Pre congreso qualivet diamondv wael abdelrahman strategies for controlling the risk of antibiotic re

Strategies for Controlling the Risk of Antibiotic Resistance in Poultry Wael Abdelrahman DVM, PhD Poultry Technical Service & Business Development Manager – Europe Diamond V

Ponencia patrocinada por:

Wael Abdelrahman DVM, PhD, Poultry Technical Service & Business Development Manager – Europe.

Diamond V Especialidad en salud y patología avícola aves de corral y aditivos para piensos. Doctor en patologías avícolas por la Universidad de Londres, Reino Unido; DVM en Medicina Veterinaria por la Universidad de Canal de Suez, Egipto.

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Take Home Message 1. Antibiotic resistance is a real issue 2. No single solution, be critical of all interventions

3. There is a technology that can reduce the antibiotic resistance in pathogens

The Golden Age of Antibiotics Is OVER!

Alexander Fleming discovered Penicillin in 1928.

Awarded Nobel Prize in 1945.

Antibiotics are: • Natural products • Natural products that have been chemically modified [semi synthetic] • Synthetic chemicals Topp, 2015. Midwest ASAS Meeting.

Infec&ous diseases – Age standardised mortality rate (per 100,000), 1911-­‐2005 (Scotland's Popula&on 2005: The Registrar General's Annual Review of Demographic Trends: 151st Edi&on hLp://www.gro-­‐scotland.gov.uk)

Polar bears in Svalbard, Norway and antibiotic resistance

Antibiotic Mode of Action on Bacteria

Antibiotics Resistance Mechanisms

Antibiotic Resistance Develops Rapidly sulfonamides

methicillin

penicillin G

expanded-­‐spectrum cephalosporins

streptomycin tetracycline

augmen&n

erythromycin

norfloxacin

nalidixic acid linezolid

vancomycin

1930

1940

1950

1960

Davies, Mobashery; via Wright

1970

1980

1990

2000

European antibiotic resistance levels in poultry – E.coli EFSA 2014 An&bio&c

Resistance % Broilers (27) 58.6

Turkeys (11) 69.0

6.7

3.2

Cefotaxime

5.1

2.3

Ce\azidime

5.0

2.2

Chloramphenicol

21.6

26.5

Ciprofloxacin

65.7

50.3

Colis&n

0.9

7.4

Gentamicin

11.6

10.0

Nalidixic acid

62.6

43.5

Sulfamethoxazole

53.1

51.1

Tetracycline

50.1

70.9

Ampicillin Azithromycin

European antibiotic resistance levels in poultry – Salmonella EFSA 2014 An&bio&c

Resistance % Broilers (22) 19.1

Broiler breeders (4) 14.1

Turkeys (9) 58.0

Layers (15) 8.8

Azithromycin

1.9

NA

1.5

0.4

Cefotaxime

2.3

1.9

0

0.4

Ce\azidime

2.6

NA

0

0.4

Chloramphenicol

4.0

3.2

10.6

1.4

Ciprofloxacin

53.5

12.2

65.8

15.9

Colis&n

8.3

13.5

1.8

10.5

Gentamicin

6.6

3.2

7.7

1.5

Nalidixic acid

48.7

9.6

43.7

14.4

Sulfamethoxazole

45.1

13.5

50.4

10.6

Tetracycline

40.4

19.9

68.3

11.4

Ampicillin

European antibiotic resistance levels in poultry – Campylobacter EFSA 2014 AnCbioCc

Resistance % Broilers

Turkeys

C jejuni (25)

C. Coli (8)

C jejuni (10)

C. Coli (3)

Ciprofloxacin

69.8

74.3

69.6

94.4

Erythromycin

5.9

14.5

2.5

43.3

Gentamicin

0.9

2.6

0.3

3.6

Nalidixic acid

65.1

69.5

63.2

90.3

Streptomycin Tetracycline

6.9 54.4

22.0 59.6

4.1 65.4

30.8 89.7

Judicious (Responsible) Antibiotic Use • Today’s Application • Prevention (not an option in the EU, South Korea, Japan, etc.)

• Therapy (treatment) • No longer an option • Medically important antibiotics • Growth promotion • Use without veterinary prescription • The right drug, at the right time, at the right dose

Challenges Consumer & Government Regulation

Producer

Safe & Good Quality Food

Optimum Performance Healthy Livestock

Â

No antibiotics No residues No antibiotic resistance Â

AGPs/antibiotics/ionophores

Challenges Producer concerns with removing antibiotics: • Decreased productivity • Increased morbidity and mortality • Increased cost of managing healthy flock • Increased disease incidence

Consistent loss of profitability!!

