Growth Promotion Alternatives to Sub-Therapeutic Antibiotics - Wes Schweer, from the 2017 Allen D. Leman Swine Conference, September 16-19, 2017, St. Paul, Minnesota, USA. More presentations at http://www.swinecast.com/2017-leman-swine-conference-material

1. Department of Animal Science
Department of Animal Science
A review and evaluation of growth
promoting antibiotic alternatives in
the literature
Wes Schweer
Ph.D. Candidate
Allen D. Leman Conference September 18, 2017

2. Department of Animal Science
Project Team for the National Pork Board
Funded Project
• Iowa State University
• PI: Nicholas Gabler (AnS)
• John Patience (AnS)
• Kent Schwartz (VDL)
• Chris Rademacher (VDPAM)
• Alex Ramirez (VDPAM)
• Daniel Linhares (VDPAM)
• Kristin Olsen (AnS)
• USDA-NADC
• Heather Allen
• Crystal Loving

3. Department of Animal Science
Antibiotic growth promotants (AGPs)
• Used in livestock industry for 50+ years
• Growth promotion or improved nutritional efficiency
• Increasing feed efficiency 3%
• Improving growth rates 3-8%
• How AGPs improve performance not fully understood
• Antibiotic growth
promoters (AGPs)
• Administered at a low,
sub-therapeutic dose

4. Department of Animal Science
Potential implications of antimicrobials on
animal physiology
• Optimal animal health depends
on host and microbial attributes
• AGPs have
1) Indirect effects through
the microbiota
2) Direct effects on the host
• The functional and interactive
effects of AGPs on the host and
the microbiota are less clear
International Journal of Antimicrobial Agents, Volume
49, Issue 1, 2017, 12–24
http://dx.doi.org/10.1016/j.ijantimicag.2016.08.006

5. Department of Animal Science
Veterinary Feed Directive - FDA
• “Production uses” (growth promotion and nutritional
efficiency) of antibiotics in classes used in human
medicine are injudicious
• Requires the use of these classes of antibiotics be under
veterinary oversight
• Just cause for use or “Judicious use”

6. Department of Animal Science
Are there AGP alternatives?
• Need for evaluation of AGP alternative products
• Sub-therapeutic not therapeutic antibiotic alternatives
• Thousands of AGP alternative studies with several
different parameters measured
• Few parameters consistently measured across studies
• What and why did studies work?
• Replication
• Pen size
• Base diet
• Study duration, etc…

7. Department of Animal Science
Project Objectives
• Evaluate the literature to assess dietary alternatives to
sub-therapeutic antibiotics
• Examine trends and relationships of the efficacy of
these AGP alternatives to improve pig performance
and reduce mortality

8. Department of Animal Science
Literature Review criteria
• Identified AGP alternatives currently used
• Papers from 1990-present (January 1, 2017)
• Mention of performance or mortality in abstract
• Must be peer reviewed, original research articles
• No review articles, conference proceedings
• Must be in English
• Primarily interested in nursery trials, but sow and
finisher trials not excluded

9. Department of Animal Science
Search Parameters
• Databases used:
• Pubmed
• Sciencedirect
• Web of Science
• CAB Abstracts
• Agricola
• Searched all years for initial search

10. Department of Animal Science
Search Parameters
Category Search Term
Probiotic probiotic AND swine (pig)
Prebiotic prebiotic AND swine
Oligosaccharide oligosaccharide AND swine AND wean
Organic Acids ((“organic acid”) OR (“organic acids”) AND swine
Essential oils /
botanicals /
plant extracts
essential oil AND swine
botanical AND swine
plant extract AND swine AND wean
Yeast yeast AND swine AND wean
Resistant starch/
fiber
starch AND swine AND wean
fiber AND swine AND wean
Zinc/Copper zinc AND swine AND wean
copper AND swine AND wean
Lysozyme lysozyme AND swine

11. Department of Animal Science
Search term into database
Remove duplicates, keep only original, peer reviewed journal
articles since 1990
Exclude articles that did not contain performance or mortality
data in abstract
Keep articles in English with full text available

