T3-L6: Antibiotic Resistance

Question 1

What are the main causes of resistance?

Answer 1

1. Selection Pressure - gene mutations with survival advantageous mutations further the growth and propagation of the mutant strain. If the organisms finds itself in an sub-inhibitory concentration of antibiotics, the development of resistance gene will confer a survival advantage. As a result exposure to antibiotics can lead to resistance through wiping out sensitive bacteria leaving only those resistant strains..
2. Transmission of resistance organisms - Once the parent resistant organisms becomes established in the microbiome then resistance genes can be transferred between the bacteria of different species. This usually happens in the large bowel.

Question 2

How can we prevent antibiotic resistance?

Answer 2

Cause 1: Exposure to antibiotics - reduce this by antibiotic stewardship - reducing exposure to minimum safe level.

Cause 2: Transmission of resistant organisms - reduce this by minimising transmission through infection, prevention and control

Question 3

How do we identify resistance?

Answer 3

1. In vitro Testing
2. Zone of Inhibition Testing
3. Detection of antimicrobial Resistance Genes

Question 4

What is the MIC?

Answer 4

Minimum Inhibitory Concentration

Question 5

What is the relationship between the MIC and breakpoint?

Answer 5

Break point value - determined by someone else, determined by the antibiotic concentration available in the body at the site of infection. You need to look it up. If the organism MIC is lower than the break point MIC it is said to be sensitive. If the organism MIC is higher than break point MIC it than the organisms is said to be resistant.

Question 6

What methods can we use to detect antibiotic resistance genes?

Answer 6

• Nucleic amplification (mainly using PCR)
• It can be applied to any sample type e.g. MRSA testing in PBP2A testing in nose/skin samples.

The presence of a resistance gene does not always correlate with resistance as the gene needs to be switched on. The gene needs to be identified also and so it will not detect new not previously recorded resistant genes.

Question 7

Describe innate resistance mechanisms.

Answer 7

This is a fundamental property of the bacterium/antibiotic combination. It usually relates to permeability or entry of the antibiotic into the cell. For example:

- Aztreonam and colistin do not work on gram positives (all inheritance resistant)
- Aminoglycosides needs to be taken in by aerobic mechanisms and so do not work on anaerobes 
- Aminoglycosides do not work against streptococci

An example of a mechanism can include absence of target.

Question 8

Describe acquired resistance mechanisms.

Answer 8

This is an example whereby the organism has acquired a gene that encodes antibiotic resistance mechanism. Its is a new mutation or horizontal transfer. The most common acquired resistance is an antibiotic-modifying enzyme or an alteration of the antibiotic target site.

Example mechanisms include:

1. Decreased permeability
2. Enzymic degredation
3. Drug efflux
4. Target Modification

Question 9

How is resistance developed and spread?

Answer 9

Resistance genes are encoded in plasmids - circular DNA sequences transmitted within and between species mainly by conjugation. This can be by:

Horizontal transfer - Enabled by transposons and integrons - these are DNA sequences designed to be transferred from plasmid to plasmid and/or from plasmid to chromosome. Often contain cassettes with multiple resistance genes.

Vertical transfer - Chromosomal or plasmid-borne resistance genes transferred to daughter cells on bacterial cell-division.

Question 10

What are ESBL?

Answer 10

Extended-spectrum β-lactamase-producing Enterobacterales (ESBL) - enterobacterales that produce enzymes that inhibit cephalosporins and other beta lactams.

Question 11

What are CPE?

Answer 11

Carbapenemase-producing Enterobacterales (CPE)

Question 12

Give examples of pathogens resistant to antibiotics.

Answer 12

• Methicillin-resistant Staphylococcus aureus (MRSA) - resistant to fluxoacillin similar to methicillin
  
  • Vancomycin/glycopeptide-resistant enterococci (VRE/GRE)
  • Extended-spectrum β-lactamase-producing Enterobacterales (ESBL) - enterobacterales that produce enzymes that inhibit cephalosporins and other beta lactams
  • Carbapenemase-producing Enterobacterales (CPE) - inhibit carbapenemase
  • Multi-drug resistant tuberculosis (MDR-TB)
  • Extremely-drug resistant tuberculosis (XDR-TB)

Question 13

How do we monitor antibiotic resistance?

Answer 13

• Local surveillance - using alert organisms and longitudinal data to detect trends
• National surveillance
• International surveillance

Question 14

What type of bacteria are innately resistant to glycopetides such as vancomycin?

Answer 14

Glycopeptides and daptomycin do not get into gram negative bacteria