Disease Control Triangle Vaccination, , Medication, Feed Additives

Controlling Sources of Infection & Risk Factors

BIOSECURITY

Animal Health

Public Health

Antibiotic Stewardship

Immune Strength For Life™

Production Efficiency

Immune Support Products strengthening the immune system for optimal health & wellness.

On-Farm Food Safety

Feed Additives & Immune Modulators • Most feed additives used for intestinal/gut health • How to define intestinal health?

• What is the feed additive doing for you animals?

• Identify technologies that impact animal health • Reduce the exposure or exclude pathogens • Improve intestinal integrity • Support innate and adaptive immune function

New Regulations Require A New Strategy A new strategy: • Strengthen the immune system • Support digestive tissue integrity • Promote healthy microbial balance

Results in: ü Pathogen load reduction ü Antibiotic resistance reduction

XPC™ Reduces Salmonella Antibiotic Resistance in Poultry K. M. Feye1, K. L. Anderson1, M. F. Scott2, D. R. McIntyre2 and S. A. Carlson1

1. Iowa State University, Ames, IA, USA 2. Diamond V, Cedar Rapids, IA, USA

Experimental Design

Replicated 3 Times Feye et al., 2016

Salmonella Fecal Shedding: Summary Feeding XPC reduced fecal shedding

a,bP < 0.05

Feye et al., 2016

Intestinal Colonization: Summary Feeding XPC decreased intestinal colonization

29,023 CFU/g CONa a,bP < 0.05

Feye et al., 2016

3,875 CFU/g XPCb

Antibiotic Resistance of Salmonella: Summary Feeding XPC reduced antibiotic resistance

a,bP < 0.05

Feye et al., 2016

Salmonella Antibiotic Resistance

• Salmonella DNA contains an integron • Integron contain genes for antibiotic resistance • Loss of the integron = Loss of Antibiotic Resistance • Presence or absence of integron is measurable

Feye et al., 2016

Antibiotic Resistance of Salmonella: Summary Antibiotic resistance was due to the loss of the integron.

a,bP < 0.05

Feye et al., 2016

Commercial Poultry Trials Combined Results

Materials & Methods • Commercial poultry field trials with matched houses/farms • Natural Salmonella field challenge • Two Feed Treatments 1. CON diet: standard company diet 2. CON diet + XPC at 1.25 kg/MT from DOC to market

• Ceca sampling preferred method for meat birds • Cloaca sampling preferred method for layers • • • •

24 Companies Reported 318 barns 15,106 samples 34,262 colonies tested for ABX resistance

Commercial Field Evaluation XPC Reduces Salmonella Prevalence vs. Control

% Reduction from Control

0,0

Broilers

Turkeys

-­‐20,0

-­‐40,0

-­‐60,0

-­‐80,0

-­‐100,0

N = 15,106 samples

Avg. = 56.5% Reduction Field Trials: AL, AR, CA, GA, IA, IN, ME, MN, MO, NC, OH, SC, SD, TX, VA

Layers

In Commercial Field Evaluations XPC Reduces Salmonella Numbers (CFU/g) vs. Control

% Reduction from Control

0,0

Broilers

Turkeys

-­‐20,0

-­‐40,0

-­‐60,0

-­‐80,0

-­‐100,0

N = 15,106 samples

Avg. = 88.0% Reduction Field Trials: AL, AR, CA, GA, IA, IN, ME, MN, MO, NC, OH, SC, SD, TX, VA

Layers

Effects of XPCTM on Salmonella Prevalence, Numbers and Antibiotic Resistance in Ceca Samples Commercial Broilers

© Diamond V, Inc. All rights reserved. This presenta&on is the confiden&al and proprietary property of Diamond V. Diamond V does not give its consent for its distribu&on or license the use of its content.

