- Email: [email protected]
Studies of Nutritional Levels of Oleandomycin in Broiler Rations
Studies of Nutritional Levels of Oleandomycin in Broiler Rations W. C. SHERMAN, G. A. DONOVAN, W. M. REYNOLDS AND H. G. LUTHER Agricultural Research Center, Chas. Pfizer &• Co., Inc., Terre Haute, Indiana (Received for publication January 13, 19S9)
sponses to antibiotics in their laboratory had decreased from 19 percent in 1950 to 3.3 percent in 1953 during which period the growth of the negative controls had steadily improved so that in 1953 the growth without antibiotics was 19 percent better than in 1950. They likewise suggested that the environmental germ load or disease potential had been lowered by the continuous use of antibiotics. This interpretation is further supported by the failure to obtain significant antibiotic responses in chicks under germ-free conditions by Gordon (1952) or in a "new" environment not previously used in chick rearing (Coates et al., 1951; Hill et al., 1953; and Lillie et al., 1953). Under our laboratory conditions where antibiotics have been fed in most experiments, chick responses to penicillin are variable and in recent years have been relatively small. Early chick trials with a new antibiotic oleandomycin* (Sherman et al., 1957) indicated that sizable growth responses could be obtained with nutritional levels of this antibiotic under conditions where penicillin responses were relatively small. Outstanding oleandomycin responses in turkey poults fed synthetic rations were reported by Supplee et al. (1958) and with practical rations, oleandomycin produced several times the growth increment obtained with penicillin (McGinnis et al., 1958). It is the purpose of this paper to present data from addi* Trademark of Chas. Pfizer & Co., Inc. for oleandomycin is Matromycin.
869
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
I
N EARLY nutrition studies with antibiotics in chicks (Matterson and Singsen, 1951; Heuser and Norris, 1952; and Lillie and Bird, 1952), consistent and relatively large growth responses were obtained in the range of 10 to 20 percent. Similarly with turkey poults, reports of early experiments by Stokstad and Jukes (1950), Almquist and Merritt (1951), Branion and Hill (1951), McGinnis et al. (1951) and Williams and Hill (1952) showed growth responses to antibiotics of 20 percent to over 40 percent. Under conditions of continuous feeding of antibiotics with relatively good sanitation some investigators have observed that in recent years the percentage response to antibiotics has decreased. This diminished antibiotic response has been associated with a pronounced improvement with time in the performance of the non-supplemented control groups rather than a decreased growth rate of the antibiotic-supplemented groups. Waibel et al. (1954) reported results of antibiotic trials conducted in an "old" environment during the years 1950, '51, '52 and '53 during which period the antibiotic response steadily decreased and it was observed that the antibiotic response was large when the growth of the control groups was poor, and small with goodgrowing control groups. The authors concluded that possibly the harmful bacteria of the environment had been eliminated through the continuous use of antibiotics. Libby and Schaible (1955) reported that during these same years chick growth re-
870
W. C. SHERMAN, G. A. DONOVAN, W. M. REYNOLDS AND H. G. LUTHER
tional chick trials to evaluate oleandomycin at lower levels, and to investigate combinations of this antibiotic with penicillin under battery conditions and under practical conditions of floor-pen operation. EXPERIMENTAL
RESULTS
Experiments 1, 2 and 3. Growth and
TABLE 1.—Composition of basal diets 5
4 Experiment N o .
1
2 &3 0-5 wks.
Ground yellow corn Soybean oil meal ( 5 1 % protein) Soybean oil meal (44% protein) Corn gluten meal Corn oil Stabilized animal fat Fish meal (Menhaden, 6 0 % protein) Dried distillers solubles Dried whey-product (50% lactose) Dried brewers yeast Dehydrated alfalfa (17% protein) CaCOj Dicalcium phosphate Na 2 HP04 Salt, iodized Mineral mix a BHTb DL-Methionine Vigofac c Nicarbazin (coccidiostat) Vitamin mix l d Vitamin mix 2 Vitamin mix 3 Protein Prod, energy Cal./lb. Cal. /protein
50.78 38.15
56.45
— — 6.10 — — — — — — 1.40
26.94 2.50
1.35 0.46 0.61 0.10 0.0125 0.14 0.30
—
— 1.50 4.00 1.00 1.00 1.50 2.00 1.30 1.00
— 0.40 0.10
— 0.60 — —
— — — — 0.30 —
24.00 1,008.00 42.00
22.16 929.00 42.00
0.01
6-9 wks.
0-5 wks.
