V2, Department of Animal Science
Research Report AL-1975-12
TREATMENT OF SALMONELLA INFECTION OF SWINE AS INFLUENCED
BY PRIOR SUBTHERAPEUTIC DRUG FEEDING1
H. D. Wallace, H. J. Monegue, K. L. Bryant, H. N. Becker,
S. M. Abrams, N. D. Thanh and G. E. Combs2
The use of feed fortified with antibiotic and other growth promoting drugs
is common practice in swine production. The value of these drugs for the improve-
ment of rate and efficiency of gain is generally acknowledged. However, questions
have been raised concerning the influence of feeding subtherapeutic levels of
drugs on subsequent therapeutic treatment of disease outbreaks. This study was
undertaken to determine whether the treatment of an enteric Salmonella infection
was affected by prior feeding of drugs.
Forty healthy, conventionally raised pigs, 4 weeks of age and averaging
approximately 17 lb. initially were divided into four similar groups according
to weight, sex and litter.
The experimental design was as follows:
(1st 21 davs)
A 10 No antibacterial Infected with No treatment
fortification S. Choleraesuis
B 10 No antibacterial Neomycin1
C 10 CSP-250 (5 Ib/ton) No treatment
D 10 CSP-250 (5 Ib/ton) Neomycin'
1 For 4 consecutive days a water dispersible form of neomycin was provided in
the drinking water at a level calculated to provide 7 mg neomycin base per
kilogram body weight per day per pig.
1 Data from swine unit experiment No. 241. Supported in part by a grant from
Diamond Shamrock Chemical Co., Harrison, New Jersey.
2 Wallace and Combs, Animal Nutritionists and Monegue, Bryant, Abrams and Thanh,
graduate students, Animal Science Department; Becker, Associate Veterinarian,
College of Veterinary Medicine, University of Florida.
This public document was promulgated at an annual cost of
$120.00, or .04 cents per copy to inform county agricul-
tural directors, ranchers and growers of research results
in swine management and nutrition.
Department of Animal Science
Institute of Food and Agricultural Sciences
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Composition of the basic feed mixtures involved is presented in Table 1.
Table 1. Composition of Feed Mixtures
No antibacterial Antibacterial
Ingredients subtherapy subtherapy
Ground yellow corn 62.05 61.80
Soybean oilmeal (49%) 27.00 27.00
Cane sugar 5.00 5.00
Stabilized lard 3.00 3.00
Dynafos (IMCC)1 1.70 1.70
Ground limestone 0.80 0.80
Iodized salt 0.25 0.25
Trace minerals (CCC)2 0.10 0.10
Vitamin premix (UF)3 0.10 0.10
1 Product of International Minerals and Chemical Corporation,
2 Supplied by Calcium Carbonate Company, Quincy, Illinois.
Contained 20% zinc, 5.5% manganese, 1.1% copper, 10% iron,
0.15% iodine, 0.10% cobalt and 2% calcium.
3 Contained 6,000 mg.riboflavin, 20,000 mg. niacin, 12,000
mg. pantothenic acid, 80,000 mg. choline chloride, 10,000
mcg. Vitamin B12, 2,500,000 I.U. Vitamin A, 400,000 ICU
Vitamin D3 and 10,000 I.U. Vitamin E per lb. of premix.
4 Each pound of CSP-250 contained 20, 20 and 10 gm. of chlor-
tetracycline, sulfathiazole and penicillin respectively.
This product was supplied by Diamond Shamrock Chemical Co.,
Harrison, New Jersey.
All feeding was ad libitum by self feeder, except during the challenge
period, details of which are explained later. Automatic nipple type waterers
supplied fresh water to each group of pigs. During the post challenge treat-
ment period groups B and D were provided medicated water by trough on demand
Pigs were housed in an enclosed nursery ventilated by window fans. Each
group of pigs was penned in an 8 x 7 ft. wire cage with expanded metal floor.
The cages stood on one-foot high legs over a sloping concrete floor. Wastes
passed through the expanded metal floors onto the concrete from which they
were periodically washed into a central storage pit.
