animal production: sources, prevalence and prevention Nicole Kemper - - PowerPoint PPT Presentation

MIAVIT International Seminar, 3rd September 2019

Antibiotic-resistant bacteria in modern animal production: sources, prevalence and prevention

Nicole Kemper

Veterinary Specialist in Microbiology and Animal Hygiene

Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour

Antimicrobials/Antibiotics  substances that kill or inhibit the growth of micro-

• rganisms (OIE 2016)

 antibacterial class of greatest interest for public health

Background

Bacteria  unicellular microorganisms  can be pathogenic (i.e. Clostridium perfringens)  can be zoonotic (Salmonella, Campylobacter, Escherichia coli)

Jack0m/Getty Images

Antimicrobials/Antibiotics

Background

Antibiotic resistance

X

 bacteria are non-susceptible  antibiotic substance is not efficient  bacterial infections cannot be treated anymore = ability of microorganisms to proliferate in presence of an antibiotic that generally inhibits or kills microorganisms of the same species (RUMA, 2018)

Antibiotics  to control infections  to increase feed efficiency and promote growth  presence of antibiotic residues in feed and environment

(Carvalho & Santos, 2016)

 massive use has led to antibiotic resistance (Mehdi et al. 2018)  growing global threat

Background

Urgent need to limit the use of antibiotics!

http://www.effort-against-amr.eu/

„One Health“

 antibiotic resistance affects animal and human health

Antibiotics

Background

Urgent need to limit the use of antibiotics  eliminate inappropiate uses  need for effective alternatives Keep antibiotics as useful tool in treatment

Global antimicrobial consumption in livestock

(milligrams per 10 km2 pixels) Van Boeckel et al. PNAS 2015

Background

Quantity of antibiotics in animal production in Germany

(Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, 2017)

(QS 2019)

Background

Quantity of antibiotics (in tons) in German poultry (2014 and 2018) Aminoglycosids Penicillins total Polypeptides

Selection under antibiotic presence: acquired resistance

Antibiotic resistance

(Brower, CDC)

(Wright 2010)

Antibiotic resistance

 different mechanisms of resistance  sometimes more than one: multi-resistance

Ongoing selection processes

Antibiotic resistance

(Clatworthy et al. 2007)

Antibiotic classes  Penicillins

 Cephalosporins  Carbapenems  Aminoglycosides  Tetracyclines  Fluoroquinolones  Sulfonamides  Vancomycin (reserve antibiotic) Antibiotic resistance: examples

Relevant resistant bacteria  ESBL-(Extented spectrum beta

lactamase) producing bacteria

 MRSA (Methicillin resistant

Staphylococcus aureus)

 fluorochinolone-resistant Campylobacter/Salmonella  VRE (Vancomycin-resistant Enterococci)

Resistant bacteria in poultry  e.g. 43% of isolated Salmonella enterica from Canadian poultry farms: simultaneously resistant to ampicillin, amoxicillin, clavulanic acid, ceftiofur, cefoxitim and ceftriaxone (Diarra et al. 2014)  many reports on emerging multi-resistant bacteria in poultry

Prevalence

Prevention = Antibiotic free production How can it be realised? What should be realized?  growth promotion (EU, USA: ban of antibiotics already reality)  prevention of infections  treatment of infections

Prevention

Alternatives to antibiotics

Aims of alternative strategies  Enable … animal health and low mortality rates … high performance (e.g. growth rate) … consumer health … environmental protection

Alternatives to antibiotics

Feeding strategies Health manage- ment Farm manage- ment

Holistic approach = combination of various approaches to realise antibiotic free production  husbandry and management  vaccination  feed additives  alternative treatment

Alternatives to antibiotics

Husbandry and management  24/7: man-made environment  good concept of farm hygiene  high biosecurity

Alternatives to antibiotics

Husbandry and management  enable high animal health and welfare  consider all potential influencing factors: ventilation, pest control, water hygiene and biofilms, food hygiene, litter… The outcome of all further applied measures is highly variable between farms and strongly related to general husbandry conditions

Alternatives to antibiotics

Vaccination  administration well before infection  strategic approach  some diseases regulated by law  consultancy by veterinarian  ensure correct application: correct age of the animals, health status, correct dosage and administration mode, hygienic application

Alternatives to antibiotics

Feed additives as non-therapeutic alternatives

• 1. Phytogenics
• 2. Probiotics
• 3. Prebiotics
• 4. Organic acids
• 5. Others

 national regulations/market approvals differ

Alternatives to antibiotics

(Gadde et al. 2017)

Alternatives to antibiotics

(Alagawany et al. 2018)

Mechanisms often not fully understood!

• 1. Phytogenics/Phytochemicals

 natural bioactive compounds derived from plants, used in animal feed to enhance productivity (Windisch et al., 2008)  secondary metabolites: terpenoids, phenolics, alkaloids, glykosides (Huyghebaert et al. 2010)

Alternatives to antibiotics

• W. Dedl

• 1. Phytogenics/Phytochemicals

 antimicrobial: ginger, pepper, cumin, coriander, oregano, rosemary, sage, thyme, mustard, cinnamon, garlic  positive effects for different substances shown in several studies (Pew Charitable Trust 2017)  efficacy depends on substance and part of the plant

(EMA/EFSA 2017)

Alternatives to antibiotics

Phytogenics: beneficial effects

(Yadav et al. 2016)

• 2. Probiotics

 mono or mixed cultures of live organisms which confer a health benefit to the host (WHO/FAO 2001)  defined or undefined  Bacillus, Bifidobacterium, Enterococcus, Lactobacillus, Streptococcus, Lactococcus spp., yeast (Saccharomyces spp.)  establish favourable microenvironment in the gut: beneficial bacteria, pathogenic bacteria

