Antibiotic Efficacy + Resistance + Stewardship

How is efficacy demonstrated in food animals?

Against negative controls in naturally occurring disease (primarily in food animals)

How is efficacy demonstrated in humans or dogs and cats and horses?

Non-inferiority studies against approved antimicrobials

What is generic approval of an antimicrobial?

Matches a generic drug to the substantial evidence of efficacy for an approved drug

What are the 3 ways efficacy can be demonstrated?

Against negative controls in naturally occurring disease

Non-inferiority studies

Generic approval

What is the clinical success rate based on?

ARR (Attributable reduction in risk)

NNT (number needed to treat)

What is ARR?

Attributable reduction in risk

What is NNT?

Number needed to treat

What is an NNT of 1 mean?

Every animal you treat you make a difference

What can cause the NNT to be high?

Low effect of the drug

High spontaneous cure rate

Combination of both

What is the difference attributable to therapy?

You take the percentage of cases that are successful with the therapy and subtract the percentage of cases that resolve on their own

Treatment for control of respiratory disease BLANKS and BLANKS morbidity, it does BLANK prevent morbidity

SUPPRESSES and DELAYS morbidity , it does NOT prevent morbidity

T/F increasing production level increases physiological stress which increases the susceptibility to pathogens?

True

How do you calculate the NNT?

100% divided by the attributable reduction in risk

What typically happens to the NNT if you wait to evaluate success?

It increases because it gives more time for spontaneous recoveries

Why are NNTs so high when it is based on mortality?

Mortality is an infrequent outcome. This is the same concept as spontaneous recoveries

What is resistance?

A product of the interaction of the antimicrobial and a population of bacteria

What does resistance usually mean?

It means we don’t get an effective antimicrobial until later in the disease process. NOT that we do not have an antimicrobial option

What are the types of antimicrobial resistance?

Intrinsic

Acquired

What is intrinsic resistance?

Cellular mechanism for susceptibility are absent from the microbe

T/F pen G being ineffective against mycoplasma is intrinsic resistance?

True

What are the mechanism of acquired resistance?

Enzymatic inactivation
Impermeability of cell wall/membrane
Alteration in target receptors
Development of metabolic component with low binding affinity to an antimicrobial
Efflux pumps

How can resistance genes be transferred?

Singularly or in groups

How can resistance genes be transmitted singularly?

Vertical transformation to daughter cells

How can resistance be transferred in groups?

Horizontal transfer

• Transformation

• Bacteriophage transmission

• Conjugation with plasmids

What is transformation to acquire a resistant gene?

Uptake of naked DNA in environment

What pathogens had a single step mutation to high resistance against FQs?

Campylobacter jejuni, Staph. aureus, and Pseudomonas

How do most pathogens become resistant to FQs?

An initial mutation of low level resistance

A second step leading to high levels of resistance

What is the mutant selection window for FQs?

Range above the MIC but not 10X the MIC

How can we avoid being in the mutant selection windows with FQs?

A high peak with a very short T1/2 to get below MIC

What is the best way to select for resistance?

Have a very long tail as the concentration of the antibiotic falls

How many resistance genes were isolated from bacteria in the human gut in one study?

6000

How many tetracycline resistance genes have been identified?

46

How many unique beta lactamase enzymes have been identified?

2770

What does EUCAST distribution tell you?

MIC distributions for various bacterias against specific drugs

What happens to resistance as an animal is treated?

It increases with successive treatments

What are the CDC Urgent Threat Bacteria?

C. difficile
Carbapenem-resistant enterobaceriaceae
Drug-resistant Neisseria gonorrhoeae
Carbapenem-resistant Acinetobacter
Candida auris

What CDC threat level urgent microbe has been isolated in dogs?

Carbapenem-resistant Enterobacteriaceae

What are the AVMA vet med pathogens of concern with resistance for dogs and cats?

Staph pseudintermedius
Enterobacterales (all 3)
Pseudomonas aeruginosa
Enterococcus faecium

What are the AVMA vet med pathogens of concern with resistance for horses?

S. aureues
Enterobacterales (coli, proteus, enterobacter, klebsiella)
Pseudomonas aeruginosa

What are the AVMA vet med pathogens of concern with resistance for chickens?

E. coli

What are the AVMA vet med pathogens of concern with resistance for cattle?

Mannheimia haemolytica

What are the AVMA vet med pathogens of concern with resistance for swine?

E. coli
Strep. suis
Pasteurella multocida
Salmonella spp

What are the AVMA vet med pathogens of concern with resistance for sheep and goats?

S. aureus

T/F resistance is being found in plants to herbicide?

True

What is the fastest way to get resistance?

Widespread, constant or frequent pressure on a highly mutable population with a short generation time

What can we do to help prevent resistance?

Improve understanding of optimal regimens

Decrease our dependence on preventive and control uses of antimicrobials

Avoid use of antimicrobials whenever possible

What is the definition of antimicrobial stewardship?

Actions veterinarians take individually and as a profession to preserve the effectiveness and availability of antimicrobial drugs through conscientious oversight and responsible medical decision making

What are the key hurdles of antimicrobial stewardship?

Is AMR real?

Do your actions contribute?

Willing to accept risk?

T/F every time you advocate for antimicrobial stewardship, you assume a greater risk?

True

T/F you are more likely to have good stewardship early in the day, than in the afternoon?

True

What are the steps of stewardship?

1. Responsibility for appropriate diagnostics and establishment of accurate and functional case definitions

2. Is there a non-antibiotic alternative that can prevent, control, or treat this dz

3. Selection of an antibiotic which has demonstrated to be safe and effective

4. Assuring use of he antibiotic as shown to be safe and effective

5. Is the antibiotic intervention still necessary

What are the biggest struggles in antimicrobial stewardship?

Use of antimicrobial for prevention or control of disease

Using adequate case definitions to define the need to use antimicrobials

Understanding the reality of antimicrobial effects

What are are the highly important antimicrobials?

3rd and 4th gen cephalosporins

Quinolones

Polymyxins

Phosphonic acid and derivatives

What is the most common antimicrobial classes used in food animals?

Tetracyclines and ionophores

What is Goodhart’s law?

When a measure becomes a target, it ceases to be a good measure