12. Department of Animal Science
Publication Criteria
• Challenge (yes/no)
• number/treatment
• Experimental Unit
• Pigs/pen
• Age of pig (days)
• Start BW (kg)
• Genetics
• Duration of study (days)
• AGPs (yes/no)
• Diet components
• ADG (-,0,+)*
• ADFI (-,0,+)*
• Feed Efficiency (-,0,+)*
• Mortality (-,0,+)*
• Blood Assay (yes/no)
• Tissue Assay (yes/no)
• Microbiome (yes/no)
• Specialty proteins (yes/no)
* P < 0.05 (statistically significant)

13. Department of Animal Science
Publication Criteria
• If publication included control and multiple treatments,
each treatment considered one trial
• Example:
• Treatments: control, butyric acid, propionic acid,
butyric + propionic acid
• Publication would include 3 trials
• Data compiled in Excel spreadsheet
• Used to determine trends or patterns within each
parameter

14. Department of Animal Science
Publications reviewed
23,752
14,230
1,312 1,050 830
-
5,000
10,000
15,000
20,000
25,000
Total After duplicates
+ since 1990
Usable Articles
available
Open access
publications at
Iowa State
Numberofpublications

15. Department of Animal Science
Direct Fed Microbials (DFM/Probiotics)
• Search term: probiotic AND swine
• Total articles: 3,550
• After duplicates + since 1990: 2,555
• Contain performance/mortality: 314
• Articles available: 243
• Accessible articles: 189

16. Department of Animal Science
DFM
• 311 total trials
• 46 challenge trials
• Avg. n/trt: 21.0
• Avg. pigs/pen: 6.0
• Avg. study duration: 36.6 days
• Avg. age: 24.0 days
• Avg. BW: 14.1 kg
• Probiotic type: Bacillus (49), Bifidobacterium (27),
Enterococcus (37), Lactobacillus (62), combo (87)

17. Department of Animal Science
Reported Antibiotic Use
• 2019 total trials
• 24.5% used AB in base diet
• 72.9% no AB in base diet
• Commonly used antibiotics
• Tylosin
• Chlorotetracycline
• Oxytetracycline
• Colistin
• Carbadox

18. Department of Animal Science
EFFICACY OF AGP
ALTERNATIVES

19. Department of Animal Science
Direct-Fed Microbial (Probiotic)
• Live microbial feed supplements that can survive in GIT
• Three common categories:
• Bacillus
• Lactic acid-producing bacteria
• Ex. Lactobacillus, Bifidobacterium, Enterococcus
• Yeast

20. Department of Animal Science
Direct-Fed Microbial
9.0 7.9 9.2
4.8 7.9 4.4
Overall (n=311) AB+ (n=38) AB- (n=273)
%OutcomesMortality
0 - +
34.1
10.5
37.4
49.8
71.1
46.9
3.2 3.7
12.9 18.4 12.1
Overall (n=311) AB+ (n=38) AB- (n=273)
%OutcomesADFI
nr 0 - +
3.2 3.7
55.3 68.4 53.5
1.6 1.8
39.9 31.6
41.0
Overall (n=311) AB+ (n=38) AB- (n=273)
%OutcomesADG
nr 0 - +
30.2
10.5
33.0
43.1
71.1
39.2
1.0 1.1
25.7 18.4 26.7
Overall (n=311) AB+ (n=38) AB- (n=273)
%OutcomesG:F
nr 0 - +

21. Department of Animal Science
DFM - Observations
• 124 trials improved ADG:
• 37 probiotic combination – no distinct patterns
• 30 Lactobacillus spp.
• 8/30 = Lactobacillus plantarum
• 20 Bacillus spp.
• 17 Enterococcus spp.
• 16/17 = Enterococcus faecium

22. Department of Animal Science
Zinc/Copper
• Zinc (Zn) and Copper (Cu) – essential trace mineral
• Zn recommended dietary level = 100 ppm
• Pharmacological levels effective (up to 3000 ppm)
• Exact mode of action not known
• Reduces/prevents post weaning diarrhea
• Increased antimicrobial peptides in small intestine
• Reduced Gram-positive bacteria