After feeding the pigs as indicated for 21 days the medicated feed (CSP-250)
was withdrawn from Groups C and D and replaced with non-medicated feed for a
period of 1 days prior to challenge. On the 23rd day all four groups of pigs
were challenged with S. Choleraesuis Var Kunzendorf. The strain of organism
(D/S #15) was in the form of an agar sTant and provided by Diamond Shamrock
Chemical Company. A loopful of organism was scraped from the slant and inoculated
with Trypticase Soy Broth and incubated for 4 hours. One ml. of this 4 hour
broth culture was then added to 250 ml. of Trypticase Soy Broth prepared in a
500 ml. flask. Two flasks of Trypticase Soy Broth were required for an adequate
supply of challenge inoculum. The two 500 ml. flasks of inoculum were incubated
for 24 hours. After incubation the two cultures were pooled and the concentra-
tion of the Salmonella organism was determined. Duplicated samples showed an
average concentration of 74 x 107/ml. in the challenge culture. Ten ml. of the
24 hour culture was added per lb. of challenge feed. An abundance of trough space
was provided and each pig was given a 1 lb. feeding of the challenge feed following
a 15 hour feed withholding period. It is estimated that each pig consumed approxi-
mately 750 x 107 salmonella with the 1 lb. of feed. Following challenge all
groups were again offered the non-medicated feed mixture for 1 days, after which
medication was again resumed in the feed mixtures for groups C and D.
Daily rectal temperatures were taken on all pigs during the entire post
challenge period (23-37 days). The temperatures were recorded between 12 noon
and 2 p.m. each day.
The degree of scouring (diarrhea) for each pen of pigs (number of pigs per
pen scouring and severity of scouring) was recorded throughout the experiment
(1 37 days). The following numerical code was used: 1 no scours, 2 mild
scours, 3 moderate scours and 4 severe scours.
Fecal samples were individually collected from all pigs 24 hours post challenge
and processed immediately for Salmonella colonization counting. One gm. of fecal
sample was homogenized in 9 ml. of tetrathionate broth, and 10-fold dilutions were
carried out in the same broth up to a total of 10. Each dilution was plated in
duplicate on the surface of Brilliant Green Sulfa Agar in a volume of 0.1 ml.
After spreading the 0.1 ml. of inoculum, the plates were incubated for 24 hours
at 370 C.
Approximately 72 hours following challenge, Group B and D were treated for
4 consecutive days with water dispersible neomycin. Water intake was estimated
and an attempt was made to provide each pig with 7 mg. of neomycin base per lb.
body weight per day. The neomycin containing water was provided periodically
in troughs throughout the day, more or less on the basis of pig demand.
All pigs that died during the experiment were necropsied. Tissue samples
were taken for Salmonella culture.
Results and Discussion
Daily gain and feed utilization data are summarized in Table 2. Pigs fed a
subtherapeutic level of CSP-250 (Groups C and D) gained significantly faster
(P < .01) and more efficiently during the pre-challenge period. After 23 days
CSP-250 fed pigs averaged 40 lb. compared to 34.8 for control pigs. Much less feed
was required per unit of gain for the medicated pigs. The difference in weight
and general health was readily apparent upon visual examination of the four groups.
Performance of the pigs during the 7-day period from challenge through
neomycin treatment was quite variable. Group A (no CSP-250) withstood this
stress period best, whereas Group B (also no CSP-250) had the most difficult
time. The neomycin treatment did not appear effective as measured by pig
response in terms of improved general health, weight gain or feed utilization,
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Table 2. Pig Performance as Influenced
Feeding, Salmonella Challenge
by Subtherapeutic CSP-250
and Subsequent Treatment
Group A B C D
CSP-250 post challenge medication No No Yes Yes
Challenged with Salmonella Yes Yes Yes Yes
Treated with Neomycin No Yes No Yes
Number of pigs 10 10 10 10
Av. initial wt., lb. 17.3 17.3 17.3 17.3
Av. wt. after 23 da., lb.
(prior to challenge) 35.1 34.5 39.0 41.0
Av. daily gain, lb. 1st 23 da. 0.78 0.75 0:94** 1.04**
Feed/gain, lb. 1st 23 da. 1.97 2.04 1.81 1.76
Av. wt. after 30 da.,lb.
(post challenge and treatment) 41.8 36.52 42.8 44.63
Daily gain, da. 23 to da. 30, lb. 0.96 0.29 0.54 0.50
Feed/gain, lb. da. 23 to da. 30, lb. 1.94 3.89 2.94 3.32
Av. wt. after 37 da., lb. 51.01 43.6 53.1 56.9
Daily gain,da. 30 to da. 37, lb. 1.31 1.03 1.48 1.76
Feed/gain, lb. da. 30 to da. 37, lb. 2.02 1.91 1.83 1.65
** Gained significantly faster than groups A or B (P < .01).
1 One pig died on 33rd day.
2 One pig died on 27th day and one on 30th day.
3 One pig died on 29th day.
Performance from day 30 to day 37 again favored Group C and D which were on.
a subtherapeutic level of CSP-250. At the termination of the experiment
surviving pigs in these two groups (19 in number) weighed an'average of 54.9 lb.
compared to 47.5 lb. for those in Groups A and B (17 surviving). The'general
health and appearance of pigs in Groups C and D seemed markedly superior. 'All
surviving pigs from the experiment quickly returned to good health and gained
normally to market weight.
