746
S. J. SLINGER AND W. F. PEPPER in the diet of the chick. J. Biol. Chem. 138: 467469. Riedel, B. B., 1954. Tryptophane and its relationship to ascarid infections in New Hampshire chicks. Poultry Sci. 38: 80-84. Riedel, B. B., 1950. The role of lysine upon the resistance of chickens to Ascaridia. Poultry Sci. 29: 903-906. Todd, A. C , 1951. Supplemental methionine in the diet of parasitized chicks. Poultry Sci. 30: 820824.
Effect of Penicillin on the Growth and Feed Consumption of Turkey Poults 1 S. J. SLINGER AND W. F. PEPPER Department of Poultry Husbandry, Ontario Agricultural College, Guelph, Ontario (Received for publication October 26, 1953)
and Glista (1950) found that SCOTT the inclusion of aureomycin in a chick diet gave a slight but insignificant growth response with ad libitum feeding and no growth response when feed intake was equated. Brown el al. (1953), working with pigs, observed a marked growth response to aureomycin on an unlimited feeding regime but no significant difference when the pigs were given an equalized feed intake. Previous work in this laboratory (Slinger et al., 1953a) showed that penicillin caused a significant increase in weight with chicks having free access to feed but no increase when feed intake was restricted. In this work it was also observed that, with chicks fed ad libitum, penicillin resulted in greater daily feed consumption per chick almost without exception for the first 28 days after hatching. On the other hand, feed consumption per unit of body weight was increased by the antibiotic 1
This work was supported, in part, by a grant from Merck and Company Inc., Rahway, N. T.
only to about 16 days of age. These results suggest that penicillin stimulates growth in the chick mainly by causing an increase in feed intake early in the life of the bird. The present experiments were made to determine the influence of penicillin on the growth of poults fed both free choice and on an equalized feed intake regime. GENERAL PROCEDURE
Day old Broad Breasted Bronze poults were vent-sexed and weighed individually. They were then assigned to the experimental groups on the basis of sex and weight. The birds were reared in electrically heated battery brooders for the duration of the trials. The percentage composition of the basal diet was as follows: ground wheat 23, ground yellow corn 15, ground oat groats 5, dehydrated alfalfa meal 3, fish meal (65% protein) 2, meat meal (50% protein) 2, dried buttermilk 2, soybean oil meal (44% protein) 43, soybean oil 1, ground limestone 2, steamed bone meal
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acid requirement of the chick. J. Nutrition, 28: 325-331. Briggs, G. M., Jr., R. C. Mills, C. A. Elvehjem and E. B. Hart, 1942. The effect of added cystine in purified rations for the chick. J. Biol. Chem. 144: 47-52. Brown, S. O., M. C. Wilkening and B. S. Schweigert, 1948. Some histological manifestations of a tryptophane deficiency in the chick. Proc. Soc. Exp. Biol. Med. 68: 672-675. Klose, A. A., and H. J. Almquist, 1941. Methionine
747
PENICILLIN AND POULT GROWTH
TABLE 1.—Effect
there was little mortality, probably introduced no appreciable error. EXPERIMENT 1
This experiment comprised four groups of 20 male and 20 female poults. The birds were weighed individually at 14 and 28 days of age and feed consumption was computed to these ages. The rate of growth was calculated for the periods from 1 to 14 days and from 14 to 28 days using the logarithmic method (see Brody, 1927). The results are presented in Table 1. Penicillin caused a slight increase in weight at 14 days of age with equalized feed intake and a considerably greater increase when feed was offered free choice. The weight data at 28 days of age were examined statistically by the " t " test (Snedecor, 1946). At this time penicillin resulted in a weight increase which was highly significant with poults having free access to feed but no significant increase with the restricted feeding regime. Similarly, feed efficiency was improved by penicillin during both the 1 to 14 and 14 to 28 day periods with ad libitum feeding but only during the initial period when feed intake was equated. It may be noted that penicillin caused a marked increase in the rate of growth during the 1 to 14 day period with ad
of penicillin and method oj feeding on growth and feed efficiency of poults Results at 28 days of age
Results at 14 days of age Feeding method
Diet
Rate of Feed/gain Av. wt.f growth* (1-14 (gm.) 1-14 days days)
Av. wt. (gm.)
