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