Materials & Methods Commercial broiler field trials using paired houses/farms 11 different companies • 217 total houses tested • 7,591 individual ceca samples Two Feed Treatments • CON diet: standard company diet • CON diet + XPC at 1.25 kg/tonne from DOC to market Broiler age: 50 d One pair of ceca per bird manually harvested • 50 birds/house after evisceration

Ceca Salmonella: Prevalence & Numbers 200,0

20,0

147.0a 19.4a CFU/g

Prevalence (%)

30,0

10,0

100,0

6.9b 8.0b 0,0

0,0 CON a,bP

CON

XPC

< 0.0001

Broiler Field Samples; n = 7,591

Pavlidis et al., 2016

XPC

Colonies Resistant to Antibiotic (%)

Antibiotic Resistance of Salmonella Recovered from Ceca 30,00

20,00

CON

17.7a 13.6a

10,00

6.5a 1.4a

0.5a

0,00 Florfenicol a,bP

XPC

CeXiofur

< 0.0001

Broiler Field Samples: 21,029 Colonies Tested Pavlidis et al., 2016

0.0a Enrofloxacin

Effects of XPCTM on Salmonella Prevalence, Numbers and Antibiotic Resistance in Ceca Samples Commercial Turkeys

© Diamond V, Inc. All rights reserved. This presenta&on is the confiden&al and proprietary property of Diamond V. Diamond V does not give its consent for its distribu&on or license the use of its content.

Materials & Methods Commercial turkey field trials using paired barns/farms 9 different U.S. based companies • 84 total commercial barns tested • 4,123 individual ceca samples Two Feed Treatments • CON diet: standard company diet • CON diet plus XPC at 1.25 kg/tonne from DOC to market Average age: 139 d One ceca pair per bird manually harvested • 50 birds/house after evisceration

Ceca Salmonella: Prevalence & Numbers 40,0

30,0

30,0 20,0

18.4a CFU/g

Prevalence (%)

27.7a

10,0

7.2b

20,0

10,0 2.0b 0,0

0,0 CON a,bP

CON

XPC

< 0.0001

Turkey Field Samples; n = 4,123

McIntyre et al., 2016

XPC

Colonies Resistant to Antibiotic (%)

Antibiotic Resistance of Salmonella Recovered from Ceca 20,0

CON

14.4a 15,0 10.5a 10,0 5.0a

5,0 1.6b

1.3b

0,0 Florfenicol a,bP

XPC

CeXiofur

< 0.0001

Turkey Field Samples: 4,079 Colonies Tested McIntyre et al., 2016

0.3b Enrofloxacin

Effects of XPCTM on Salmonella Prevalence, Numbers and Antibiotic Resistance in Cloaca Swabs Commercial Layers

© Diamond V, Inc. All rights reserved. This presenta&on is the confiden&al and proprietary property of Diamond V. Diamond V does not give its consent for its distribu&on or license the use of its content.

Materials and Methods Commercial layer field trials using paired houses/farms Two Feed Treatments • CON diet: standard company diet • CON diet + XPC at either 0.75 kg/tonne or 1.25 kg/ tonne from DOC to market Birds sampled inside each commercial layer house Cloaca swabs used to sample each individual bird

Cloaca Swab Salmonella: Prevalence & Numbers

40,0

20.000,0 16.000,0

39.2a 24.6b

CFU/g

Prevalence (%)

60,0

14,551.6a

12.000,0 8.000,0

20,0

4.000,0

1,393.3b 0,0

0,0

CON a,bP

XPC

< 0.0001

Layer Field Samples; n = 3,392

CON

XPC

Antibiotic Resistance of Salmonella Recovered from Cloaca Swabs

Colonies Resistant to an Antibiotic (%)

20,0

10,0

CON

9.4a

XPC

8.9a 4.8b

4.1b

3.6a 2.3b

0,0 Florfenicol a,bP

CeXiofur

≤ 0.05

Layer Field Samples: 9,154 Colonies Tested

Enrofloxacin

NARMS Resistance Testing NARMS: National Antimicrobial Resistance Monitoring System

Established in 1996 Interagency surveillance program between FDA, USDA & CDC to track and trend changes in antimicrobial susceptibility of enteric pathogens to promote judicious use of therapies across animal agriculture and human health Data collected from 3 primary sources/sampling programs • CDC – Human Clinical Isolates • FDA – Retail Meat Samplings • USDA – Pathogen Reduction/HACCP Sampling Programs (Production)

Monitor both phenotypic (AST) and genotypic (WGS) resistance patterns of isolates • Monitoring focuses on important classes of antimicrobial therapies utilized in both veterinary and human medicine

Antibiotic Resistance of Salmonella Recovered from Ceca

Colonies Resistant to an Antibiotic (%)

100,0

98.2a

XPC

80,0

60,0

44.4b 40,0

20,0

0,0

a,bP

CON

10.8a 2.2b Cefoxi&n

≤ 0.05

Colonies Tested: 4,999

Ce\iofur

10.8a

10.5a

0.0b

0.0b

Ce\riaxone

Ce\azidime

B-­‐lactam Cephalosporins

2,4

0,0

Cefepime

Antibiotic Resistance of Salmonella Recovered from Ceca Salmonella Colonies Resistant to an Antibiotic (%)

