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

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

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

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

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”

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…

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

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

Department of Animal Science

Search Parameters

• Databases used:

• Pubmed

• Sciencedirect

• Web of Science

• CAB Abstracts

• Agricola

• Searched all years for initial search

Department of Animal Science

Search ParametersCategory 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

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

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)

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

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

Nu

mb

er o

f pu

bli

cati

on

s

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

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)

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

Department of Animal Science

EFFICACY OF AGP

ALTERNATIVES

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

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)

% O

utc

om

es M

ort

alit

y

0 - +

34.1

10.5

37.4

49.8

71.1

46.9

3.2 3.712.9 18.4 12.1

Overall (n=311) AB+ (n=38) AB- (n=273)

% O

utc

om

es A

DF

I

nr 0 - +

3.2 3.7

55.3 68.4 53.5

1.6 1.8

39.931.6

41.0

Overall (n=311) AB+ (n=38) AB- (n=273)

% O

utc

om

es A

DG

nr 0 - +

30.2

10.5

33.0

43.171.1

39.2

1.0 1.1

25.7 18.426.7

Overall (n=311) AB+ (n=38) AB- (n=273)

% O

utc

om

es G

:F

nr 0 - +

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

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

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)

% O

utc

om

es M

ort

alit

y

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)

% O

utc

om

es A

DF

I

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)

% O

utc

om

es A

DG

nr 0 - +

8.6 4.9 10.4

71.5 80.2 64.5

0.50.3

0.7

19.4 14.624.4

Overall (n=613) AB+ (n=288) AB- (n=299)

% O

utc

om

es G

:F

nr 0 - +

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

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)

% O

utc

om

es M

ort

alit

y

0 - +

15.22.4

18.8

67.176.8

64.2

3.5 1.24.3

14.3 19.6 12.8

Overall (n=2019) AB+ (n=495) AB- (n=1471)

% O

utc

om

es A

DF

I

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)

% O

utc

om

es A

DG

nr 0 - +

17.84.8

21.8

63.2 82.057.3

1.81.0

2.0

17.2 12.1 19.0

Overall (n=2019) AB+ (n=495) AB- (n=1471)

% O

utc

om

es G

:F

nr 0 - +

Department of Animal Science

AGP alternatives excluding Zn/Cu

9.6

2.9

11.0

0.20.32.5

1.4

2.6

Overall (n=1406) AB+ (n=207) AB- (n=1172)

% O

utc

om

es M

ort

alit

y

0 - +

19.73.9

22.2

65.683.1

62.7

4.6 2.4 5.010.1 10.6 10.1

Overall (n=1406) AB+ (n=207) AB- (n=1172)

% O

utc

om

es A

DF

I

nr 0 - +

2.2 2.6

69.382.6

66.7

4.63.9

4.6

24.013.5

26.1

Overall (n=1406) AB+ (n=207) AB- (n=1172)

% O

utc

om

es A

DG

nr 0 - +

21.84.8

24.7

59.584.5

55.5

2.41.9

2.3

16.28.7

17.6

Overall (n=1406) AB+ (n=207) AB- (n=1172)

% O

utc

om

es G

:F

nr 0 - +

Department of Animal Science

AGP alternatives +/- specialty proteins

4.1

10.1

2.0 2.55.2

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-

% O

utc

om

es M

ort

alit

y

0 - +

5.122.2

1.4 3.5 7.126.4

72.0

63.7

76.7 77.3 69.6

60.6

3.73.4

1.7 0.5 4.74.019.2 10.7

20.3 18.7 18.79.0

SP+ SP- AB+SP+ AB+SP- AB-SP+ AB-SP-

% O

utc

om

es A

DF

I

nr 0 - +

0.3 2.8 0.0 0.0 0.5 3.4

64.6 67.6 67.9 74.262.9

66.1

3.72.9 2.0

2.04.5

3.1

31.4 26.7 30.1 23.7 32.1 27.4

SP+ SP- AB+SP+ AB+SP- AB-SP+ AB-SP-

% O

utc

om

es A

DG

nr 0 - +

9.423.9

5.4 3.5 11.428.5

70.358.3

79.7 85.9 65.552.0

2.3 1.3 0.71.5

3.1 1.218.1 16.5 14.2 9.1

20.0 18.2

SP+ SP- AB+SP+ AB+SP- AB-SP+ AB-SP-

% O

utc

om

es G

:F

nr 0 - +

Department of Animal Science

ADDITIONAL USES FOR

DATABASE

Department of Animal Science

DFM - ADG

Resp. # studiesStart 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

Department of Animal Science

All AB alternatives - ADG

Resp. # studiesStart 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

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

Nu

mb

er o

f tr

ials

Pigs/pen

Pig/pen distribution for improved ADG response

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

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

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

Department of Animal Science

• Database available at:

http://www.pork.org/production-topics/animal-science/

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

Department of Animal Science

QUESTIONS?