23. Department of Animal Science
Zn/Cu
1.8 1.7 2.0
1.8
0.7
1.3
Overall (n=613) AB+ (n=288) AB- (n=299)
%OutcomesMortality
0 - +
4.7 1.4 5.4
70.5 72.2 69.9
0.8 0.3 1.3
24.0 26.0 23.4
Overall (n=613) AB+ (n=288) AB- (n=299)
%OutcomesADFI
nr 0 - +
0.5 1.0
60.4 61.8 57.5
0.5 0.7
38.7 37.5 41.5
Overall (n=613) AB+ (n=288) AB- (n=299)
%OutcomesADG
nr 0 - +
8.6 4.9 10.4
71.5 80.2 64.5
0.5
0.3
0.7
19.4 14.6
24.4
Overall (n=613) AB+ (n=288) AB- (n=299)
%OutcomesG:F
nr 0 - +

24. Department of Animal Science
Trends – Zn/Cu
• 243 trials improved ADG:
• 73 Cu only
• 13, 125 ppm
• 13, 200 ppm
• 15, 250 ppm
• 154 Zn only
• 27, 3000 ppm
• 17, 2500 ppm
• 16, 100 ppm
• 11, 1500 ppm
• 12 Zn+Cu
• 4, 3000/100 ppm
• 4, 3000/250 ppm
• 2, 3000/125 ppm

25. Department of Animal Science
All AGP alternatives
7.2
2.2
9.2
0.1
0.22.3
1.0
2.4
Overall (n=2019) AB+ (n=495) AB- (n=1471)
%OutcomesMortality
0 - +
15.2
2.4
18.8
67.1
76.8
64.2
3.5 1.2
4.3
14.3 19.6 12.8
Overall (n=2019) AB+ (n=495) AB- (n=1471)
%OutcomesADFI
nr 0 - +
1.7 2.2
66.6 70.5 64.9
3.3 2.0 3.7
28.4 27.5 29.2
Overall (n=2019) AB+ (n=495) AB- (n=1471)
%OutcomesADG
nr 0 - +
17.8
4.8
21.8
63.2 82.0 57.3
1.8
1.0
2.0
17.2 12.1 19.0
Overall (n=2019) AB+ (n=495) AB- (n=1471)
%OutcomesG:F
nr 0 - +

26. Department of Animal Science
AGP alternatives excluding Zn/Cu
9.6
2.9
11.0
0.2
0.32.5
1.4
2.6
Overall (n=1406) AB+ (n=207) AB- (n=1172)
%OutcomesMortality
0 - +
19.7
3.9
22.2
65.6
83.1
62.7
4.6 2.4 5.0
10.1 10.6 10.1
Overall (n=1406) AB+ (n=207) AB- (n=1172)
%OutcomesADFI
nr 0 - +
2.2 2.6
69.3 82.6
66.7
4.6
3.9
4.6
24.0
13.5
26.1
Overall (n=1406) AB+ (n=207) AB- (n=1172)
%OutcomesADG
nr 0 - +
21.8
4.8
24.7
59.5 84.5
55.5
2.4
1.9
2.3
16.2
8.7
17.6
Overall (n=1406) AB+ (n=207) AB- (n=1172)
%OutcomesG:F
nr 0 - +

27. Department of Animal Science
AGP alternatives +/- specialty proteins
4.1
10.1
2.0 2.5
5.2
11.8
0.1
0.2
0.2
0.2
2.3
1.8
1.0 1.0
2.9
2.0
SP+ SP- AB+SP+ AB+SP- AB-SP+ AB-SP-
%OutcomesMortality
0 - +
5.1
22.2
1.4 3.5 7.1
26.4
72.0
63.7
76.7 77.3 69.6
60.6
3.7
3.4
1.7 0.5 4.7
4.019.2 10.7 20.3 18.7 18.7
9.0
SP+ SP- AB+SP+ AB+SP- AB-SP+ AB-SP-
%OutcomesADFI
nr 0 - +
0.3 2.8 0.0 0.0 0.5 3.4
64.6 67.6 67.9 74.2
62.9 66.1
3.7
2.9 2.0
2.0
4.5
3.1
31.4 26.7 30.1 23.7 32.1 27.4
SP+ SP- AB+SP+ AB+SP- AB-SP+ AB-SP-
%OutcomesADG
nr 0 - +
9.4
23.9
5.4 3.5 11.4
28.5
70.3
58.3
79.7 85.9 65.5
52.0
2.3 1.3 0.7
1.5
3.1 1.2
18.1 16.5 14.2 9.1
20.0 18.2
SP+ SP- AB+SP+ AB+SP- AB-SP+ AB-SP-
%OutcomesG:F
nr 0 - +

