ANTIBIOTICS AND ANTIMICROBIAL RESISTANCE: CAUSES AND POSSIBLE SOLUTIONS

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10TH EUROPEAN CONFERENCE ON PESTICIDES AND RELATED ORGANIC MICROPOLLUTANTS IN THE ENVIRONMENT & 16TH SYMPOSIUM ON CHEMISTRY AND FATE OF MODERN PESTICIDES joined to 10TH MGPR INTERNATIONAL SYMPOSIUM OF PESTICIDES IN FOOD AND THE ENVIRONMENT IN MEDITERRANEAN COUNTRIES: CONCERNS, CHALLENGES AND SOLUTIONS Bologna - Thursday - September 13th ANTIBIOTICS AND ANTIMICROBIAL RESISTANCE: CAUSES AND POSSIBLE SOLUTIONS Prof. Paolo Trevisi 1, Dr Andrea Luppi 2 1 Department of Agricultural and Food Science University of Bologna (Italy) 2 Istituto Zooprofilattico Sperimentale della Lombardia e dell Emilia Romagna (Italy)

Antimicrobial Resistance (AMR)

Source: EU AMR Action Plan 2017 Antimicrobial Resistance (AMR)

Antimicrobial Resistance (AMR) The phenotypes related with AMR are codify by specify genes

Antimicrobial Resistance (AMR) NATURAL Microorganisms naturally resistant to certain antibiotics ACQUIRED On genetic bases https://it.depositphotos.com/51938115/stock-illustration-bacteria-cell-anatomy.html

Antimicrobial Resistance (AMR) NATURAL: spontaneus genetic mutation Spontaneus genetic mutation Vertical transmission (strain dependent) It runs out in a few generations Low epidemiological importance

Antimicrobial Resistance (AMR) ACQURED: Acquisition of transmissible genetic material Transduction (batteriofages) Conjugation (transfer of genetic material) Transformation (uptake of DNA fragments) - Induced by selection pressure - Orizontal transmission (between different species) - Persistant - High epidemiological importance

AMR epidemiology Antibiotic AMR development Selection and diffusion Persistance Reduction The rate at which the prevalence of resistant strains increases has been described as a function of the level of antimicrobial exposure of bacterial populations Levy et al. (1994) introduced the threshold theory, suggesting that to trigger the occurance of resistance it is necessary to reach a certain level of a given antimicrobial drug in a particular environment. 8

Antibiotic Consumption Increasing attention on AB use in livestock: - Policy makers - Consumers - Human medicine

WHO: List of the Human Critical Importance Antimicrobials (HCIA)

9,54 7,02 mg/pcu 2.75 mg/pcu 2.90 mg/pcu 26,13 0,40 mg/pcu 29,1 mg/pcu 0,24 mg/pcu

Animal health Consumer opinion Pubblic helath 09/06/18 Piacenza, What 28 novembre impact 2015 AMR?

ANIMAL HEALTH 442 strains of E. coli F4+ Isolated from PWD pigs Tested sensitivity to 12 antibiotics

ANIMAL HEALTH Flumequina P<0.05 Enrofloxacin P<0.05 % resistant strains 100 90 80 70 60 50 40 30 20 10 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Year Luppi et al. 2015. Transbound Emerg Dis.. 62(1):67-71

ANIMAL HEALTH Tiamfenicolo P<0.05 Florfenicolo P<0.05 % resistant strains 100 90 80 70 60 50 40 30 20 10 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Year Luppi et al. 2015. Transbound Emerg Dis.. 62(1):67-71

ANIMAL HEALTH Multiresistance classes Prevalence of multi resistant strains (2002-2011) - P<0.005) Luppi et al. 2015. Transbound Emerg Dis.. 62(1):67-71 2-4 antibiotics 5-9 antibiotics >10 antibiotics 80 70 60 50 40 30 20 10 0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

PUBBLIC HELATH

It analyzes the relationship between antibiotic consumption in humans and animal populations and the frequency of resistance at European level (reference period 2013-2015).

Statistically significant association between AMC e AMR Fluorochinoloni (used in human and animals) Cefalosporine 3-4 gen. (used in human) Tetracicline e Polimixine (used in animals) (E.coli) (E.coli) (E.coli) Macrolidi (used in animals) (Campylobacter coli) Fluorochinoloni (used in animals) (Campylobacter spp. e Salmonella spp.)

Objective: Verify if the reduction of the use of antibiotic in livestock is associated with the reduction of AMR bacteria in human and animals Conclusions: Reduce the resistance The reduction of the use of antibiotic in livestock? Reduce the resistance In farm animals General population People in close contact wth the animals

There is not evidences on the magnitude of the transmission of the resistant isolates detected in human derived from the consumption of food of animal origin.

PUBBLIC HELATH Antibiotic and active metabolites AMR bacteria? Antibiotic and active metabolites AMR bacteria Possible role of the pets Adapted form: Woolhouse et al. 2015. Phil. Trans. R. Soc. B 370: 20140083.

Need of technologies for the Antimicrobial resistant genes (ARGs) elimination before the manure applications rather than waiting for subsequent attenuation in soil or Water (e.g. composted manure - Tien et al. 2017. Sci. Total Environ. 581 582:32 39). WARNING! Some ARGs have low reduction rate in the soil and water after application of manure

Maintain the therapeutic potential of the antibiotic

EUROPE COUNCIL RECOMMENDATION of 15 th November 2001 on the prudent use of antimicrobial agents in human medicine - (2002/77/EC) 12 th May 2011 The EU Parliament adopted a non-legislative resolution on the AMR (Highlight the rapid improvement of the AMR Issue) The EU Parliament ask for a communitarian strategy to counteract the AMR

EUROPE November 2011 Presented the Road map against antimicrobial resistance Road map: 7 main areas and 12 specific actions 1. Making sure antimicrobials are used appropriately in both humans and animals 2. Preventing microbial infections and their spread 3. Developing new effective antimicrobials or alternatives for treatment 4. Cooperating with international partners to contain the risks of AMR 5. Improving monitoring and surveillance in human and animal medicine 6. Promoting research and innovation 7. Improving communication, education and training

2011-2016 EC AMR Action Plan evaluation RECOMMENDATIONS AMR problem persists and continued action is needed Support and assist EU Member States as big differences still exist between them Reinforce the One Health approach (incl. environment) Pursue coordination and collaboration on research and innovation and boost the development of new antimicrobials, alternatives, vaccines and rapid diagnostic tests. Enhance EU international cooperation

New EU Action Plan against AMR Key objectives: 1. Making the EU a best practice region 2. Boosting research, development and innovation 3. Shaping the global agenda

SOLUTION Guidelines for the prudent use of antimicrobials in human and veterinary medicine Responsible use Preventive strategies AMR reduction Animal health

SOLUTION Wastewater treatment: - Oxidative processes - Membrane based process - Adsorption processes Need for removal the antibiotic at very low concentration

EDUCATION World Organisation for Animal Health (OIE) European Centre for Disease Prevention and Control

Take home message Maintain the therapeutic potential of the antibiotic in human an veterinary medicine! One Health approach Fonte: http://www.extension.org

This work is based upon work from COST Action FA1401 (PiGutNet), supported by COST (European Cooperation in Science and Technology) THANK YOU FOR YOUR ATTENTION Contact: Prof. Paolo Trevisi paolo.trevisi@unibo.it http://www.cost.eu/cost_actions/fa/fa1401 http://www.pigutnet.eu/