 grams per ton, erythromycin at 4, 20, and 40 grams per ton, and bacitracin and tylosin at 10 and 20 grams
906
Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on February 28, 2015
A
907
ANTIBIOTICS G R O W T H R E S P O N S E
per ton. A total of 1,090 chicks was fed penicillin, 720 chicks erythromycin, 1,030 chicks bacitracin, and 600 chicks tylosin. The chicks were in groups of ten birds, except for three experiments where they were in groups of 30 birds. RESULTS AND DISCUSSION
i":
1
^Hl
o
rr o 2 0 J3
Diet 2
%
/o 61.0 26.0 5.0
59.0 Corn (yellow) 26.0 Soybean oil meal (50% protein) 5.0 Fish meal (herring) 3.0 Tallow 2.5 Dehydrated alfalfa meal (17% protein) 1.5 Calcium carbonate Dicalcium phosphate (DynaPhos) 1.5 0.5 Salt (iodized) Corn oil — Premix 1.0'
—
2..S
1.5 1.5 0.5 1.0 1.0
The development of organisms resistant to antibiotics was shown by Smith and Crabb (1957). They reported that a higher proportion of tetracycline-resistant Bacterium"coli (or E. coli) was found in
Penicillin
Bacitracin I
Tylosin
<£ o
•-
^
o
^_
15
2-1958
3-'58
|-'59
2-'59 Periods
b
a Supplied the following per kg. of diet: vitamin A, 1,320 I.U.; vitamin Dj, 600 I.C.U.; choline chloride, 880 mg.; riboflavin, 1.36 mg.; pantothenic acid, 2.2 mg.; niacin, 6.6 mg.; manganese sulfate, 500 mg.; and sulfaquino.xaline, 925 mg. b Supplied the following per kg. of diet: vitamin A, 2,640 I.U.; vitamin D3, 704 I.CU.J thiamine, 1.76 mg.; riboflavin, 2.86 mg.; biotin, 0.888 mg.; pantothenic acid, 9.24 mg.; choline chloride, 1,320 mg.; folic acid, 0.55 mg.; ethoxyquin, 125 mg.; and manganese sulfate, 400 mg.
Erythromycin
B H I
Diet 1
Ingredients
3-'59 (4 month
l-'60
2-'60
3-'60
1 -'61
interval)
FIG. 1. Pattern of chick growth response to specific antibiotics over a period of three years.
Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on February 28, 2015
A summary of the experiments is presented in Figure 1. All the antibiotics stimulated growth although the increase in growth rate was slight in some cases. A consistently greater response was obtained from the newer antibiotics when they were first fed, or if fed only occasionally, while penicillin gave only a small response during the period. I t appears t h a t through continuous feeding of an antibiotic, the microflora of the intestine which depress growth became resistant to the drug. Further evidence for this is the decreased response to bacitracin as it was used routinely in the laboratory. Tylosin also showed a gradual decrease in growth stimulation after its initial use in the laboratory.
TABLE 1.—Composition of basal diets
908
F. E. N E L S O N , L. S. J E N S E N AND J.
The results of these experiments support the contention of McGinnis et al. (1958) that strains of microorganisms, against which antibiotics act to permit greater growth of animals, developed resistance to routinely used antibiotics. On the other hand, the results disagree with Libby and Schaible (1955) and Waibel et al. (1954), who suggested t h a t the continuous use of antibiotics over a long period produced an environment with a lowered germ load or disease potential, which allowed a greater growth of the birds not receiving antibiotics. However, Heth and Bird (1962) concluded after summarizing experiments over a 10-year period t h a t there were no long-term changes in weight responses due to feeding antibiotics. Waibel et al. (1960) reported that antibiotics used during a prolonged period were less effective in promoting growth than the new antibiotics and they suggested that the new antibiotics may suffer similar consequences after a period of use.