6-10 wks. 62.83 18.42
51.07 38.15
66.15 27.68
49.15 28.65
— — 6.10 — — — — — — 1.40
— — 1.49 — — — — — — 1.40
— 2.50 — 5.98
—
4.00 1.00 1.00 1.50 2.00 1.23 1.67
4.00 1.00 1.00 1.50 2.00 1.23 1.67
— 0.50
— 0.50
0.10 0.0125 0.10
0.10 0.0125 0.10
— 0.0125 — — 0.60
— 0.0125 — — 0.60
1.35 0.46 0.61 0.10 0.0125 0.14
— 0.0125
1.35 0.46 0.61 0.10 0.0125 0.14
—
0.60
0.0125 0.60
— —
— —
24.00 1,008.00 42.00
20.00 980.00 49.00
24.00 1,008.00 42.00
•
2.50
— 2.53
20.00 1,000.00 50.00
* Mineral mix contained the following percentages: Ca 27.0, M n 6.0, F e 2 . 0 , 1 0.12, Cu 0.20, Co 0.02 a n d Zn 0.006%. Butylated hydroxytoluene, antioxidant. ° Trademark of Chas. Pfizer & Co., Inc. for fermentation source of unidentified growth factors. d Vitamin mix 1 supplied the following per lb. of ration: vitamin A, 4,500 U.S.P. units; vitamin D3, 680 I.C. units; vitamin B12; 12.5 meg.; niacin, 12 mg.; choline chloride, 230 mg.; riboflavin, 2.5 mg.; pantothenic acid, 5 mg.; pyridoxine, 3 rag.; vitamin E ; 100 I.U.; and menadione bisulfite, 1.4 mg. Vitamin mix 2 supplied the following per lb. of ration: vitamin A, 2,250 U.S.P. u n i t s ; vitamin D3, 340 I.C. units; vitamin B12, 20 meg.; niacin, 5 mg.; cholune chloride, 180 mg.; riboflavin, 2.4 mg.; and pantothenic acid, 2.5 mg. Vitamin mix 3 supplied the following per lb. of ration: vitamin A, 2,250 U.S.P. units; vitamin D3, 680 I.C. units; vitamin Bis, 12.5 meg.; niacin, 12 mg.; choline chloride, 230 mg.; riboflavin, 2.4 mg.; pantothenic acid, 4 mg.; and vitamin E, 100 I.U.
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
Three starting chick and two practical broiler experiments were conducted. Nichol's Lancaster White Cross chicks were used in all experiments except experiment 5 in which the birds were Thompson White Rock strain. In experiments 1, 2 and 3 the day-old chicks were raised to 4 weeks of age in wire-floored electrically heated batteries. Quadruplicate groups of 10 chicks (5 males and 5 females) were fed the basal diets given in Table 1, supplemented as shown in succeeding tables. In experiments 4 and 5, birds were raised to 9 and 10 weeks respectively in 8'X12' floor pens with 25 males and 25 females
randomly placed in each pen. The negative controls were run in quadruplicate and each treatment in duplicate. Pens were assigned to each treatment under a system of restricted randomization to permit evaluations of pen location effect. The starting basal diets, shown in Table 1, were fed to 4 weeks in the battery trials and to 5 weeks in the floor pen trials; the finishers were fed for the remainder of the floor pen experiments. The treatment groups were supplemented with crystalline oleandomycin or procaine penicillin as shown in Tables 2, 3, 4 and 5. These antibiotics were added to the basal rations in premixes. Feed and water were supplied ad libitum. Weight gain and feed efficiency data were evaluated statistically by analysis of variance.
871
OLEANDOMYCIN IN BROILER RATIONS TABLE 2.—Comparison of oleandomycin and penicillin in chick growth and feed conversion, experiments 1, 2 and 3 {batteries) Antibiotic
g./ton
Average Lb. feed/ weight 4 Lb. gain weeks, g. 4 weeks
494 502
5 5 25
522*
504 468 470
4 0.5 1.0 2.0 4.0
496*
482 475 473 481
4.0+1.0
455 474
4 1 4
479* 487*
1.46 1.44 1.44 1.44 1.62 1.72 1.68 1.62 1.68 1.65 1.66 1.71 1.66 1.67 1.69
' Significantly different (P<.05) from unsupplemented basal
TABLE 3.—Comparison of oleandomycin and penicillin in chick growth and feed conversion, Experiment 4 (floor pens) Average weight Antibiotic
Lb. feed/Lb. gain
g./ton
None Procaine penicillin Procaine penicillin Oleandomycin Oleandomycin Oleandomycin Oleandomycin Penicillin+oleandomycin Penicillin+oleandomycin
2 4 1 2 4 8 2+1 2+2
5 wks.
9 wks.
5 wks.
9 wks.
g600 615 606 617 647* 622 644* 625 620
g1,396 1,411 1,406 1,437 1,491* 1,437 1,455* 1,437 1,430
1.81 1.77 1.77 1.72 1.71 1.61 1.77 1.71 1.69
2.30 2.28 2.30 2.25 2.22 2.34 2.24 2.23 2.22
Significantly different (P<.05) from unsupplemented basal.