Rate of growth 14-28 days (%)
471 533 446 452
6.77 6.74 6.63 6.40
(%)
Basal Basal+Pen. Basal Basal+Pen. * R =
Free choice Free choice Equalized Equalized
LogT
183 208 176 185
9.01 9.98 8.80 9.14
1.50 1.39 1.44 1.35
Feed/gain (14-28d) (l-28d) 1.88 1.79 1.88 1.90
1.76 1.66 1.74 1.71
^ 2 — l o g W i x 2.303X100, where Wi and Wt are the first and final weights at times h and h.
t Unweighted mean of 20 cf and 20 9 poults per treatment.
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1.5, iodized salt 0.5. In addition, to each 100 pounds of diet the following (in grams) were added: vitamin A oil (10,000 I.U./gm.) 45.4, dry vitamin D 3 (1,500 I.C.U./gm.) 45.4, manganese sulfate 6, DL methionine 11.3, riboflavin 0.15, niacin 0.75 and vitamin Bi2 supplement (3 mg. Bi 2 /pound) 45.4. Various groups were fed this basal diet or the same diet plus 15 p.p.m. of procaine penicillin G both on the basis of free choice and equalized feed intake. In both experiments feeding was carried out daily with similar groups of birds on the equalized feed intake regime receiving the same amount of feed daily as was consumed by the group on the free choice regime which consumed the least on the previous day. The groups fed the basal diet controlled feed consumption almost every day in both experiments. Tap water was freely accessible at all times. Extra groups of birds were carried as spares to replace birds which died in the experimental groups. These were from the same hatch as the birds on experiment and were maintained on the test diets. If a bird died during the course of the trial it was replaced by a bird of the same sex and weight and which had been receiving the same diet. This simplified determination of the amount of feed to give and, since
748
S. J. SLINGER AND W. F. PEPPER
day period. EXPERIMENT 2
From the results of experiment 1 it would appear that the growth promoting effect of penicillin for the turkey poult is brought about chiefly through an increase in feed consumption. Furthermore, the data indicate that growth is not stimulated after a short initial period even with ad libitum feeding. Assuming that the mode of action of the antibiotic, in stimu-
3 4 5 6 7 8
lating growth, is solely by way of an increase in feed intake then the effect on feed consumption should parallel the influence on growth rate. The present experiment was made in an attempt to test this hypothesis and to determine the age beyond which the antibiotic no longer exerts a growth stimulating effect. The experiment was conducted both with male and female poults and comprised either 15 female or 13 male poults per group. Records of feed consumption and body weight were maintained daily for a 25 day period. The birds were weighed in groups on all but the final day when they were weighed individually. Since the effect of penicillin and the method of feeding was similar in the case of both sexes, excepting for a somewhat greater response to the antibiotic by males than by females, the values for weight and feed consumption are presented in terms of unweighted means of the two sexes. The influence of penicillin on feed consumption per poult and per unit body weight for birds fed ad libitum is shown in
9 to // 12 13 14 15 16 17 18 19 20 21 22 23 24 25 TIME IN DAYS
FIG. 1. Influence of penicillin on feed consumption per poult and per unit body weight.
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libitum feeding and a much smaller increase when feed intake was controlled. It is of interest that, during the 14 to 28 day period, the antibiotic caused no growth stimulation with either method of feeding and actually depressed the rate of growth in the pair fed birds. This was true in spite of the fact that, with birds fed free choice, those receiving penicillin gained 325 grams as compared with a gain of 288 grams for the control group, and that in the pair-fed birds, there was practically no difference in weight gain between the two groups during the 14 to 28
749
PENICILLIN AND POULT GROWTH i
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2 3 4 5 6 7 8 9 to 11 12 13 14 15 16 I? I& 19 20 21 22 23 24 25 TIME IN DAYS FIG. 2. Effect of penicillin on growth of poults fed free choice.
