Lecture Notes: Mechanisms of Bacterial Resistance

Overview

• Resistance in bacteria is a major issue.
• Historical comparison (1991 vs. 2021) shows increased resistance, evidenced by fewer antibiotics being effective over time.

Mechanisms of Resistance

• Genetic Diversity and Resistance:

  • Bacteria acquire resistance genes through transformation and conjugation, spreading resistance quickly.

• Cell Wall Alterations:

  • Some bacteria can survive without a cell wall (L-form), rendering cell wall-targeting antibiotics ineffective.
  • Example: Tuberculosis hides in tissues such as the lungs.

• Alteration of Targets:

  • Mutations can change bacterial proteins, preventing antibiotics from binding effectively.
  • Rapid reproduction increases mutation rate.

• Alteration of Membrane Permeability:

  • Bacteria may change membrane proteins, preventing antibiotic penetration.

• Enzyme Development:

  • Beta Lactamase: An enzyme that breaks down the beta-lactam ring in antibiotics, rendering them ineffective.
  • Alteration of Enzymes: Bacterial enzymes may still function in the presence of inhibitors, continuing metabolism.

• Alteration of Metabolic Pathways:

  • Bacteria may bypass metabolic steps targeted by antibiotics, continuing essential processes.

Antibiotic Prescription and Resistance

• First-line Drugs: Initial antibiotics prescribed should ideally work against the infection.
• Second-line Drugs: Used if the first-line drug fails due to developed resistance.
• Cross-resistance: Avoid prescribing similar mechanism drugs if the first fails.

Strategies to Limit Drug Resistance

• Proper Dosage and Duration:

  • Prescribe high enough doses for long enough periods to kill all pathogens and mutants.
  • Use synergistic antibiotic combinations (e.g., penicillin and streptomycin).

• Restrictive Use:

  • Reserve antibiotics for essential use, avoiding use for viral infections like flu.

Patient Compliance and Resistance

• Importance of Full Course: Completing the full antibiotic course prevents survival and spread of resistant bacteria.

• Consequences of Non-compliance:

  • Stopping early can lead to the proliferation of highly resistant organisms.
  • Risk of spreading resistant bacteria to others.

• Avoid Sharing Antibiotics: Sharing antibiotics leads to inadequate dosing and increased resistance risk.

Visual Aid

• A chart illustrating bacterial population changes during antibiotic treatment highlights the importance of completing the regimen.

Conclusion

• Understanding these resistance mechanisms and proper antibiotic use helps mitigate resistance development.
• Reflect on the importance of adhering to prescribed antibiotic regimens to minimize resistance spread.