TABLE 4.—Time study of oleandomycin, experiment 5 {floor pens) Antibiotic , g./ton
Average weight
Lb. feed/Lb. gain
0-5 weeks
6-10 weeks
5 wks.
10 wks.
5 wks.
10 wks.
None Procaine penicillin, 10 None None None Oleandomycin, 0.5 Oleandomycin, 0.5 Oleandomycin, 1.0 Oleandomycin, 1.0 Oleandomycin, 10. Oleandomycin, 10.
None Procaine penicillin, 10 Oleandomycin, 0.5 Oleandomycin, 1.0 Oleandomycin, 10. None Oleandomycin, 0.5 None Oleandomycin, 1.0 None Oleandomycin, 10.
g569 578 573 564 567 602 585 589 587 598* 619*
g1,599 1,622 1,594 1,604 1,645 1,616 1,658 1,640 1,681 1,648 1,687
1.82 1.99 1.79 1.90 1.97 1.66 1.98 1.72 1.88 1.83 1.82
2.19 2.13 2.18 2.14 2.10 2.23 2.16 2.17 2.13 2.18 2.16
* Combined average weight was significantly different from combined average weight of the controls (P<.05).
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
Experiment 1 None Procaine penicillin Oleandomycin Oleandomycin Experiment Z None Procaine penicillin Oleandomycin Oleandomycin Oleandomycin Oleandomycin Penicillin -t-OIeandomycin Experiment 3 None Procaine penicillin Oleandomycin Oleandomycin
feed efficiency data for these three battery trials are shown in Table 2. Penicillin at 4 or 5 g. per ton produced only small growth responses which were not statistically significant (P<.05). Oleandomycin produced significant growth responses in each of the trials (P < .05), and in the two trials where low levels of this antibiotic were fed, growth with only one g. per ton was as good as with higher levels. Feed efficiency responses were small with both antibiotics and were not statistically significant. Oleandomycin fed with penicillin produced no better response than oleandomycin alone in experiment 2 which would
872
W. C. SHERMAN, G. A. DONOVAN, ^ . M. REYNOLDS AND H. G. LUTHER
obtained is of interest from a research standpoint and may be of practical value in poultry nutrition. It is suggested that the basis of the superior responses with oleandomycin may reside in certain differences between the antibacterial activity of this antibiotic and of penicillin. Published data on the antibacterial spectrum of oleandomycin (Sobin et al., 1955) shows that this antibiotic is primarily active against gram-positive organisms with distinct activity against several gram-negative bacteria. There are differences in the minimum inhibitory concentration of oleandomycin and penicillin required to affect various groups of organisms susceptible to the two antibiotics and it has been shown by Noyes et al. (1956) that oleandomycin is active against many strains of gram-positive Micrococcus pyogenes var. aureus which are resistant to penicillin.
Investigations of the microbial population of the intestine of chickens used in Experiment 5. The 5- and 10-week these studies and sensitivity tests of isoweight and feed efficiency data are given lates of micrococci from birds fed oleandoin Table 4. Penicillin fed continuously at mycin or penicillin were conducted to a level of 10 g. per ton enhanced growth determine whether growth effects were and feed efficiency only slightly. All three correlated with alterations of type or of levels of oleandomycin (0.5, 1.0 and 10 g. sensitivity of microflora (Price and Zolli, per ton) at 5 weeks produced heavier birds 1959), but negative results were obtained. with better feed efficiency than the 10 g. Studies with oleandomycin in chicks in per ton level of penicillin, and in the case a "new" environment or in an "old" enof the 10 g. per ton level of oleandomycin, vironment where antibiotics have not the difference between the combined aver- been fed would be of considerable interest age weight and the combined average of and could possibly yield valuable informathe control rations was statistically sig- tion on the mechanism of the action of nunificant (P < .05). Oleandomycin fed only tritional levels of antibiotics. during the starting or finishing periods SUMMARY produced heavier birds at 10 weeks but the growth responses were in no case as The antibiotic oleandomycin produced great as the corresponding level fed con- significant growth responses in chicks untinuously. der "old" environmental conditions in 3 battery trials and 2 floor pen trials and DISCUSSION was decidedly superior to penicillin in this The ability of low levels of oleando- respect. The simultaneous feeding of mycin to elicit sizable growth responses penicillin and oleandomycin under these in chicks under conditions where signifi- conditions did not improve the results obcant responses to penicillin are no longer tained with oleandomycin alone.