28. Department of Animal Science
ADDITIONAL USES FOR
DATABASE

29. Department of Animal Science
DFM - ADG
Resp. # studies
Start BW
(kg)
Duration
(days)
Age
(days)
(0) 172 15.1 29.6 23.9
(-) 5 25.7 28.0 44.2
(+) 124 12.8 47.3 23.6
nr 10 5.0 26.2 17.3
Total 311
Resp. n/trt Pig/pen
Avg Min Max Med Stdev Avg Min Max Med Stdev
(0) 14.6 2 400 8.0 32.5 4.9 1 22 4.0 4.2
(-) 14.0 12 16 15.0 1.7 5.8 1 14 4.0 4.9
(+) 18.3 2 600 6.0 57.9 7.2 1 35 6.0 5.6
nr 165.5 2 1471 10.0 436.2 8.4 1 11 10.5 4.0
No change in
growth
Negative impact on
growth
Positive impact on
growth
Not reported

30. Department of Animal Science
All AB alternatives - ADG
Resp. # studies
Start BW
(kg)
Duration
(days)
Age
(days)
0 1344 10.5 32.5 24.1
(-) 67 13.2 33.9 30.8
(+) 574 10.1 38.0 23.6
nr 34 17.6 19.2 30.5
Total 2019
Resp. n/trt Pig/pen
Avg Min Max Med Stdev Avg Min Max Med Stdev
(0) 11.7 1 400 7.0 19.4 4.8 1 34 4.0 4.3
(-) 8.0 2 32 6.0 5.3 3.6 1 14 4.0 3.0
(+) 12.8 1 600 6.0 33.6 6.7 1 37 5.0 5.4
nr 55.9 2 1471 11.0 246.9 5.2 1 24 1.0 5.5

31. Department of Animal Science
0
50
100
150
200
250
300
350
400
1 to 1 2 to 2 3 to 9 10 to 12 13 to 20 21 to 5000 nr
Numberoftrials
Pigs/pen
Pig/pen distribution for improved ADG response

32. Department of Animal Science
Conclusions
• ~30% of AGP alternatives improve growth performance
• DFM – 39.9%
• Zn/Cu – 39.2%
• Organic Acids – 31.2%
• Efficacy of AGP alternatives reduced when AB used in
basal diet
• AB alter gut microbial profile

33. Department of Animal Science
Conclusions
• Database is an effective tool to predict trends on pen
size, pig age and weight, and feeding duration to
evaluate AGP alternative products
• Develop a protocol that defines critical and essential
components that can be used in AGP alternative studies

34. Department of Animal Science
Outcomes
• This project will recommend
• Necessary parameters that should be recorded and at which times
• Recommendations on project design to best translate smaller scaled
research to the industry
• n/trt, n/pen
• Useful parameters to (or not) measure that may relate to altered pig
performance/mortality
• This project will not recommend
• The best AGP alternatives to use
• Genetic background and health status to best evaluate on

35. Department of Animal Science
• Database available at:
http://www.pork.org/production-topics/animal-science/

36. Department of Animal Science
Acknowledgements
• Funding – National Pork Board
• Iowa State University
• Nicholas Gabler (AnS)
• John Patience (AnS)
• Kent Schwartz (VDL)
• Chris Rademacher (VDPAM)
• Alex Ramirez (VDPAM)
• Daniel Linhares (VDPAM)
• Kristin Olsen (AnS)
• USDA-NADC
• Heather Allen
• Crystal Loving
• Gabler Lab
• Shelby Curry
• Erin Lewis
• Juli Jespersen
• Brett Barthman

37. Department of Animal Science
QUESTIONS?