39 - ESBLs and Carbapenemases

Question 1

Importance of beta- lactams

Answer 1

• Most commonly used antimicrobial class in companion animals
• Very important in PRODUCTION medicine
• Critically important for human health
• *safe, effective, bio-available, spectrum of activity

Question 2

Beta-lactamase mechanism of action

Answer 2

• Breakdown beta-lactam ring=inactivation
• *lots of diversity
• *more of a gram NEGATIVE problem

Question 3

Beta-lactamases: “Next Big Thing” and veterinary AMR world

Answer 3

• Lack of awareness of these enzymes
• *we do NOT know much about the incidence of distribution of these resistance mechanisms in animals (companion and wildlife)

Question 4

What are some examples of beta-lactamase inhibitors?

Answer 4

• Clavulanic acid (Amox, Ticarcillin)
• Sulbactam (Amp)
• Tazobactam (limited to humans)
• *small subset of beta-lactamases
• FYI: Avibactam (humans)
  o More recently developed
  o Active against WIDER spectrum of enzymes including Class, A, C, D

Question 5

ESBL: what do we need to KNOW?

Answer 5

• They have RESISTANCE TO 3RD GENERATION CEPHALOSPORINS
• *humans and vet med

Question 6

Travel and ESBL

Answer 6

• Travel to higher prevalence regions in world IDed as a RISK factor for colonization with resistant E. coli

Question 7

Carbapenems

Answer 7

• One of LAST lines of defense
• Broad spectrum drugs

Question 8

Carbapenemases

Answer 8

• Capable of degrading vast majority of beta-lactams
• Variety of enzymes with carbapenem degrading activity
• Distinct epidemiological characteristics
• *OUR WORST NIGHTMARE

Question 9

Enzymes with carbapenem degrading activity: 3 types

Answer 9

• KPC type
• Metallo-beta-lactamases
• Oxacillinases

Question 10

New Delhi Metallo-beta-lactamase (NDM-1): epidemiology

Answer 10

• Dissemination from India and other endemic foci
• Associated with travel to Indian sub-continent (pleasure and medical tourism)
• Widely disseminated in India (water, food)
• Found in livestock in China
• *epidemiology is continuing to evolve!

Question 11

NDM-1

Answer 11

• Present on broad host range plasmids
  o Disseminated due to LATERAL spread rather than a successful clone
• *many species and genera of bacteria

Question 12

K. pneumoniae Carbapenemase (KPC)

Answer 12

• narrow host range plasmid
  o one strain of K. pneumoniae
• *have been able to track it’s movement throughout the world

Question 13

Wild bird research project

Answer 13

• *resistance was higher in URBAN birds compared to rural birds
  o Likely got it from HUMANS
• Nasty organisms all came from crows=may be a good sentinel for resistance in urban areas

Question 14

Canine UTI research project: still ongoing

Answer 14

• *very good news story: NOT finding too much resistance YET
• First line therapy’s still acceptable options

Question 15

What about imported meat-based foods?

Answer 15

• Beef, pork, poultry are heavily under surveillance
• *culinary reptiles/amphibians (food and medicinal products)
  o Half had no country-of-origin labelling
  o Found them resistant to many drugs (esp. beta-lactams)
  o *one included resistance to carbapenems: NDM-1

Question 16

What about imported plant-based foods?

Answer 16

• *plants not always cooked
• Found resistance