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
indicate that the entire growth promoting effect was due to the oleandomycin. Experiment 4. The 5- and 9-week weight and feed efficiency data of this floor pen experiment are presented in Table 3. Penicillin at 2 or 4 g. per ton produced only slight improvements in growth and feed efficiency which were not significant. Growth with all levels of oleandomycin (1, 2, 4 and 8 g. per ton) was superior to growth with penicillin and the differences from the negative control were statistically significant (P < .05) for the 2 and 8 g. per ton levels of oleandomycin at both ages. Six of the 8 feed efficiency values determined in this experiment were superior to the 4 penicillin values, although the differences were not statistically significant. Growth and feed efficiency of the two groups which were fed oleandomycin and penicillin simultaneously were not appreciably different from the corresponding values for groups fed oleandomycin alone.
OLEANDOMYCIN IN BROILER RATIONS
Carver, 1951. The effect of different antibiotics on growth of turkey poults. Poultry Sci. 30: 492-496. 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. Noyes, H. E., S. C. Nagle, Jr., J. P . Sanford and M. L. Robbins, 1956. Novobiocin and P.A. 105: In vitro and in vivo studies on effectiveness against micrococcus pyogenes. Antib. Chem. 6: 450-455. Price, K. E., and Z. Zolli, Jr., 1959. Influence of oleandomycin and penicillin on intestinal tract microflora of chickens. Poultry Sci. 38: 873-877. Sherman, W. C , G. A. Donovan, W. M. Reynolds and H. G. Luther, 1957. Nutritional evaluation of oleandomycin in poultry rations. Antibiotics Annual 1957-1958, New York, Med. Encyclopedia, Inc. p. 256-258. Sobin, B. A., A. R. English and W. D. Celmar, 1954. P.A. 105, a new antibiotic. Antibiotics Annual 1954-1955, New York, Med. Encyclopedia, Inc. p. 827-830. Stokstad, E. L. R., and T. H. Jukes, 1950. Growthpromoting effect of aureomycin on turkey poults. Poultry Sci. 29: 611-612. Supplee, W. C , G. F . Combs and D . L. Blamberg, 1958. Zinc and potassium effects on bone formation, feathering and growth of poults. Poultry Sci. 37: 63-67. Waibel, P. E., O. J. Abbott, C. A. Bowman and H. R. Berg, 1954. Disappearance of the growth response of chicks to dietary antibiotics in an "old" environment. Poultry Sci. 33: 1141-1146. Williams, O. M., and J. E. Hill, 1952. The effect of antibiotics on the growth of two varieties of turkey poults. Poultry Sci. 3 1 : 769-772.
Influence of Oleandomycin and Penicillin on Intestinal Tract Microflora of Chickens K. E. PRICE AND Z. ZOLLI, J R . Chas. Pfizer &• Co., Inc., Terre Haute, Ind. (Received for publication January 13, 1959)
I
N RECENT comparative experiments, oleandomycin has outperformed penicillin as a growth promotant for poultry. (McGinnis et al., 1958; Sherman et al., 1959). Despite apparent similarity in antimicrobial spectra of the two antibiotics, it is possible that quantitative differences in growth-promoting ability might be at-
tributed to different actions on the microflora of the gastro-intestinal tract. The present paper reports investigations of the influence of oleandomycin, penicillin, and an oleandomycin-penicillin combination on several microorganism populations in the gut of chickens. In addition, the influence of antibiotic
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
REFERENCES Almquist, H. J., and J. B. Merritt, 1951. Effects of vitamin Bu and crystalline aureomycin on growth of poalts. Poultry Sci. 30: 312. Branion, H. D., and D. C. Hill, 1951. The comparative effect of antibiotics on the growth of poults. Poultry Sci. 30: 793-798. Coates, M. E., D. C. Dickinson, G. F. Harrison, S. K. Kon, S. R. Cummins and W. F. J. Cuthbertson, 1951. Mode of action of antibiotics in stimulating growth of chicks. Nature, 168: 332. Gordon, H. A., 1952. A morphological and biochemical approach in a colloquium: Studies on the growth effect of antibiotics in germ-free animals. Colloquium, Lobund Inst., Univ. of Notre Dame, June 4. Heuser, G. F., and L. C. Norris, 1952. Some results of feeding antibiotics to chicks. Poultry Sci. 3 1 : 857-862. Hill, D. C , H. D. Branion, S. J. Slinger and G. W. Anderson, 1953. Influence of environment on the growth response of chicks to penicillin. Poultry Sci. 32: 462-466. Libby, D. A., and P. J. Schaible, 1955. Observations on growth responses to antibiotics and arsonic acids in poultry feeds. Science, 121: 733-735. Lillie, R. J., and H. R. Bird, 1952. Effect of antibiotic supplements upon hatchability and upon growth and viability and progeny. Poultry Sci. 31:513-518. Lillie, R. J., J. R. Sizemore and H. R. Bird, 1953. Environment and stimulation of growth of chicks by antibiotics. Poultry Sci. 32: 466-475. Matterson, L. D., and E . P. Singsen, 1951. A comparison of several antibiotics as growth stimulants in practical chick starting rations. Storrs (Connecticut) Agric. Expt. Sta. Bui. 275. McGinnis, J., R. R. Stern, R. A. Wilcox and J. S.
