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Alternatives to Antibiotics Competitive Exclusion Dik Mevius, IPPE February 2013
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Alternatives to Antibiotics Competitive Exclusion

Mar 25, 2016

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Dr. Dik Mevius, professor of antimicrobial resistance at the University of Utrecht in the Netherlands, presenta at the Antibiotics Conference during the International Poultry Expo.
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Page 1: Alternatives to Antibiotics Competitive Exclusion

Alternatives to Antibiotics Competitive Exclusion

Dik Mevius, IPPE February 2013

Page 2: Alternatives to Antibiotics Competitive Exclusion

Principle of CE (Wikipedia)

n  In ecology, the competitive exclusion principle, is a proposition which states that two species competing for the same resources cannot coexist if other ecological factors are constant. One of the two competitors will always overcome the other, leading to either the extinction of this competitor or an evolutionary or behavioural shift towards a different ecological niche. The principle has been paraphrased into the maxim "complete competitors cannot coexist".

n  First described by Grinnell, J. (1904). "The Origin and Distribution of the Chest-Nut-Backed Chickadee". The Auk (American Ornithologists' Union) 21 (3): 364–3821.

n  Gause, G.F. (1934). The struggle for existence. Baltimore, MD: Williams & Wilkins n  Hardin, G. (1960). The Competitive Exclusion Principle. Science 131, 1292-1297.

Page 3: Alternatives to Antibiotics Competitive Exclusion

www.southtexascollege.edu

Page 4: Alternatives to Antibiotics Competitive Exclusion

http://www.nature.com/scitable/knowledge/library/the-maintenance-of-species-diversity-13240565

Page 5: Alternatives to Antibiotics Competitive Exclusion

History of CE in poultry

n  First used in poultry in 1971 to control a S. Infantis outbreak in Finland l  Rantala and Nurmi, Br.

Poult. Sci., 14: 627-630. 1973

Page 6: Alternatives to Antibiotics Competitive Exclusion

Mechanisms involved (Nurmi et al, 1992)

n  (1) Competition for limiting nutrients; n  (2) Competition for attachment sites on the mucosa; and n  (3) Production of antibacterial substances, e.g. volatile

fatty acids, bacteriocins.

Page 7: Alternatives to Antibiotics Competitive Exclusion

Purpose of usage of CE in poultry

n  Predominantly l  Control of colonization of enteropathogens

•  Salmonella, –  Campylobacter –  Pathogenic multi drug resistant E. coli –  Clostridium infection –  ESBL-producing E. coli

Page 8: Alternatives to Antibiotics Competitive Exclusion

Types of CE-flora

n  Freeze or vacuum dried intestinal flora of adult SPF animals l  Commercialized l  Home made

1988, Veterinary Quarterly, 10:4,249-255

Page 9: Alternatives to Antibiotics Competitive Exclusion

CE used in Salmonella control in 1980/1990s in The Netherlands

Broilers

n  Spray of chickens/eggs in hatching units

Reproduction animals

n  Spray of adult animals after 10 days orally administered enrofloxacin “Salmonella repair”

Page 10: Alternatives to Antibiotics Competitive Exclusion

NUTRITIONAL EFFECTS OF BROILACT® IN POULTRY PRODUCTION 429TABLE 2. Effects of the BROILACT® treatments on pH and volatile fatty acid concentrations (VFA)

in the intestines of the broiler chickens at 12 d of age

a,bMeans within a row with no common superscript differ significantly (P < 0.05).*P < 0.05.**P < 0.01.

BROILACT® BROILACT®Variable Control 1 × 5 × SEM Significance

pH duodenum 6.02 5.97 5.97 0.011 NSpH ileum 7.45 7.75 7.56 0.066 NSpH ceca 5.24 5.32 5.63 0.081 NSIleum, mmol/gAcetic acid 46.60 55.00 31.60 4.000 NS (P = 0.054)Propionic 0.36 0.45 0.43 0.018 NS (P = 0.075)Butyric 0.20a 0.06ab tracesb 0.033 *Isovaleric 0.22 0.17 0.15 0.013 NS (P = 0.08)Capronic 0.03b 0.15a 0.15a 0.021 **Ceca, mmol/gAcetic acid 109.90 109.90 118.20 3.830 NSPropionic 6.80b 16.20ab 17.50a 1.890 *Isobutyric 0.31 0.51 0.62 0.057 NS (P = 0.055)Butyric 14.80 13.60 18.20 1.130 NSIsovaleric 0.29b 0.59ab 0.69a 0.059 *Valeric 0.59b 1.27ab 1.57a 0.166 *

TABLE 3. Effects of the BROILACT® treatments on pH, volatile fatty acids (VFA) and lactic acidconcentrations in the intestines of the broiler chickens at 31 d of age

a,bMeans within a row with no common superscript differ significantly (P < 0.05).*P < 0.05.**P < 0.01.***P < 0.001.