The results presented here indicate t h a t the newer antibiotics lose their effectiveness in promoting growth when fed for some time in the same environment. These data suggest that routine switching of antibiotics may be necessary to obtain a consistent growth response. SUMMARY
The percentage growth response obtained from feeding penicillin, bacitracin, erythromycin, and tylosin in the same environment was summarized from 29 experiments conducted over 3 years. Consistently greater growth response was obtained with antibiotics when they were first used, or used only occasionally. When bacitracin was fed routinely, the growth response to this antibiotic decreased gradually over an 18-month period. Penicillin, which had been used in the environment both prior to and during the tests, gave only a small growth response throughout the period. Tylosin stimulated growth markedly when first used, but the response diminished with subsequent use. Erythromycin stimulated growth when used only occasionally, but the response decreased when it was used routinely.
REFERENCES Coates, M. E., C. D. Dickinson, G. F. Harrison and S. K. Kon, 1951. The effect of antibiotics on the growth of chicks deprived of vitamins of the B complex. Biochem. J. 49: lxvii-lxix. Domermuth, C. H., 1960. Antibiotic resistance and mutation rates of mycoplasma. Avian Dis. 4: 456-462. Heth, D. A., and H. R. Bird, 1962. Growth response of chicks to antibiotics from 1950 to 1961. Poultry Sci. 41: 755-760. Hill, D. C , H. D. Branion and S. J. Slinger, 1953. Influence of environment on the growth response of chicks to penicillin. Poultry Sci. 31: 920. Libby, D. A., and P. J. Schaible, 1955. Observations on growth responses to antibiotics and arsenic acids in poultry feeds. Science 121: 733-734.
Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on February 28, 2015
the feces of pigs and chickens t h a t had been fed diets containing low levels of tetracyclines t h a n was found in the feces of pigs and chickens kept on farms where tetracyclines were not fed. The number of resistant organisms increased with continued feeding of tetracyclines. Domermuth (1960) reported that the feeding of low levels of streptomycin and erythromycin led to mutation and to consequent development of resistant strains of M. gallisepticum ( P P L O ) . Lowbury (1960) reviewed the literature on drug-resistant pathogens and pointed out t h a t the longtime use of penicillin, erythromycin, tetracyclines, streptomycin, and chloramphenical in hospitals or by patients resulted in an increase of resistant strains. However, recently discovered antibiotics have been able to control some of the resistant strains which have developed.
MCGINNIS
ANTIBIOTICS GROWTH RESPONSE Lowbury, E. J. L., 1960. Clinical problems of drugresistant pathogens. Brit. Med. Bull. 16: 73-78. McGinnis, J., L. H. Merrill, R. E. Fry and L. S. Jensen, 1958. Use-history of antibiotics as related to their efficacy in promoting growth of turkeys. Poultry Sci. 37: 810-813. Smith, H. W., and W. E. Crabb, 1957. The effect of continuous administration of diets containing low levels of tetracyclines on the incidence of drug resistant Bacterium coli in the feces of pigs and
909
chickens: the sensitivity of Bact. coli to other chemotherapeutic agents. Vet. Record, 69: 2430. Waibel, P. E., O. J. Abbott, C. A. Bowman and H. R. Bird, 1954. Disappearance of growth response of chicks to dietary antibiotics in an "old" environment. Poultry Sci. 33: 1141-1146. Waibel, P. E., E. L. Johnson and J. W. Hassing, 1960. Comparison of various dietary antibiotics for turkey poults. Poultry Sci. 39:611-613.
2. EFFECT OF ANTIBIOTICS ON METABOLIZABLE ENERGY OF THE DIET 1 F. E. NELSON, L. S. JENSEN AND J. MCGINNIS Department of Poultry Science, Washington State University, Pullman (Received for publication December 26,1962)
I
MPROVEMENT in the utilization of protein and of certain vitamins and minerals are associated with the feeding of antibiotics to poultry and swine (Jukes, 1955). However, the effect of antibiotics on energy metabolism has not been thoroughly investigated. Sibbald et al. (1961) and Slinger et al. (1962) concluded that antibiotics had little or no effect on metabolizable energy (ME) of feeds fed to turkeys. On the other hand, Gorril et al. (1960) reported an increased energy digestibility coefficient in swine that had responded in growth to antibiotic feeding, and Abraham et al. (1958) concluded that antibiotics spare energy during antibiotic growth stimulation of rats. The experiments reported here were conducted to study the effect of antibiotics on chick growth, feed efficiency and ME of a practical chick diet. 1 Scientific Paper No. 2271, Washington Agricultural Experiment Stations, Pullman. Project 1057.