873
sponses to antibiotics in their laboratory had decreased from 19 percent in 1950 to 3.3 percent in 1953 during which period the growth of the negative controls had steadily improved so that in 1953 the growth without antibiotics was 19 percent better than in 1950. They likewise suggested that the environmental germ load or disease potential had been lowered by the continuous use of antibiotics. This interpretation is further supported by the failure to obtain significant antibiotic responses in chicks under germ-free conditions by Gordon (1952) or in a "new" environment not previously used in chick rearing (Coates et al., 1951; Hill et al., 1953; and Lillie et al., 1953). Under our laboratory conditions where antibiotics have been fed in most experiments, chick responses to penicillin are variable and in recent years have been relatively small. Early chick trials with a new antibiotic oleandomycin* (Sherman et al., 1957) indicated that sizable growth responses could be obtained with nutritional levels of this antibiotic under conditions where penicillin responses were relatively small. Outstanding oleandomycin responses in turkey poults fed synthetic rations were reported by Supplee et al. (1958) and with practical rations, oleandomycin produced several times the growth increment obtained with penicillin (McGinnis et al., 1958). It is the purpose of this paper to present data from addi* Trademark of Chas. Pfizer & Co., Inc. for oleandomycin is Matromycin.
869
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
I
N EARLY nutrition studies with antibiotics in chicks (Matterson and Singsen, 1951; Heuser and Norris, 1952; and Lillie and Bird, 1952), consistent and relatively large growth responses were obtained in the range of 10 to 20 percent. Similarly with turkey poults, reports of early experiments by Stokstad and Jukes (1950), Almquist and Merritt (1951), Branion and Hill (1951), McGinnis et al. (1951) and Williams and Hill (1952) showed growth responses to antibiotics of 20 percent to over 40 percent. Under conditions of continuous feeding of antibiotics with relatively good sanitation some investigators have observed that in recent years the percentage response to antibiotics has decreased. This diminished antibiotic response has been associated with a pronounced improvement with time in the performance of the non-supplemented control groups rather than a decreased growth rate of the antibiotic-supplemented groups. Waibel et al. (1954) reported results of antibiotic trials conducted in an "old" environment during the years 1950, '51, '52 and '53 during which period the antibiotic response steadily decreased and it was observed that the antibiotic response was large when the growth of the control groups was poor, and small with goodgrowing control groups. The authors concluded that possibly the harmful bacteria of the environment had been eliminated through the continuous use of antibiotics. Libby and Schaible (1955) reported that during these same years chick growth re-
870
W. C. SHERMAN, G. A. DONOVAN, W. M. REYNOLDS AND H. G. LUTHER
tional chick trials to evaluate oleandomycin at lower levels, and to investigate combinations of this antibiotic with penicillin under battery conditions and under practical conditions of floor-pen operation. EXPERIMENTAL
RESULTS
Experiments 1, 2 and 3. Growth and
TABLE 1.—Composition of basal diets 5
4 Experiment N o .
1
2 &3 0-5 wks.
Ground yellow corn Soybean oil meal ( 5 1 % protein) Soybean oil meal (44% protein) Corn gluten meal Corn oil Stabilized animal fat Fish meal (Menhaden, 6 0 % protein) Dried distillers solubles Dried whey-product (50% lactose) Dried brewers yeast Dehydrated alfalfa (17% protein) CaCOj Dicalcium phosphate Na 2 HP04 Salt, iodized Mineral mix a BHTb DL-Methionine Vigofac c Nicarbazin (coccidiostat) Vitamin mix l d Vitamin mix 2 Vitamin mix 3 Protein Prod, energy Cal./lb. Cal. /protein
50.78 38.15
56.45
— — 6.10 — — — — — — 1.40
26.94 2.50
1.35 0.46 0.61 0.10 0.0125 0.14 0.30
—
— 1.50 4.00 1.00 1.00 1.50 2.00 1.30 1.00
— 0.40 0.10
— 0.60 — —
— — — — 0.30 —
24.00 1,008.00 42.00
22.16 929.00 42.00
0.01
6-9 wks.
0-5 wks.