12,0

XPC

10.9a

10.9a

8.2

8,0 5.6a

5.5a

4.4 4,0 2.2b

0,0 a,bP

CON

0.0b Ciprofloxacin

≤ 0.0261

Colonies Tested: 4,999

2.2b

0.0b Enrofloxacin

Florfenicol

Chloramphenicol

Fluoroquinolones, Phenicols and Quinolones

Nalidixic Acid

Antibiotic Resistance of Salmonella Recovered from Ceca CON

Salmonella Colonies Resistant to an Antibiotic (%)

120,0

88.7a

80,0 64.6a 60,0 40,0

53.3b

48.9b

37.8b 26.7b

20,0 0,0

a,bP

97.4a

96.9a

100,0

XPC

0,3 0,0 Gentamicin

≤ 0.0003

Colonies Tested: 4,999

Streptomycin

Aztreonam

Ampicillin

Amox-­‐cla

Aminoglycosides, B-­‐lactam Monobactam and Penicillin

Antibiotic Resistance of Salmonella Recovered from Ceca Salmonella Colonies Resistant to an Antibiotic (%)

100,0

CON

XPC

99.2a

80,0

60,0

57.8b

52.4a

57.8b 47.8a

40,0 24.4b

26.7b

20,0

0,0 a,bP

98.8a

Azithromycin

≤ 0.0039

Colonies Tested: 4,999

Sulfisoxazole

SMZ-­‐TMP

Macrolides, Sulfonamides and Tetracycline

Tetracycline

Effects of XPCTM on Avian Pathogenic E. coli prevalence & antibiotic resistance of E. coli in ceca samples commercial broilers and turkeys S. H. Miller1, E. N. Gingerich1, J. P. Carroll2, S. A. Carlson2, D. R. McIntyre1, and H. O. Pavlidis1 1. Diamond V, Cedar Rapids, IA, USA 2. Iowa State University, Ames, IA, USA © Diamond V, Inc. All rights reserved. This presenta&on is the confiden&al and proprietary property of Diamond V. Diamond V does not give its consent for its distribu&on or license the use of its content.

Materials & Methods Commercial broiler and turkey field trials using paired houses/farms Broilers: 53 d and Turkeys: 139 d Two Dietary Treatments CON diet: standard company diet CON diet + XPC at 1.25 kg/MT from DOC to market Ceca harvested from 50 birds/house after evisceration in commercial processing plants Ceca were shipped on ice overnight to Iowa State University for E. coli analysis Â

Survey of Broiler E. coli Colonies APEC Genotyping

Tested E. coli Colonies Confirmed as APEC (%)

100,0 80,0

74.7a

60,0 40,0

32.1b

20,0 0,0 CON

XPC Treatment

Broiler Field Samples

a,bP

<0.0001

6 Companies Evaluated. Total Colonies Tested: 1,046

Survey of Turkey E. coli Colonies APEC Genotyping

Tested E. coli Colonies Confirmed as APEC (%)

100,0

92.2a

80,0 60,0

43.6b 40,0 20,0 0,0 CON

XPC Treatment

Turkey Field Samples

a,bP

<0.0001

4 Companies Evaluated. Total Colonies Tested: 425

Ceca Colonies Resistant to Antibiotic (%)

Survey of Broiler E. coli Colonies: Antibiotic Resistance 100,00

CON

90.7a

80,00 68.0a 56.3a

60,00 40,00 26.9b

25.0b

15.4b

20,00 0,00 Florfenicol

a,bP

XPC

CeXiofur

< 0.0001

Broiler Field Samples Miller et al., 2017

Enrofloxacin

Ceca Colonies Resistant to Antibiotic (%)

Survey of Turkey E. coli Colonies: Antibiotic Resistance 100,00

CON

87.2a 75.3a

80,00 60,00

39.6b

40,00 26.6b

42.4a

22.3b

20,00 0,00 Florfenicol

a,bP

XPC

CeXiofur

< 0.0001

Turkey Field Samples Miller et al., 2017

Enrofloxacin

Take Home Message

Antibiotic resistance is real issue

No single solution, be critical of the interventions There is a technology that can reduce pathogensâ&#x20AC;&#x2122; antibiotic resistance

Questions Please!

If you plan for one year, plant rice If you plan for ten years, plant trees If you plan for 100 years, educate mankind â&#x20AC;&#x201C; Chinese proverb