EXPERIMENTAL PROCEDURE
Day-old Delaware X New Hampshire crossbred chicks were randomly distributed into groups of five male and five female chicks each. Three groups were fed each experimental diet in experiment 1, and five groups in experiment 2. They were maintained in conventional electrically-heated, wire-floored batteries in an air conditioned room. Feed and water were available ad libitum. Composition of the basal diet is presented in Table 1. Chromic oxide was added to each diet at 3 weeks at a level of 0.03%. Several different antibiotics were used (Table 2 and 3). Growth response to antibiotics in our laboratory had been erratic before these experiments were conducted, so 2% fresh hen excreta were added to some of the diets in experiment 1 and to all the diets in experiment 2, in an attempt to insure a growth response to antibiotics. The excreta was obtained from caged laying hens, diluted with water, mixed in a
Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on February 28, 2015
Studies on the Stimulation of Growth by Dietary Antibiotics
NTIBIOTICS have been shown to •• have their greatest effect on growth of chicks reared in an old environment (Coates et al., 1951; Hill et al., 1953; and others). Nevertheless, Waibel et al. (1954) and Libby and Schaible (1955) reported that the continued feeding of antibiotics in a given environment resulted in a gradually decreased growth response. McGinnis et al. (1958) reported that new antibiotics (not previously used in feeds) stimulated growth, whereas antibiotics used for some time in feeds did not. Heth and Bird (1962) found no difference in growth response when antibiotics were fed over an extended period. Penicillin had been used routinely in diets fed in our laboratory since 1950. The growth response to this antibiotic was small, but antibiotics not previously used, such as bacitracin and erythromycin, gave a pronounced response. Therefore, the following summary of experiments over a 3-year period using these antibiotics was made in an attempt to demonstrate the effect of long-time usage of antibiotics in the same environment on growth stimulation. PROCEDURE
The percentage growth response obtained from penicillin, bacitracin, ery1 Scientific Paper No. 2269, Washington Agricultural Experiment Stations, Pullman. Project No. 1057.
thromycin, and tylosin was summarized from 29 experiments which were conducted over a 3-year period. The results of experiments conducted within a 4month period were averaged together. Penicillin was used routinely in the laboratory before and during the entire period. Erythromycin was used extensively in experimental studies during the last third of 1958 and first third of 1959, and then fed only once every four months until the fall of 1960. Bacitracin was used regularly in the experiments from the middle of 1959 through the remainder of the experimental period. It was also used in some routine nutritional studies during this period. Tylosin was first fed during November, 1959, and was then fed in each experiment for the next 16 months. Either day-old Single Comb White Leghorn, Delaware X New Hampshire, or White Olympian chicks were used in the experiments. In all experiments the chicks were maintained in conventional electrically-heated, wire-floored batteries in an air conditioned room. The experiments were terminated when the chicks were 3 or 4 weeks old. Feed and water were available ad libitum. Composition of the basal diets is shown in Table 1. Diet 1 was fed from 1958 through 1960 and Diet 2 in 1961. Pencillin was used at a level of 4, 10, and 20 grams per ton, erythromycin at 4, 20, and 40 grams per ton, and bacitracin and tylosin at 10 and 20 grams
906
Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on February 28, 2015
A
907
ANTIBIOTICS G R O W T H R E S P O N S E
per ton. A total of 1,090 chicks was fed penicillin, 720 chicks erythromycin, 1,030 chicks bacitracin, and 600 chicks tylosin. The chicks were in groups of ten birds, except for three experiments where they were in groups of 30 birds. RESULTS AND DISCUSSION
i":
1
^Hl
o
rr o 2 0 J3
Diet 2
%
/o 61.0 26.0 5.0
59.0 Corn (yellow) 26.0 Soybean oil meal (50% protein) 5.0 Fish meal (herring) 3.0 Tallow 2.5 Dehydrated alfalfa meal (17% protein) 1.5 Calcium carbonate Dicalcium phosphate (DynaPhos) 1.5 0.5 Salt (iodized) Corn oil — Premix 1.0'
—
2..S
1.5 1.5 0.5 1.0 1.0
The development of organisms resistant to antibiotics was shown by Smith and Crabb (1957). They reported that a higher proportion of tetracycline-resistant Bacterium"coli (or E. coli) was found in
Penicillin
Bacitracin I
Tylosin
<£ o
•-
^
o
^_
15
2-1958
3-'58
|-'59
2-'59 Periods
b
a Supplied the following per kg. of diet: vitamin A, 1,320 I.U.; vitamin Dj, 600 I.C.U.; choline chloride, 880 mg.; riboflavin, 1.36 mg.; pantothenic acid, 2.2 mg.; niacin, 6.6 mg.; manganese sulfate, 500 mg.; and sulfaquino.xaline, 925 mg. b Supplied the following per kg. of diet: vitamin A, 2,640 I.U.; vitamin D3, 704 I.CU.J thiamine, 1.76 mg.; riboflavin, 2.86 mg.; biotin, 0.888 mg.; pantothenic acid, 9.24 mg.; choline chloride, 1,320 mg.; folic acid, 0.55 mg.; ethoxyquin, 125 mg.; and manganese sulfate, 400 mg.