6-10 wks. 62.83 18.42
51.07 38.15
66.15 27.68
49.15 28.65
— — 6.10 — — — — — — 1.40
— — 1.49 — — — — — — 1.40
— 2.50 — 5.98
—
4.00 1.00 1.00 1.50 2.00 1.23 1.67
4.00 1.00 1.00 1.50 2.00 1.23 1.67
— 0.50
— 0.50
0.10 0.0125 0.10
0.10 0.0125 0.10
— 0.0125 — — 0.60
— 0.0125 — — 0.60
1.35 0.46 0.61 0.10 0.0125 0.14
— 0.0125
1.35 0.46 0.61 0.10 0.0125 0.14
—
0.60
0.0125 0.60
— —
— —
24.00 1,008.00 42.00
20.00 980.00 49.00
24.00 1,008.00 42.00
•
2.50
— 2.53
20.00 1,000.00 50.00
* Mineral mix contained the following percentages: Ca 27.0, M n 6.0, F e 2 . 0 , 1 0.12, Cu 0.20, Co 0.02 a n d Zn 0.006%. Butylated hydroxytoluene, antioxidant. ° Trademark of Chas. Pfizer & Co., Inc. for fermentation source of unidentified growth factors. d Vitamin mix 1 supplied the following per lb. of ration: vitamin A, 4,500 U.S.P. units; vitamin D3, 680 I.C. units; vitamin B12; 12.5 meg.; niacin, 12 mg.; choline chloride, 230 mg.; riboflavin, 2.5 mg.; pantothenic acid, 5 mg.; pyridoxine, 3 rag.; vitamin E ; 100 I.U.; and menadione bisulfite, 1.4 mg. Vitamin mix 2 supplied the following per lb. of ration: vitamin A, 2,250 U.S.P. u n i t s ; vitamin D3, 340 I.C. units; vitamin B12, 20 meg.; niacin, 5 mg.; cholune chloride, 180 mg.; riboflavin, 2.4 mg.; and pantothenic acid, 2.5 mg. Vitamin mix 3 supplied the following per lb. of ration: vitamin A, 2,250 U.S.P. units; vitamin D3, 680 I.C. units; vitamin Bis, 12.5 meg.; niacin, 12 mg.; choline chloride, 230 mg.; riboflavin, 2.4 mg.; pantothenic acid, 4 mg.; and vitamin E, 100 I.U.
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
Three starting chick and two practical broiler experiments were conducted. Nichol's Lancaster White Cross chicks were used in all experiments except experiment 5 in which the birds were Thompson White Rock strain. In experiments 1, 2 and 3 the day-old chicks were raised to 4 weeks of age in wire-floored electrically heated batteries. Quadruplicate groups of 10 chicks (5 males and 5 females) were fed the basal diets given in Table 1, supplemented as shown in succeeding tables. In experiments 4 and 5, birds were raised to 9 and 10 weeks respectively in 8'X12' floor pens with 25 males and 25 females
randomly placed in each pen. The negative controls were run in quadruplicate and each treatment in duplicate. Pens were assigned to each treatment under a system of restricted randomization to permit evaluations of pen location effect. The starting basal diets, shown in Table 1, were fed to 4 weeks in the battery trials and to 5 weeks in the floor pen trials; the finishers were fed for the remainder of the floor pen experiments. The treatment groups were supplemented with crystalline oleandomycin or procaine penicillin as shown in Tables 2, 3, 4 and 5. These antibiotics were added to the basal rations in premixes. Feed and water were supplied ad libitum. Weight gain and feed efficiency data were evaluated statistically by analysis of variance.
871
OLEANDOMYCIN IN BROILER RATIONS TABLE 2.—Comparison of oleandomycin and penicillin in chick growth and feed conversion, experiments 1, 2 and 3 {batteries) Antibiotic
g./ton
Average Lb. feed/ weight 4 Lb. gain weeks, g. 4 weeks
494 502
5 5 25
522*
504 468 470
4 0.5 1.0 2.0 4.0
496*
482 475 473 481
4.0+1.0
455 474
4 1 4
479* 487*
1.46 1.44 1.44 1.44 1.62 1.72 1.68 1.62 1.68 1.65 1.66 1.71 1.66 1.67 1.69
' Significantly different (P<.05) from unsupplemented basal
TABLE 3.—Comparison of oleandomycin and penicillin in chick growth and feed conversion, Experiment 4 (floor pens) Average weight Antibiotic
Lb. feed/Lb. gain
g./ton
None Procaine penicillin Procaine penicillin Oleandomycin Oleandomycin Oleandomycin Oleandomycin Penicillin+oleandomycin Penicillin+oleandomycin
2 4 1 2 4 8 2+1 2+2
5 wks.
9 wks.
5 wks.
9 wks.
g600 615 606 617 647* 622 644* 625 620
g1,396 1,411 1,406 1,437 1,491* 1,437 1,455* 1,437 1,430
1.81 1.77 1.77 1.72 1.71 1.61 1.77 1.71 1.69
2.30 2.28 2.30 2.25 2.22 2.34 2.24 2.23 2.22
Significantly different (P<.05) from unsupplemented basal.
TABLE 4.—Time study of oleandomycin, experiment 5 {floor pens) Antibiotic , g./ton
Average weight
Lb. feed/Lb. gain
0-5 weeks
6-10 weeks
5 wks.
10 wks.
