Antibiotic Resistance

Question 1

Discuss the threat to global healthcare from antibiotic resistance, with examples

Answer 1

• over prescription of antibiotics
• acquired resistance in short time frames
• antibiotics become restricted for treatment options

Question 2

Describe the main mechanisms of antibiotic resistance

Answer 2

R+ MECHANISMS + EXAMPLES:

• VANCOMYCIN: targets D-ala, D-ala crosslink between pentapeptides in peptidoglycan structure
  R+ : acquisition of ‘D-ala, D-lac’ = continued production of peptidoglycan
• QUINOLONES: DNA gyrase ❌ inhibition
  R+ alteration of DNA gyrase [alteration of enzyme conformation
• ALTERED PORIN R+
• ACQUISITION OF NEW TARGET [NEW PBP = ❌ of β-lactams]
• TRIMETHOPRIM: targets THFA/DHFA precursor production
  R+ = overproduction of target = trimethoprim is ineffective [enzyme : substrate ratio] ❌ inhibition of competitive inhibition = continued folic acid metabolism
• alteration of target [RIFAMPICIN R+]

Question 3

Explain the different mechanisms for penicillin resistance

Answer 3

• drug inactivation via acquisition of enzyme [β-lactam R+]
• impermeability from modified cell wall/membrane
• increased efflux via ⬆️ porins = flush out antibiotic [ gram negative]
• change PBP [gram + ]
• metabolic bypass [peptidoglycan / folic acid]
• alteration of target [RIFAMPICIN R+]

Question 4

Differentiate acquired from intrinsic antibiotic resistance

Answer 4

• ACQUIRED: only develops in certain subpopulations / strains [via genetic mechanisms]
• INTRINSIC: widespread across acquired immunity through mutations in bacteria populations
• increase antibiotic tolerance
• natural barriers which ⬇️ effect (single base mutation in porin)

Question 5

Describe the role of mutation and horizontal gene transfer in the generation of antibiotic resistance

Answer 5

GENETIC MECHANISMS:
- chromosomal mediation: spontaneous mutation acquisition
MUTANTS ARE SELECTED NOT INDUCED

• exchange genetic information [plasmid transfer / common in gram ➖]
  = acquisition of plasmid = R+
• TRANSFORMATION: adopting and incorporating surrounding DNA
• TRANSDUCTION: phage infects and injects own and acquired gene into recipient bacteria
• CONJUGATION: plasmid conjugal plasmid tubes which allow genetic exchange between donor and recipient

Question 6

Describe the microbiological methods for testing antibiotic susceptibility

Answer 6

• disc diffusion test
• rings of inhibition

Question 7

Be able to give specific examples of antibiotics, their targets, and the basis of resistance for that antibiotic.

Answer 7

β-lactams: bind to PBP and block peptidoglycan production & ⬆️ autolytic response
R+: acquisition of β-lactamase enzyme = breakdown of β-lactams = R+

methicillin resistant- staphylococcus aureus = MRSA [R+ to modified β-lactams]

Question 8

Discuss the role of antibiotic stewardship in the control and prevention of antibiotic resistance.

Answer 8

• control administration
  [reducing in animal feed / stricter prescription]
• drug modification
• combination therapy
• infection control : herd immunity/ vaccination
• re-establish susceptible flora?