Erythromycin
B H I
Diet 1
Ingredients
3-'59 (4 month
l-'60
2-'60
3-'60
1 -'61
interval)
FIG. 1. Pattern of chick growth response to specific antibiotics over a period of three years.
Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on February 28, 2015
A summary of the experiments is presented in Figure 1. All the antibiotics stimulated growth although the increase in growth rate was slight in some cases. A consistently greater response was obtained from the newer antibiotics when they were first fed, or if fed only occasionally, while penicillin gave only a small response during the period. I t appears t h a t through continuous feeding of an antibiotic, the microflora of the intestine which depress growth became resistant to the drug. Further evidence for this is the decreased response to bacitracin as it was used routinely in the laboratory. Tylosin also showed a gradual decrease in growth stimulation after its initial use in the laboratory.
TABLE 1.—Composition of basal diets
908
F. E. N E L S O N , L. S. J E N S E N AND J.
The results of these experiments support the contention of McGinnis et al. (1958) that strains of microorganisms, against which antibiotics act to permit greater growth of animals, developed resistance to routinely used antibiotics. On the other hand, the results disagree with Libby and Schaible (1955) and Waibel et al. (1954), who suggested t h a t the continuous use of antibiotics over a long period produced an environment with a lowered germ load or disease potential, which allowed a greater growth of the birds not receiving antibiotics. However, Heth and Bird (1962) concluded after summarizing experiments over a 10-year period t h a t there were no long-term changes in weight responses due to feeding antibiotics. Waibel et al. (1960) reported that antibiotics used during a prolonged period were less effective in promoting growth than the new antibiotics and they suggested that the new antibiotics may suffer similar consequences after a period of use.
The results presented here indicate t h a t the newer antibiotics lose their effectiveness in promoting growth when fed for some time in the same environment. These data suggest that routine switching of antibiotics may be necessary to obtain a consistent growth response. SUMMARY
The percentage growth response obtained from feeding penicillin, bacitracin, erythromycin, and tylosin in the same environment was summarized from 29 experiments conducted over 3 years. Consistently greater growth response was obtained with antibiotics when they were first used, or used only occasionally. When bacitracin was fed routinely, the growth response to this antibiotic decreased gradually over an 18-month period. Penicillin, which had been used in the environment both prior to and during the tests, gave only a small growth response throughout the period. Tylosin stimulated growth markedly when first used, but the response diminished with subsequent use. Erythromycin stimulated growth when used only occasionally, but the response decreased when it was used routinely.
REFERENCES Coates, M. E., C. D. Dickinson, G. F. Harrison and S. K. Kon, 1951. The effect of antibiotics on the growth of chicks deprived of vitamins of the B complex. Biochem. J. 49: lxvii-lxix. Domermuth, C. H., 1960. Antibiotic resistance and mutation rates of mycoplasma. Avian Dis. 4: 456-462. Heth, D. A., and H. R. Bird, 1962. Growth response of chicks to antibiotics from 1950 to 1961. Poultry Sci. 41: 755-760. Hill, D. C , H. D. Branion and S. J. Slinger, 1953. Influence of environment on the growth response of chicks to penicillin. Poultry Sci. 31: 920. Libby, D. A., and P. J. Schaible, 1955. Observations on growth responses to antibiotics and arsenic acids in poultry feeds. Science 121: 733-734.
Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on February 28, 2015
the feces of pigs and chickens t h a t had been fed diets containing low levels of tetracyclines t h a n was found in the feces of pigs and chickens kept on farms where tetracyclines were not fed. The number of resistant organisms increased with continued feeding of tetracyclines. Domermuth (1960) reported that the feeding of low levels of streptomycin and erythromycin led to mutation and to consequent development of resistant strains of M. gallisepticum ( P P L O ) . Lowbury (1960) reviewed the literature on drug-resistant pathogens and pointed out t h a t the longtime use of penicillin, erythromycin, tetracyclines, streptomycin, and chloramphenical in hospitals or by patients resulted in an increase of resistant strains. However, recently discovered antibiotics have been able to control some of the resistant strains which have developed.
MCGINNIS
ANTIBIOTICS GROWTH RESPONSE Lowbury, E. J. L., 1960. Clinical problems of drugresistant pathogens. Brit. Med. Bull. 16: 73-78. McGinnis, J., L. H. Merrill, R. E. Fry and L. S. Jensen, 1958. Use-history of antibiotics as related to their efficacy in promoting growth of turkeys. Poultry Sci. 37: 810-813. Smith, H. W., and W. E. Crabb, 1957. The effect of continuous administration of diets containing low levels of tetracyclines on the incidence of drug resistant Bacterium coli in the feces of pigs and
909
chickens: the sensitivity of Bact. coli to other chemotherapeutic agents. Vet. Record, 69: 2430. Waibel, P. E., O. J. Abbott, C. A. Bowman and H. R. Bird, 1954. Disappearance of growth response of chicks to dietary antibiotics in an "old" environment. Poultry Sci. 33: 1141-1146. Waibel, P. E., E. L. Johnson and J. W. Hassing, 1960. Comparison of various dietary antibiotics for turkey poults. Poultry Sci. 39:611-613.
2. EFFECT OF ANTIBIOTICS ON METABOLIZABLE ENERGY OF THE DIET 1 F. E. NELSON, L. S. JENSEN AND J. MCGINNIS Department of Poultry Science, Washington State University, Pullman (Received for publication December 26,1962)
I
MPROVEMENT in the utilization of protein and of certain vitamins and minerals are associated with the feeding of antibiotics to poultry and swine (Jukes, 1955). However, the effect of antibiotics on energy metabolism has not been thoroughly investigated. Sibbald et al. (1961) and Slinger et al. (1962) concluded that antibiotics had little or no effect on metabolizable energy (ME) of feeds fed to turkeys. On the other hand, Gorril et al. (1960) reported an increased energy digestibility coefficient in swine that had responded in growth to antibiotic feeding, and Abraham et al. (1958) concluded that antibiotics spare energy during antibiotic growth stimulation of rats. The experiments reported here were conducted to study the effect of antibiotics on chick growth, feed efficiency and ME of a practical chick diet. 1 Scientific Paper No. 2271, Washington Agricultural Experiment Stations, Pullman. Project 1057.
EXPERIMENTAL PROCEDURE
Day-old Delaware X New Hampshire crossbred chicks were randomly distributed into groups of five male and five female chicks each. Three groups were fed each experimental diet in experiment 1, and five groups in experiment 2. They were maintained in conventional electrically-heated, wire-floored batteries in an air conditioned room. Feed and water were available ad libitum. Composition of the basal diet is presented in Table 1. Chromic oxide was added to each diet at 3 weeks at a level of 0.03%. Several different antibiotics were used (Table 2 and 3). Growth response to antibiotics in our laboratory had been erratic before these experiments were conducted, so 2% fresh hen excreta were added to some of the diets in experiment 1 and to all the diets in experiment 2, in an attempt to insure a growth response to antibiotics. The excreta was obtained from caged laying hens, diluted with water, mixed in a
Downloaded from http://ps.oxfordjournals.org/ at Michigan State University on February 28, 2015
Studies on the Stimulation of Growth by Dietary Antibiotics