5 wks.
10 wks.
None Procaine penicillin, 10 None None None Oleandomycin, 0.5 Oleandomycin, 0.5 Oleandomycin, 1.0 Oleandomycin, 1.0 Oleandomycin, 10. Oleandomycin, 10.
None Procaine penicillin, 10 Oleandomycin, 0.5 Oleandomycin, 1.0 Oleandomycin, 10. None Oleandomycin, 0.5 None Oleandomycin, 1.0 None Oleandomycin, 10.
g569 578 573 564 567 602 585 589 587 598* 619*
g1,599 1,622 1,594 1,604 1,645 1,616 1,658 1,640 1,681 1,648 1,687
1.82 1.99 1.79 1.90 1.97 1.66 1.98 1.72 1.88 1.83 1.82
2.19 2.13 2.18 2.14 2.10 2.23 2.16 2.17 2.13 2.18 2.16
* Combined average weight was significantly different from combined average weight of the controls (P<.05).
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
Experiment 1 None Procaine penicillin Oleandomycin Oleandomycin Experiment Z None Procaine penicillin Oleandomycin Oleandomycin Oleandomycin Oleandomycin Penicillin -t-OIeandomycin Experiment 3 None Procaine penicillin Oleandomycin Oleandomycin
feed efficiency data for these three battery trials are shown in Table 2. Penicillin at 4 or 5 g. per ton produced only small growth responses which were not statistically significant (P<.05). Oleandomycin produced significant growth responses in each of the trials (P < .05), and in the two trials where low levels of this antibiotic were fed, growth with only one g. per ton was as good as with higher levels. Feed efficiency responses were small with both antibiotics and were not statistically significant. Oleandomycin fed with penicillin produced no better response than oleandomycin alone in experiment 2 which would
872
W. C. SHERMAN, G. A. DONOVAN, ^ . M. REYNOLDS AND H. G. LUTHER
obtained is of interest from a research standpoint and may be of practical value in poultry nutrition. It is suggested that the basis of the superior responses with oleandomycin may reside in certain differences between the antibacterial activity of this antibiotic and of penicillin. Published data on the antibacterial spectrum of oleandomycin (Sobin et al., 1955) shows that this antibiotic is primarily active against gram-positive organisms with distinct activity against several gram-negative bacteria. There are differences in the minimum inhibitory concentration of oleandomycin and penicillin required to affect various groups of organisms susceptible to the two antibiotics and it has been shown by Noyes et al. (1956) that oleandomycin is active against many strains of gram-positive Micrococcus pyogenes var. aureus which are resistant to penicillin.
Investigations of the microbial population of the intestine of chickens used in Experiment 5. The 5- and 10-week these studies and sensitivity tests of isoweight and feed efficiency data are given lates of micrococci from birds fed oleandoin Table 4. Penicillin fed continuously at mycin or penicillin were conducted to a level of 10 g. per ton enhanced growth determine whether growth effects were and feed efficiency only slightly. All three correlated with alterations of type or of levels of oleandomycin (0.5, 1.0 and 10 g. sensitivity of microflora (Price and Zolli, per ton) at 5 weeks produced heavier birds 1959), but negative results were obtained. with better feed efficiency than the 10 g. Studies with oleandomycin in chicks in per ton level of penicillin, and in the case a "new" environment or in an "old" enof the 10 g. per ton level of oleandomycin, vironment where antibiotics have not the difference between the combined aver- been fed would be of considerable interest age weight and the combined average of and could possibly yield valuable informathe control rations was statistically sig- tion on the mechanism of the action of nunificant (P < .05). Oleandomycin fed only tritional levels of antibiotics. during the starting or finishing periods SUMMARY produced heavier birds at 10 weeks but the growth responses were in no case as The antibiotic oleandomycin produced great as the corresponding level fed con- significant growth responses in chicks untinuously. der "old" environmental conditions in 3 battery trials and 2 floor pen trials and DISCUSSION was decidedly superior to penicillin in this The ability of low levels of oleando- respect. The simultaneous feeding of mycin to elicit sizable growth responses penicillin and oleandomycin under these in chicks under conditions where signifi- conditions did not improve the results obcant responses to penicillin are no longer tained with oleandomycin alone.
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
indicate that the entire growth promoting effect was due to the oleandomycin. Experiment 4. The 5- and 9-week weight and feed efficiency data of this floor pen experiment are presented in Table 3. Penicillin at 2 or 4 g. per ton produced only slight improvements in growth and feed efficiency which were not significant. Growth with all levels of oleandomycin (1, 2, 4 and 8 g. per ton) was superior to growth with penicillin and the differences from the negative control were statistically significant (P < .05) for the 2 and 8 g. per ton levels of oleandomycin at both ages. Six of the 8 feed efficiency values determined in this experiment were superior to the 4 penicillin values, although the differences were not statistically significant. Growth and feed efficiency of the two groups which were fed oleandomycin and penicillin simultaneously were not appreciably different from the corresponding values for groups fed oleandomycin alone.