Figure 1. The antibiotic resulted in greater feed consumption per poult each day for the entire period. On the other hand, considered on a unit weight basis, the antibiotic enhanced feed intake to 6 days of age, effected little change from 6 to 17 days of age and caused a decrease in feed consumption during the 17 to 25 day period. The average daily weights for groups
fed free choice and on the paired feeding regime are plotted in Figures 2 and 3, respectively. Statistical analysis of the weights at 25 days of age indicated that penicillin caused a highly significant difference with birds fed free choice. When feed intake was restricted the penicillin effect was smaller and proved to be nonsignificant. In spite of the lack of statistical support, since penicillin also caused a
10 II 12 13 14 15 16 17 18 19 2o 21 22 23 24 25 TIME IN DAYS FIG. 3. Effect of penicillin on growth of poults with equalized feed intake.
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S. J. SLINGER AND W. F. PEPPER
shape of the curves relating feed consumption and unit body weight are probably explained, to a large extent, on the basis of basal energy metabolism per unit live weight. It is therefore interesting to speculate as to whether the differences in feed intake per unit body weight, resulting from penicillin, may not also have a basis in differences in metabolic activity. It may be that an increase in basal metabolic rate early in the life of the bird is part of the mechanism whereby the antibiotic aids in the development of defences against intestinal microorganisms. Such increase could help to explain the greater feed consumption per unit body weight and consequent growth promoting activity of the antibiotic. A point of interest is the difference in the way in which poults grew in the absence and presence of antibiotic when fed ad libitum. In the control group there was the customary slow growth during an initial induction period and the rate of growth increased with advancing age. In the presence of penicillin, on the other hand, there was no lag period at the start and the rate of growth decreased with increasing age. This latter curve probably represents the true potential of the poult to grow, with the induction period characterizing the growth curve in the absence of antibiotic being due to an abnormal intestinal flora. In an attempt to determine the age beyond which the antibiotic no longer caused growth stimulation, with free choice feeding, the daily rates of growth were plotted against time. While there was considerable variation from day to day, thus making it difficult to arrive at a definite age, the data suggest that penicillin caused a marked response only to the age of 8 days. From 8 to 21 days of age there was a slight positive response and from 21 to 25 days a relatively
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slight response in the previous trial with pair-fed birds, it appears likely that the difference may be a real one. The feed:gain ratios at 25 days of age were 1.80 and 1.64 for the groups having free access to feed and 1.75 and 1.68 for the pair-fed groups in the absence and presence of penicillin, respectively. Thus, while the improvement was not as great as with ad libitum feeding, penicillin caused some increase in feed efficiency with equalized feed intake. As in the previous experiment the improvement in feed efficiency in pair-fed birds was accountable to the initial period of life. Plotting the logarithms of the daily weights against time gave essentially straight lines in every case. It was therefore justifiable to determine the rate of growth for any period on the curves. The rate of growth was calculated for the periods from 1 to 6, 6 to 17 and 17 to 25 days since the effect of penicillin on feed consumption per unit body weight differed during each of these intervals. The method used was that previously indicated. These values are shown in Figures 2 and 3. With the birds fed free choice, penicillin effected a marked increase in the rate of growth for the 1 to 6 day period and a smaller increase during the 6 to 17 day period. The fact that there was an increase in the growth rate from 6 to 17 days of age in spite of the finding that the antibiotic did not increase feed consumption per unit body weight during this time is further evidence that the mechanism of response is not entirely by way of enhanced feed intake. It may be noted that the antibiotic-fed birds grew more slowly than the control group for the 17 to 25 day period. However, this was to be expected in view of the fact that the antibiotic depressed considerably feed intake per unit of body weight during this interval. The
751
PENICILLIN AND POULT GROWTH TABLE 2.—Effect
of penicillin on growth of turkeys from hatching through 24 weeks of age Gain in weight (gm.) and rate of growth (%)
Average weight in grams Age 4 weeks
(%) (
528 (153) 628 (154) 100
Age 24 weeks
1,687(144) 8,582(127) 1,932(151) 8,972(137) 245
18.93
14.52
4-8 wks. gms. %
4-24 wks. gms. %
8-24 wks. gms. %
1,159 4.15 1,304 4.01
8,054 1.99 8,344 1.90
6,895 1.45 7,040 1.37
390 4.54
) Number of birds surviving.
