What is antimicrobial resistance? Gérard MOULIN gerard.moulin@anses.fr French agency for food, environmental and occupationnal safety National agency for veterinary Medicinal Products BP 90203-35302 FOUGERES CEDEX
What is antimicrobial resistance? The ability of a microorganism to multiply or persist in the presence of an increased level of an antimicrobial agent Understanding antimicrobial resistance? Requires a good understanding of the bacterial world.
Bacteria are everywhere!!! Number of bacteria on the earth: 5 000000000000000000000000000000 Bacteria (five million trillion trillion) Microbial biomass represents half of the biomass on earth. Bacteria inside all animals combined including humans makes up less than one percent of the total amount 10 12 bacteria on skin 10 10 bacteria in mouth 10 14 bacteria in the intestine Every person coming in this room will add 37 millions bacteria in the air for each hour of stay (William Nazaro)
Bacteria can survive and develop in extreme conditions 121C, 240 bars They can adapt and resist to low or high temperatures, to acidic conditions, to high pressure, to radiations...
Antimicrobial resistance is not a new phenomenen!!! Antibioresistance is a natural adaptive phenomenon analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments identified a highly diverse collection of genes encoding resistance to β-lactam, tetracycline and glycopeptide antibiotics. Antimicrobials are chemical substances that can be produced by microorganisms that can be found in nature. Resistance can be seen as an adaptive phenomenon that bacteria have developed to survive in presence of antimicrobials produced by other microorganisms.
Adaptation capabilities One main characteristic of bacteria is its capacity to quickly adapt to various conditions: This is linked to: the ability to multiply very quickly The possibility to exchange genetic material
Bacteria can multiply very quickly When appropriate conditions are met, certain bacteria can divide every 20 minutes. It will take 10 hours for one bacteria to multiply to over one billion bacteria.
Bacteria can exchange genetic material Resistance genes can be on the chromosome or on plasmids an result from spontaneous mutation or can be acquired by : Transformation (A) Conjugation (B) Transduction (C)
Antimicrobial resistance Bacterial resistance to antimicrobial can be natural or acquired. Natural resistance: All strains from a bacterial species are resistant to an antimicrobial. It can be due to the impossibility for the antimicrobial to access to its target or due to the absence of the target. For example: Antibacterials active against bacteria cell wall will not be active against mycoplasma (absence of celll wall) Acquired resistance Transmission of genetic material from one bacteria to another (from the same species or not)
Antimicrobial mode of action et resistance Mode of action of antimicrobials Resistance mechanisms
The selection pressure: an amplification factor All antimicrobial use will lead to selection of resistant bacteria.
Co-selection Cross resistance: one resistance gene can code for resistance to different antimicrobials Co-resistance: Plasmids can carry many resistance genes coding for resistance to different antimicrobials. Therefore the use of an antimicrobial can select resistance to other antimicrobials. Example: Ban of the use of avoparcin as feed additive in 1995 in Denmark - E faecium resistance to vancomycin Resistance: Poultry: - 1995 72,7 % - 1997 20,8 % Pig: - 1995 20 % - 1997 20 % Explanation : (co-selection de VanA et de ErmB) by macrolides.
Multi-resistance
Conclusion Antibioresistance is a complex issue and no simple solution exists. Due to the drying up of the arrival of new antimicrobials on the market it is necessary to set up a sustainable management of their use. Prudent use is needed to reduce as much as possible the selection pressure of antimicrobials used in humans, animals and plants (One health concept)
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