BROILACT® BROILACT®Variable Control 1 × 5 × SEM Significance

pH duodenum 5.94 5.95 6.05 0.024 NSpH ileum 7.45 7.63 7.76 0.061 NSpH ceca 5.99 5.89 5.94 0.052 NSIleum, mmol/gAcetic acid 46.60 51.60 53.30 1.000 NSPropionic traces traces traces . . . . . .Butyric traces traces traces . . . . . .Lactic 18.90 5.60 8.90 3.330 NSCeca, mmol/gAcetic acid 146.50 133.20 131.60 2.830 *Propionic 8.10b 21.60a 22.90a 1.750 ***Isobutyric 0.83 0.99 0.91 0.047 NSButyric 26.10 21.60 20.40 1.020 NS (P = 0.09)Isovaleric 0.98 0.98 0.78 0.137 NSValeric 1.80 2.50 2.60 0.140 NS (P = 0.051)Capronic 0.20 0.03 0.04 0.050 NSLactic 2.00a 1.40b 1.30b 0.100 **

environment take place, the number of C. perfringensmay increase, which, in turn, results in a greaterproduction of alpha-toxin by C. perfringens, and out-break of necrotic enteritis may be induced (Fukata et al.,1991). Sakata (1987) demonstrated in rats that intralumi-nally infused VFA accelerated the crypt cell productionrate and increased the gut-wall mass. The stimulationwas most efficient with butyrate. The positive effect ofdietary antibacterials appears to be related to theelimination of fermentative microorganisms, mainly

butyric acid producers (especially clostridia), from thesmall intestine (Choct et al., 1996). This effect has beenshown to decrease the gut-wall mass and stimulatenutrient absorption (Parker and Armstrong, 1987; Visek,1978), and supports the improved nutrient digestibilityfound in the present study.BROILACT® increased slightly the production of

propionic acid and clearly that of capronic acid (P <0.01) in the ileum at 12 d of age. The cecal samples takenat the same age showed an increase in the concentrationof propionic (P < 0.05), isovaleric, and valeric acids.

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Multi drug resistant E. coli

Avian Dis. 2002 Jan-Mar;46(1):198-202. Effect of a commercial competitive exclusion culture on reduction of colonization of an antibiotic-resistant pathogenic Escherichia coli in day-old broiler chickens. Hofacre CL, Johnson AC, Kelly BJ, Froyman R. Department of Avian Medicine, College of Veterinary Medicine, University of Georgia, Athens 30602-4875, USA.

n  CE-flora applied to day-old-chickens resulted in 3 – 4 log10 reductions of E. coli O78:K80 colonization of the GI tract

Page 12: Alternatives to Antibiotics Competitive Exclusion

Avian Dis. 2001 Jan-Mar;45(1):149-56. Reduced incidence of Clostridium perfringens-associated lesions and improved performance in broiler chickens treated with normal intestinal bacteria from adult fowl. Kaldhusdal M, Schneitz C, Hofshagen M, Skjerve E. National Veterinary Institute, Dep, Oslo, Norway. Broilact in combination with Narasin resulted in a non-significant effect in a field trial on a farms

Page 13: Alternatives to Antibiotics Competitive Exclusion

Effect of CE on ESBLs?

Will CE flora prevent transfer of epidemic ESBL-carrying plasmids?? Is the reduction sufficient to control risks attributed to poultry??

Prerequisite: CE-flora should contain E. coli with the same plasmids on which the ESBLs are located (IncI1)

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ESBL increase in young boilers (first week 0 – 100%)

n  Associated by usage of ionophores?? l  “CE-effect” on Gram-

Positive flora??

Transmission in the Poultry production pyramid

GPS

PS

Broilers

AmpC

ESBL + AmpC

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Summarize the effect of CE-flora

n  Not an alternative to antibiotics n  Supports the control of enteropathogens/resistant

organisms l  In the absence of antibiotics!! l  No evidence that it results in control of bacterial infections

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How can the ‘health’ of the animals be controlled without systematic usage of antibiotics??

n  The solution is not in a bottle!! n  Needs a holistic approach!! n  Not based on substances with antimicrobial activity!!

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Pathogen    

Animal    

Environment  

Sustainable, Healthy Food-Animal Production

Gut  Health   High  Health  

Page 18: Alternatives to Antibiotics Competitive Exclusion

Pathogen  Virulence  Preven4on  (vaccine)  Diagnos4cs  Epidemiology    

Animal  Microbiome  Immunity  Physiology  Epigene4cs  Metabolism          

Environment  Feed  quality  Supplements  An4bio4cs  Management  Zoonotechnics      

Sustainable, Healthy Food-Animal Production

Gut  Health  

How can gut health be measured How can we control it

Page 19: Alternatives to Antibiotics Competitive Exclusion

As an alternative to antibiotics

n  To balance “gut health” without antibiotics??

l  CE-flora could play a crucial role in the interaction between environmental and host related factors.

Page 20: Alternatives to Antibiotics Competitive Exclusion

However

n  CE-flora and antibiotics are incompatible l  In feed, drinking water administration of antibiotic AB for

therapy or as growth promoter will result –  in high concentrations in the GI-tract

–  Residues in litter and drinking water

Page 21: Alternatives to Antibiotics Competitive Exclusion

Residues in drinking water

n  On 49% of Dutch Broiler farms (N = 87) antibiotic residues were found in drinking water while no antibiotics were administered

Page 22: Alternatives to Antibiotics Competitive Exclusion

Residues found in 87 broiler farms

1 – 1000 PPB

Page 23: Alternatives to Antibiotics Competitive Exclusion

Conclusions

n  CE-flora l  not an alternative to antibiotics l  It may support ‘gut health’ in the absence of antibiotics