OLEANDOMYCIN IN BROILER RATIONS
Carver, 1951. The effect of different antibiotics on growth of turkey poults. Poultry Sci. 30: 492-496. 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. Noyes, H. E., S. C. Nagle, Jr., J. P . Sanford and M. L. Robbins, 1956. Novobiocin and P.A. 105: In vitro and in vivo studies on effectiveness against micrococcus pyogenes. Antib. Chem. 6: 450-455. Price, K. E., and Z. Zolli, Jr., 1959. Influence of oleandomycin and penicillin on intestinal tract microflora of chickens. Poultry Sci. 38: 873-877. Sherman, W. C , G. A. Donovan, W. M. Reynolds and H. G. Luther, 1957. Nutritional evaluation of oleandomycin in poultry rations. Antibiotics Annual 1957-1958, New York, Med. Encyclopedia, Inc. p. 256-258. Sobin, B. A., A. R. English and W. D. Celmar, 1954. P.A. 105, a new antibiotic. Antibiotics Annual 1954-1955, New York, Med. Encyclopedia, Inc. p. 827-830. Stokstad, E. L. R., and T. H. Jukes, 1950. Growthpromoting effect of aureomycin on turkey poults. Poultry Sci. 29: 611-612. Supplee, W. C , G. F . Combs and D . L. Blamberg, 1958. Zinc and potassium effects on bone formation, feathering and growth of poults. Poultry Sci. 37: 63-67. Waibel, P. E., O. J. Abbott, C. A. Bowman and H. R. Berg, 1954. Disappearance of the growth response of chicks to dietary antibiotics in an "old" environment. Poultry Sci. 33: 1141-1146. Williams, O. M., and J. E. Hill, 1952. The effect of antibiotics on the growth of two varieties of turkey poults. Poultry Sci. 3 1 : 769-772.
Influence of Oleandomycin and Penicillin on Intestinal Tract Microflora of Chickens K. E. PRICE AND Z. ZOLLI, J R . Chas. Pfizer &• Co., Inc., Terre Haute, Ind. (Received for publication January 13, 1959)
I
N RECENT comparative experiments, oleandomycin has outperformed penicillin as a growth promotant for poultry. (McGinnis et al., 1958; Sherman et al., 1959). Despite apparent similarity in antimicrobial spectra of the two antibiotics, it is possible that quantitative differences in growth-promoting ability might be at-
tributed to different actions on the microflora of the gastro-intestinal tract. The present paper reports investigations of the influence of oleandomycin, penicillin, and an oleandomycin-penicillin combination on several microorganism populations in the gut of chickens. In addition, the influence of antibiotic
Downloaded from http://ps.oxfordjournals.org/ at Swinburne University of Technology on May 16, 2015
REFERENCES Almquist, H. J., and J. B. Merritt, 1951. Effects of vitamin Bu and crystalline aureomycin on growth of poalts. Poultry Sci. 30: 312. Branion, H. D., and D. C. Hill, 1951. The comparative effect of antibiotics on the growth of poults. Poultry Sci. 30: 793-798. Coates, M. E., D. C. Dickinson, G. F. Harrison, S. K. Kon, S. R. Cummins and W. F. J. Cuthbertson, 1951. Mode of action of antibiotics in stimulating growth of chicks. Nature, 168: 332. Gordon, H. A., 1952. A morphological and biochemical approach in a colloquium: Studies on the growth effect of antibiotics in germ-free animals. Colloquium, Lobund Inst., Univ. of Notre Dame, June 4. Heuser, G. F., and L. C. Norris, 1952. Some results of feeding antibiotics to chicks. Poultry Sci. 3 1 : 857-862. Hill, D. C , H. D. Branion, S. J. Slinger and G. W. Anderson, 1953. Influence of environment on the growth response of chicks to penicillin. Poultry Sci. 32: 462-466. Libby, D. A., and P. J. Schaible, 1955. Observations on growth responses to antibiotics and arsonic acids in poultry feeds. Science, 121: 733-735. Lillie, R. J., and H. R. Bird, 1952. Effect of antibiotic supplements upon hatchability and upon growth and viability and progeny. Poultry Sci. 31:513-518. Lillie, R. J., J. R. Sizemore and H. R. Bird, 1953. Environment and stimulation of growth of chicks by antibiotics. Poultry Sci. 32: 466-475. Matterson, L. D., and E . P. Singsen, 1951. A comparison of several antibiotics as growth stimulants in practical chick starting rations. Storrs (Connecticut) Agric. Expt. Sta. Bui. 275. McGinnis, J., R. R. Stern, R. A. Wilcox and J. S.
873