Salmonella cultures of the fecal samples collected 24 hour post challenge
were negative. Since the pigs were quite sick at the time of sampling this
result was surprising. However, it was assumed that samples were collected too
soon after challenge. To verify this, an ill pig was sampled 72 hr. post challenge
and the culture showed 88 x 104 salmonella per gm. feces.
Individual daily rectal temperatures were recorded for all pigs commencing
the day of challenge through 14 days post challenge. .These are shown in graphic
form in Figure 1. Temperatures were first measured 6 hr. after challenge and
there was some indication that temperatures had already begun to increase.
Generally temperatures for all groups peaked during days 3 and.4 post challenge.
This coincided with obvious illness of the pigs. There were no marked differences
between groups. Group B showed somewhat higher maximum temperatures and also
appeared somewhat sicker than the other groups. All groups were obviously ill
within 12 hr. post challenge. They piled up, some shivered and -all showed marked
listlessness. The listlessness became even more intense during days 2, 3, 4 and
5 post challenge. Body temperatures generally progressed downward after day 3-
post challenge but were not considered as back to normal until about 12 days post
challenge. By this time pigs in all groups had regained a healthy appearance and
seemed totally recovered. There was no clear indication that the neomycin treat-
ment influenced body temperature data or the recovery of the pigs.
Individual daily scouring indexes were recorded for all pigs for the entire
duration of the experiment. In general pigs were not afflicted with severe
diarrhea during the experiment. There was a significant incidence of scours in
all groups coincident with the Salmonella infection. However, the striking
effect was the bloody nature of the stools, not always associated with diarrhea.
Some pigs in all groups passed blood in the stools. The blood likely entered the
digestive tract from the lower bowel since it was usually fresh and bright in
color. The four pigs that died were all afflicted with this syndrome prior to
death. Post mortem findings on the four pigs were similar: pale musculature,
thin and watery blood, flabby heart, pale liver, enlarged and congested spleen,
stomach empty and mucosa slightly reddened, small intestine normal but mesenteric
lymph nodes were swollen and edematous, colon and cecum contained solid feces
but blood was present in the terminal colon and rectum, lungs were free of
pneumonia but were edematous, and kidneys contained petechial hemorrhages.
Salmonella Cholerasuis Var Kunzendorf was isolated from cultures of the tissues
of small intestine, colon and mesenteric lymph nodes.
The thin watery blood syndrome did not fit the typical picture for salmonellosis.
Corn used in the study contained a fairly high level of aflatoxin which tends to
increase blood clotting time. It is assumed that the combined damage caused by
the Salmonella organisms in conjunction with the aflatoxicosis resulted in excessive
blood loss into the feces and contributed in large measure to the death of the pigs.
A study, involving 40 weanling pigs, was conducted to determine the influence
of prior feeding of subtherapeutic drugs (combination of chlortetracycline, sulfa-
thiazole and penicillin) on the therapeutic treatment of an induced Salmonella
During the 3-week feeding period prior to challenge pigs fed the drugs
gained significantly faster and more efficiently than control pigs given no drugs.
At the time of challenge the two pens of pigs fed drugs averaged approximately
5 lb. per pig heavier than the controls.
Pigs in all pens became ill within 12 hr. after challenge as indicated by a
rise in body temperatures and a tendency toward listlessness. Body temperatures
peaked at between 1060 and 1080 F on days 3 and 4 post challenge. No significant
differences in body temperatures between pens was observed.
Treatment with water dispersible neomycin did not appear to speed recovery,
regardless of the prior feeding regime.
During the period of infection some scouring and manure with fresh blood
were observed in all pens. Four pigs died during the experiment. Post mortem
findings were highlighted by pale musculature and thin watery blood. Salmonella
Cholerasuis Var Kunzendorf was isolated from tissue cultures of the small
intestines, colon and mesenteric lymph nodes.
The experiment demonstrated that prior subtherapeutic feeding of CSP-250 made
it possible for pigs to withstand an enteric infection of Salmonella somewhat
better. No evidence was obtained that subtherapeutic feeding of CSP-250 made
treatment with neomycin less effective.
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