Antimicrobial Resistance: Veterinary and Human

Question 1

Resistance is a product of ?

Answer 1

the interaction of the antimicrobial and a population of bacteria

You can’t adequately understand what is going on without considering both

Question 2

Typer of Antimicrobial resistance:

Constitutive (intrinsic)

Answer 2

The cellular mechanisms for susceptibility are absent form the target microbe

Example: Penicillin G ineffective agianst Mycoplasma spp.

Question 3

Types of Antimicrobial Resistance:

Acquired Resistance

Answer 3

Acquisition of genetic material from other cells

• Major mechanisms of acquired resistance:
  
  • enzymatic inactivation
  • Impermeability of the cell wall memebrane
  • Alteration in target receptors
  • Development of metabolic components with low binding affinity for an antimicrobial
  • Efflux pumps

Question 4

Resistance Genes

Answer 4

• May be transferred signularly or in groups by mutiple methods:
  
  • Chromosomal mutation followed by vertical transmission to daughter cells
  • Horizontal Transfer:
    
    • transformation
    • Bacteriophage transmission
    • Conjugation using plasmids
      
      • plasmids often carry multiple antimicrobial resistance genes
      • Plasmids in turn contain transposons and integrons
      • Plasmids can often be transferred between may different bacterial genes

Question 5

Resistance isn’t just about the antimicrobial

Answer 5

• The speed of resistance mutation varies by the bacterial target for the Fluroquinolones
  
  • Campylobacter jejuni, Staph. aureus, and Pseudomonas aeruginosa as examples
    
    • these have a single step mutation to high resistance for the Fluoroquinolones
  • For other pathogens, Fluoroquinolone resistance occurs in two steps, with an initial mutation to low-lwvel resistance, with the second step leading to high-level resistiance

Question 6

Fluroquinolone Mutant Selection Window (MSW)

Answer 6

• The MSW:
  
  • based on the concept that reaching a plasma concentration greater than 10X the MIC of hte pathogen results in suppression of first-step mutants as well as susceptible Pathogens.
  • The Mutant Prevention Concentration (MPC)
  • The concentration range between 10X the MIC and the MIC is then termed the MSW. We want to stay out of that range as much as possible
  • So, hit a high peak, and then we want the shortest Half-life possible to get below the MIC
  • We only need ot do that once a day

Question 7

What is the best way ot select for resistance?

Answer 7

• Is it all about the tail
  
  • this concept comes fro the observation that no matter how carefully we strategize for maximum efficacy and minimizing selection for resistance, there is still a relatively long tail after we discontinue administration, or at the end of a single-injection “long acting” antimicrobial
• Is long and low worse than short and high?
  
  • it depends on which part of the bacterial population you are talking about
• MY best advice?
  
  • don’t use ‘em when you don’t really need ‘em
  • Get in and get out as fast as possible

Question 8

How many resistnance genes are there?

Answer 8

• More than 6.000 antibiotic resistance genes were isolated from bacteria in the human gut in ONE study.
• Forty-six tetracycline resistance genes have been identified:
  
  • 30 encode for energy-dependent efflux mechanims
  • 12 for ribosomal protection protiens
  • 3 for enzymatic degradation
  • 1 encodes for resistance in which the mechanism is unknown

Question 9

Things that are broken