Alternatives to antibiotics

(Simon et al. 2001; Patterson&Burkholder 2003; Griggs&Jacob 2005; Kabir 2009)

Istockphoto.com

• 2. Probiotics

 creating a hostile environment for harmful bacterial species (through production of lactic acid, SCFA, and reduction in pH)  competing for nutrients with undesired bacteria  production/secretion of antibacterial substances (e.g. bacteriocins by Lactobacillus, Bacillus spp.)  inhibition of bacterial adherence and translocation

Alternatives to antibiotics

(Gadde et al. 2017)

• 2. Probiotics

 single/multiple strains: broiler performance  + immune function  + intestine development   beneficial effects also in layers and turkeys  inconsistent findings due to different formulations and experimental settings

Alternatives to antibiotics

(Gadde et al. 2017)

• 2. Probiotics: Competitive exclusion

 undefined probiotics  derived from adult animals  given soon after hatching  help to establish a community of beneficial bacteria before pathogens can colonize them  shown to be very effective

Alternatives to antibiotics

(Methner et al. 2019)

Gogineni et al. 2013

• 2. Probiotics

The ideal probiotic:  should withstand processing and storage  survival in the gastric acidic environment  adhere to epithelium or mucus in the intestines  produce antimicrobial compounds  modulate immune responses  without any side effects (live cultures!)

Alternatives to antibiotics

(Edens 2003; Patterson&Burkholder 2003; Cheng et al. 2014)

fotolia

• 3. Prebiotics

 indigestible feed compounds with health benefit on the host associated with modulation of the microbiota (FAO, 2007)  altering the intestinal microbiota: selective enrichment of beneficial microorganisms associated with health and well- being (Simmering&Blaut 2001; Samantha et al., 2013)  non-starch polysaccharides, oligosaccharides: e.g. mannan

• ligosaccharide, fructooligosaccharide, inulin, oligofructose,

lactulose (Patterson&Burkholder 2003; Steiner 2006)

Alternatives to antibiotics

iStock

• 3. Prebiotics

 prevent pathogen colonization either by binding directly or by competitive exclusion  promote growth of beneficial microbes  stimulate them to produce bacteriocins and lactic acid

Alternatives to antibiotics

(Spring et al. 2000)

• 3. Prebiotics

 numerous trials with prebiotic supplementation in broilers: growth and performance(Gadde et al. 2017)  inconsistent efficacy Synbiotics  probiotic + prebiotic  different outcomes of studies  no additional effects (Vahjen et al. 2019)

Alternatives to antibiotics

• 4. Organic acids

 formic, acetic, propionic, butyric, lactic, malic, tartaric, citric acids  various studies showed positive effects on feed convertion and growth rate in poultry (Gadde et al. 2017)  beneficial effects enhanced with blends: feed conversion rate in broilers  (Samanta et al. 2008, 2010)

Alternatives to antibiotics

VectorStock

• 4. Organic acids

Possible effects  reducing pH level of the upper gastrointestinal tract  altering the gut microflora  increasing nutrient digestibility by elevating protein and dry matter retention, mineral absorption, phosphorous utilization  direct effects on epithelial cells: gut health

Alternatives to antibiotics

(Gadde et al. 2017)

• 5. Others

Clay  efficacy data lacking Copper, zinc and other heavy metals  can promote growth  concerns about residues and increased rates of resistance against certain antibiotics

Alternatives to antibiotics

(Pew Charitable Trust 2017)

Therapeutic alternatives

• 1. Bacteriophages
• 2. Antimicrobial peptides
• 3. Hyperimmune egg yold

antibodies and immun- modulators

• 4. Enzymes

Alternatives to antibiotics

(Gadde et al. 2017)

• 1. Bacteriophages

 = viruses that infect and kill bacteria (bacteriolysis)  often very specific: targeted approach  bacteria can become resistance  extremely time-sensitive administration

Alternatives to antibiotics

Shutterstock

• 1. Bacteriophages

Bacteriolysis

Alternatives to antibiotics

(Roach&Debarbieux 2017)

• 1. Bacteriophages

 over 870 described species (Wernicki et al. 2017)  used in experimental studies as single bacteriophages or cocktails  studies in chicken showed successful treatment of E. coli, Salmonella enterititis and Clostridium infections

(Huff et al. 2004, Fiorentin et al. 2005, Wernicki et al. 2017)

Alternatives to antibiotics

• 2. Antimicrobial peptides

 short molecules with antibacterial properties  sometimes produced by probiotics  effective in growth and gut health promotion (EMA/EFSA 2017)

Alternatives to antibiotics

(Zhang&Gallo 2017)

• 3. Hyperimmune egg yold antibodies and other immune

modulators  egg yold antibodies  cytokines, lipopolysaccharides, bacterial DNA segments  limited research with promising results

Alternatives to antibiotics

Viv.net

• 4. Enzymes

 Hydrolases: endolysines (virolysines) and lysozymes  degrade peptidoglycanes in bacterial cell walls  different sources: bacteriophages, bacteria, plants, animals  promising, but studies are still lacking

Alternatives to antibiotics

(Pew Charitable Trust 2017)

Alternatives to antibiotics in Poultry

Alternatives to antibiotics in Poultry

(Pew Charitable Trust 2017)

Antibiotics should be kept as effective tool: Prudent use of antibiotics If possible:  testing for susceptibility to find effective antibiotic  use of narrow spectrum antibiotics  concentration high enough  duration of treatment long enough

Administration of antibiotics

WHO

Conclusion

Interaction between several approaches  combining different means  optimising housing and herd management  farm-specific strategies  alternative products: efficacy and cost-effectiveness are key  sharing experiences and knowledge

Thanks for your attention!