marked negative response. Comparing these results with the values for feed consumption it is apparent that, except for a small additional positive growth response, the effect of the antibiotic on growth rate parallels the effect on feed consumption per unit body weight. With the pair-fed groups (Figure 3) the antibiotic increased rate of growth only during the first 6 days after which there was a slight decrease attributable to the drug. It is thus apparent that the difference in weight at 25 days of age is accountable to the early period of life. In this case both the growth curves exhibited induction periods with growth rates increasing with age. Since the above experiments were of relatively short duration some question arises as to the possible growth promoting activity of penicillin over a longer period. To obtain information on this point the results of a previous experiment from this laboratory (Slinger et al., 1953b) were utilized. In that work various paired groups of poults were fed diets with and without penicillin from hatching through 24 weeks of age. The 8 and 24 week data for the several groups receiving the control diets or these diets plus penicillin have been combined for presentation in Table 2. The results at 4 weeks of age were not given in the previous report but
are presented in Table 2. It may be noted that penicillin resulted in greater numerical increases in weight at 8 and 24 weeks than at 4 weeks of age. Furthermore, the poults fed penicillin gained more during each interval than the control birds. In spite of this penicillin did not stimulate growth during these periods. In fact, the group fed penicillin grew somewhat less rapidly than the control group during the 4 to 8, 4 to 24 and 8 to 24 week periods. That is, the difference in weight in favor of the group receiving penicillin, at 24 weeks of age, is attributable to the fact that they gained more during the first 4 weeks of life. These results, together with those presented above, serve to emphasize the fallacy of using numerical weight gains based on different starting weights as a basis for determining growth promoting activity. It should be borne in mind that the increase in weight at any moment is proportional to the size already attained. While the present results suggest that penicillin does not stimulate growth after a short initial period this does not necessarily mean that the antibiotic could be removed from the diet, in practice, with assurance of obtaining maximum response at marketing time. Moving the birds to a new location or changes in environment for other reasons could conceivably in-
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No Penicillin Plus Penicillin Increase due pen. (gms.) Increase due pen.
Age 8 weeks
752
S. J. SLINGER AND W. F. PEPPER
Sieburth et al. (1952) reported that restricting the feed intake of poults receiving penicillin to that of poults fed the basal diet did not eliminate the growth promoting effect of the antibiotic. However, both groups received penicillin and an unlimited supply of feed for the first week, which, according to our results, is the most critical period. Furthermore, since they used unsexed poults and obtained a difference in weight not much greater than the difference between the sexes, their conclusions are open to some question. Coates et al. (1952), as a result of their work, postulated that chicks reared in previously used quarters show a growth depression caused by an "infection" sensitive to the antibiotic. On the basis of the present data it is clear that the growth depression can only be alleviated by penicillin when the birds are permitted to consume additional feed. Overcoming a true infection might be expected to result
in a much greater response in pair-fed birds than was the case. On the other hand, as indicated by the data for both pair-fed birds and those fed ad libitum, enhanced feed intake was not solely responsible for the antibiotic effect. Considering the possibility that a portion of the penicillin effect might be attributable to the suppression of an infection, the rectal temperatures of the males on the free choice regime were measured at 24 days of age. The average temperature of the birds on the basal diet was found to be 106.5+ .16° and that of the birds receiving penicillin 106.7 + .11°. This indicates that if an infection were present it did not result in an elevated body temperature. Many experiments have been made in an attempt to explain the mechanism of the growth promoting action of antibiotics on the basis of intestinal floral alterations. In work of this kind little attention appears to have been paid to the age of the birds involved. The results of the present experiments serve to emphasize the importance of the age factor and indicate that antibiotic-induced intestinal floral changes occurring during the first week of life are of greatest importance. SUMMARY
Experiments were made to determine the effect of penicillin on the growth of turkey poults to 25 and 28 days of age with both free choice and equalized feed intake. The results indicate that, under the conditions employed, the mode of action of penicillin in stimulating the growth of turkey poults may be explained largely, though not entirely, on the basis of the increased feed consumption per unit of body weight which occurs during the first week of life.
