In-Depth Notes on Antibiotics and Antibiotic Resistance II

Antibiotics and Antibiotic Resistance II

Lecture Outline
  • Antibiotic resistance - definitions
  • The impact of antibiotic resistance on global health
  • Evolution and spread of antibiotic resistance
  • Antibiotic resistance mechanisms & clinically important examples
Learning Outcomes
  • Outline the current concern about the rise of antibiotic resistance.
  • Describe how resistance can arise and spread in bacteria.
  • Explain key resistance mechanisms for common antibiotics.
Recommended Reading
  • Prescott’s Microbiology, Chapter 9.
  • Fighting Antimicrobial Resistance, Edited by Ana Budimir (Open Access, 2018).
  • Blair et al., Molecular Mechanism of Antibiotic Resistance, Nature Reviews Microbiology, Volume 13, Pages 42–51 (2015).
What is Antibiotic Resistance?
  • Definitions according to EUCAST:
    • S (Susceptible): High likelihood of therapeutic success using standard doses.
    • I (Susceptible, increased exposure): High likelihood of success with adjusted dosing.
    • R (Resistant): High likelihood of therapeutic failure even with increased exposure.
Antibiotic Resistance, Tolerance, and Persistence
  • Antibiotic Tolerance: Reduced susceptibility to bactericidal antibiotics due to low target activity or low drug uptake.
  • Antibiotic Persistence: Refers to a subset of tolerant cells that survive antibiotic treatment, not genetically different from the susceptible population.
Host-Induced Persistence
  • Intracellular lifestyles can protect and increase the survival of antibiotic-resistant bacteria/persisters.
Impact of Antibiotic Resistance on Human Health
  • Rapid emergence of antibiotic resistance after drug introduction (e.g. Tetracycline, Penicillin, Vancomycin).
  • Global health threat due to multi-drug resistant (MDR) strains.
  • Example: Increase of MDR Klebsiella pneumoniae (2005-2014).
Multi-Drug Resistant Bacteria of Concern
  • Critical Group:
    • Acinetobacter baumannii, Neisseria gonorrhoeae, MRSA, Klebsiella pneumoniae.
  • XDR typhoid outbreak in Pakistan: more than 5,200 cases reported.
Why Study Bacteria in Health & Disease?
  • Bacteria are essential for healthy living and among the leading causes of human death.
  • Antibiotics save millions of lives every year.
  • Understanding bacterial resistance mechanisms is crucial to prevent antibiotic misuse.
Evolution and Spread of Antibiotic Resistance
  • Intrinsic Resistance: Natural absence of antibiotic target in the organism.
  • Evolved Resistance: Occurs due to mutations under antibiotic selection pressure.
  • Acquired Resistance: Result of horizontal gene transfer mechanisms.
Mechanisms of Resistance
  • Enzymatic Inactivation: e.g. β-lactamases.
  • Impermeability: Alteration of membrane permeability reduces drug influx.
  • Efflux: Antibiotics are pumped out of the cell via transporters.
  • Target Modification: Changes in antibiotic target sites lead to resistance (e.g. mutations in PBPs).
  • Alternative Pathways: Development of bypass mechanisms (e.g. MRSA).
Take Home Messages
  • The healthcare system faces a significant threat from antibiotic resistance.
  • Multiple pathogens are becoming resistant to available treatments, stressing the need for new antibiotics and diagnostics.
  • Understanding and mitigating resistance mechanisms is imperative for public health and safety.
Contact Information
  • Dr. Gunnar N. Schroeder
    Room: 3.021, Wellcome-Wolfson Institute for Experimental Medicine
    Email: g.schroeder@qub.ac.uk