25/26. Antimicrobial resistance

Explain the relationship between antimicrobial and antibiotics

Antimicrobials: agents that kill/inhibit growth of microorganisms, including bacteria, viruses, fungi and protozoa

Antibiotics: subset of antimicrobials that target bacteria

Distinguish between intrinsic and acquired resistance

Intrinsic(innate): natural ability of bacteria to resist certain antibiotics without previous exposure/mutation - due to inherent structure/functional traits

(many bacteria naturally reists antimicrobials produced by fungi and other microbes)

Acquired resistance: arises from random mutations or horizontal gene transfer

(antibiotic use favors resistant bacteria)

Describe random (spontaneous) mutation

Resistant mutants arise randomly (errors in DNA replication) before antibiotic exposure, so occasionally one culture holds a 'jackpot' of resistant cells

Describe horizontal gene transfer

Once a single bacterium mutates to become resistant to antibiotics, it can transfer that resistance gene to other bacteria through horizontal gene transfer (Conjugation - transfer plasmids)

These genes can be rapidly shared between bacteria, even across species

What are the major mechanisms of resistance

1. efflux

2. inactivating enzyme

3. change target

4. immunity and bypass

5. Reduced permeability

Describe cross resistance

One resistance mechanism protects against multiple drugs (often in same class)

- often due to similar target sites or shared resistance mechanisms

Simplify: the landlord changes one lock, and every similar key stops working

Describe co-resistance

Multiple different resistance genes co-exist = resistance against multiple drugs

- often carrier on the same plasmid or mobile element

Simplify: think of the plasmid as the key ring and the resistance genes as the keys. You get all the keys even if you only needed one

Describe co-selection

The consequence of co-resistance under antibiotic pressure (selection)

- one antibiotic use = selects bacteria carrying resistance gene linked to that antibiotic and other resistance genes

Differentiate "urgent" vs "serious" threats as defined by the CDC

Urgent: immediate danger, few or no treatment options, needs aggressive action

Serious: significant threat, some treatments remain, needs sustained monitoring and prevention

Discuss critically important antimicrobial classes for human and animal medicine as defined by WHO

Purpose: Rank antimicrobials by importance for human medicine

Discuss critically important antimicrobial classes for human and animal medicine as defined by WOAH

Covers antimicrobials used in food-producing animals; excluding drugs used only in human medicine or only as growth promoters

What are microbes are the threats linked to animal agriculture? (include their CDC distinction)

Carbapenem-resistant Enterbacterales (CRE) - URGENT

ESBL producing Enterbacterales - SERIOUS

Campylobacter - SERIOUS

Nontyphoidal Salmonella - SERIOUS

Vancomycin resistant Entercoccus (VRE)- SERIOUS

Methicillin resistant Staphylococcus aureus (MRSA) - SERIOUS

Carbapenem-resistant Enterbacterales (CRE)

- antibiotic class

- WHO rank

- WOAH rank

- animal link

- carbapenems

- WHO: Humans only

- WOAH: not listed

- NOT approved FA, but found on farms

ESBL producing Enterbacterales

- antibiotic class

- WHO rank

- WOAH rank

- animal link

- 3rd/4th gen cephalosporins

- WHO: HPCIA

- WOAH: VCIA

- Cattle & poultry (ceftiofur use)

Campylobacter

- antibiotic class

- WHO rank

- WOAH rank

- animal link

Fluoroquinolones & Macrolides

- WHO: HPCIA/ CIA

- WOAH: VCIA

- poultry & cattle; fluoroquinolone and macrolide resistance

Nontyphoidal Salmonella

- antibiotic class

- WHO rank

- WOAH rank

- animal link

- Macrolides

- WHO: CIA

- WOAH: VCIA

- beef, poultry, pork (ceftriaxone & azithromycin resistance)

Vancomycin resistant Entercoccus (VRE)

- antibiotic class

- WHO rank

- WOAH rank

- animal link

- glycopeptides

- WHO: humans only

- WOAH: not listed

- avoparcin growth promoter in the EU

Methicillin resistant Staphylococcus aureus (MRSA)

- antibiotic class

- WHO rank

- WOAH rank

- animal link

- Anti- staph penicillins

- WHO: HIA

- WOAH: VCIA

- livestock associated MRSA in pigs

Describe major emerging resistance challenges with ESBLs

ESBLs = Extended spectrum B-lactamases

- found worldwide in food animals and retail meat

Describe major emerging resistance challenges with carbapenem resistance (CRE)

- gut bacteria can pick up and share carbapenemase genes on plasmids

- rare in agriculture, but plasmids can spread

- carbapenems are not approved for US food animals, but used extra label on dogs and cats

- CRE genes have been found on US farms

Describe major emerging resistance challenges with fluoroquinolones

- before resistance was mostly random mutations

- there are plasmid borne resistant genes now to help them live long enough to gain mutations

Describe major emerging resistance challenges with macrolide and colistin resistance

- macrolides widely used in US cattle

- cross resistance to azithromycin (key human drug)

- colistin is an old never marketed drug in US, resistance has been found worldwide

Describe major emerging resistance challenges with vancomycin and methicillin resistance (VRE, MRSA)

VRE: emerged from hospitals, not farms (opposite of EU)

MRSA: began in humans as susceptible, went to pigs and became resistant, and now pigs can give it back - found in US

Summarize GFI 209: Judicious use of medically important antimicrobials

- you decide when a medically important antimicrobial is justified (producers cant use them without you)

- prevention needs a reason: a specific disease risk on that operation, NOT routine use

- growth or feed efficiency is NEVER a valid reason for these drugs

Summarize GFI 213: Feed and water

Feed and water uses moved to vetinary oversight

- You write the VFD: requires a valid VCPR

- You set the details (species, indication, dose, duration, # of animals)

- Records: VFD copies must be kept for 2 years, by you, the producer and the feed distributor

Summarize GFI 263: All remaining OTC medically important antimicrobials

- No more feed store antibiotics: must get them from you with your prescription

- every prescription requires a valid VCPR

- you're now the gatekeeper for any livestock owner who you may have never met

(Still OTC: dewormers, vitamins, probiotics, and non medically important products)

Summarize GFI 273: defined duration use

- your VFDs will have a clear stop date (no more feed continiously orders anymore)

- shorter defined courses mean less selection pressure, with the same animal health goal

Discuss the roles and responsibilities of veterinarians in antimicrobial stewardship

1. Commit to stewardship (maintain VCPR)

2. Prevent disease first

3. Select and use antimicrobial judiciously

4. evaluate your use

5. educate and stay current

Describe non-antibiotic alternatives

1. Prevention first (vaccines; biosecurity)

2. Bacteriophages

3. Replace the population (probiotics; microbial transplants)

4. essential oils (natural antimicrobial compounds)