MIAVIT International Seminar, 3 rd 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
Background Antimicrobials/Antibiotics substances that kill or inhibit the growth of micro- organisms (OIE 2016) antibacterial class of greatest interest for public health Bacteria unicellular microorganisms Jack0m/Getty Images can be pathogenic (i.e. Clostridium perfringens ) can be zoonotic ( Salmonella , Campylobacter, Escherichia coli )
Background Antimicrobials/Antibiotics X Antibiotic resistance bacteria are non-susceptible = ability of microorganisms to proliferate in presence of an antibiotic substance is not efficient antibiotic that generally inhibits or kills microorganisms of the same species (RUMA, 2018) bacterial infections cannot be treated anymore
Background 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 Urgent need to limit the use of antibiotics!
„ One Health “ antibiotic resistance affects animal and human health http://www.effort-against-amr.eu/
Background Antibiotics Urgent need to limit the use of antibiotics eliminate inappropiate uses need for effective alternatives Keep antibiotics as useful tool in treatment
Background Global antimicrobial consumption in livestock (milligrams per 10 km2 pixels) Van Boeckel et al. PNAS 2015
Quantity of antibiotics in animal production in Germany (Bundesamt für Verbraucherschutz und Lebensmittelsicherheit, 2017)
Background Quantity of antibiotics (in tons) in German poultry (2014 and 2018) Aminoglycosids Penicillins Polypeptides total (QS 2019)
Antibiotic resistance Selection under antibiotic presence: acquired resistance (Brower, CDC)
Antibiotic resistance different mechanisms of resistance sometimes more than one: multi-resistance (Wright 2010)
Antibiotic resistance Ongoing selection processes (Clatworthy et al. 2007)
Antibiotic resistance: examples Antibiotic classes Relevant resistant bacteria ESBL- (Extented spectrum beta P enicillins Cephalosporins lactamase) producing bacteria MRSA (Methicillin resistant Carbapenems Staphylococcus aureus) Aminoglycosides fluorochinolone-resistant Tetracyclines Campylobacter / Salmonella Fluoroquinolones VRE (Vancomycin-resistant Sulfonamides Enterococci ) Vancomycin (reserve antibiotic)
Prevalence 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
Prevention 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 Alternatives to antibiotics
Alternatives to antibiotics Aims of alternative strategies Enable … animal health and low mortality rates … high performance (e.g. growth rate) … consumer health … environmental protection Farm Health Feeding manage- manage- strategies ment ment
Alternatives to antibiotics 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 (Gadde et al. 2017)
Alternatives to antibiotics Mechanisms often not fully understood! (Alagawany et al. 2018)
Alternatives to antibiotics 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) W. Dedl
Alternatives to antibiotics 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)
Phytogenics: beneficial effects (Yadav et al. 2016)
Alternatives to antibiotics 2. Probiotics mono or mixed cultures of live organisms which confer a health benefit to the host (WHO/FAO 2001) Istockphoto.com defined or undefined Bacillus , Bifidobacterium , Enterococcus , Lactobacillus , Streptococcus , Lactococcus spp., yeast ( Saccharomyces spp.) establish favourable microenvironment in the gut: beneficial bacteria , pathogenic bacteria (Simon et al. 2001; Patterson&Burkholder 2003; Griggs&Jacob 2005; Kabir 2009)
Alternatives to antibiotics 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 (Gadde et al. 2017)
Alternatives to antibiotics 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 (Gadde et al. 2017)
Alternatives to antibiotics 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 Gogineni et al. 2013 (Methner et al. 2019)
Alternatives to antibiotics 2. Probiotics The ideal probiotic: fotolia 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!) (Edens 2003; Patterson&Burkholder 2003; Cheng et al. 2014)
Alternatives to antibiotics 3. Prebiotics iStock 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 oligosaccharide, fructooligosaccharide, inulin, oligofructose, lactulose (Patterson&Burkholder 2003; Steiner 2006)
Alternatives to antibiotics 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 (Spring et al. 2000)
Alternatives to antibiotics 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) VectorStock
Alternatives to antibiotics 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 (Gadde et al. 2017)
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