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troduce pathogenic or other microorganisms to which the birds have not become adapted. Without the protective action of an antibiotic such microorganisms might well result in growth depression. Davis and Briggs (1951) presented evidence showing that the growth response of poults obtained with antibiotics could not be explained in terms of increased feed consumption. In some cases, the amount of feed consumed by groups receiving an antibiotic was less than that of untreated birds, even though a growth response was obtained. In their work weight and feed consumption data were recorded only at 6 weeks of age. It may be, however, that feed consumption was enhanced by the antibiotic early in the life of the poults, that is, during the time growth was being stimulated by the antibiotic, even though this increase was not in evidence at 6 weeks of age.
MICROBIOLOGY or ANTIBIOTIC-FED CHICKS REFERENCES
aureomycin and arsonic acid on chick growth. Poultry Sci. 29: 921-923. Sieburth, J. M., J. R. Stern and J. McGinnis, 1952. The effect of antibiotics and fecal preparations on growth of turkey poults. Poultry Sci. 31:625-627. Slinger, S. J., M. M. Hauser and W. F. Pepper, 1953a. The correlation between feed consumption and fecal flora in chicks. Poultry Sci. 32:925. Slinger, S. J., W. F. Pepper, A. M. Morphet and E. V. Evans, 1953b. Effect of penicillin on the niacin requirement of turkeys and a carry-over effect of penicillin from dams to progeny. Poultry Sci. 32:754-762. Snedecor, G. W., 1946. Statistical Methods. Fourth Edition. The Iowa State College Press, p. 77.
Some Microbiological Observations on the Antibiotic-Fed Chick1-2 J. McN.
SIEBURTH, 3 J. J. JEZESKI, E. G. HILL 4 AND L. E. CARPENTER 5
School of Veterinary Medicine and Departments of Dairy and Poultry Husbandry and the Hormel Institute, University of Minnesota, St. Paul 1, Minnesota (Received for publication October 26. 1953)
M
ANY growth studies dealing with antibiotic supplementation have included limited bacteriological studies in an endeavor to elucidate the mechanism of growth promotion. Sieburth et al. (1951) found no consistent and reproducible modification of the cecal microflora by low growth-promoting levels of penicillin and terramycin fed to turkey poults over a four week period. Rosenberg et al. (1952) also failed to show a modification of the fecal microflora of chicks fed diets supplemented with five progressively doubled 1 Paper No. 3055, Scientific Journal Series, Minnesota Agricultural Experiment Station. 2 This research was supported in part by funds furnished by Lederle Laboratories and the American Feed Manufacturers Association. 3 Hormel Institute Research Fellow. 4 Present address, Hormel Institute, University of Minnesota, Austin, Minnesota. 6 Present address, Distillers Feed Research Council, Inc., Cincinnati 2, Ohio.
concentrations of terramycin. However, other reports have indicated that the cecal and fecal microflora are significantly altered by antibiotic supplementation of the feed. March and Biely (1952) reported that aureomycin supplementation caused a consistent lowering of the population of lactobacilli of the feces during the five week experimental period. On the other hand, Anderson, Cunningham and Slinger (1952) on the basis of counts made at ten weeks of age, reported an increase in most groups including the lactobacilli in the cecal contents of birds fed penicillinsupplemented diets. The counts obtained of the cecal and fecal microflora are very variable and may not necessarily reflect changes in other segments of the intestinal tract. This is indicated by Cook et al. (1952) who found that the counts of lactobacilli in the gizzard and cecum of turkey poults fed a
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Brody, S., 1927. Growth and development. Research Bull. 97, University of Missouri. Brown, P. B., D. E. Becker, S. W. Terrill and L. E. Card, 1952. The effect of aureomycin on the growth and metabolism of the pig. Arch. Biochem. Biophys. 41: 378-382. Coates, M. E., C. D. Dickinson, G. F. Harrison, S. K. Kon, J. W. G. Porter, S. H. Cummins and W. F. J. Cuthbertson, 1952. A mode of action of antibiotics in chick nutrition. J. Sci. Food Agric. 1:43-18. Davis, R. L., and G. M. Briggs, 1951. Studies with antibiotics in chick and poult starting rations. Poultry Sci. 30: 767-771. Scott, H. M., and W. A. Glista, 1950. The effect of
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