L44: Antimicrobials And Immunization Flashcards
Main groups of antibacterial agents
- Beta-lactams: penicillin, cephalosporin, monobactam, carbapenem
- Aminoglycosides: gentamicin
- Macrolides: erythromycin, clarithromycin
- Tetracycline: doxycycline
- Fluoroquinolones: ciprofloxacin, levofloxacin
- Sulphonamides: sulfamethoxazole
- Glycopeptide: vancomycin
- Oxazolidinone: linezolid
Targets for antimicrobial
- Peptidoglycan: Betalactam, Vancomycin, Bacitracin
- Protein synthesis:
30s inhibitors: Tetracycline, Aminoglycosides
50s inhibitors: Macrolides, Clindamycin, Linezolid, Chloramphenicol - Folate synthesis: Sulphonamides, Trimethroprim
- DNA gyrase: Fluoroquinolone
- DNA dependent RNA polymerase: Rifampicin
Mechanisms of beta-lactam
Covalently bind to and inhibit transpeptidase/penicillin binding protein (PBP)
—> inhibit pentapeptide cross linking between NAM subunits
—> bacterial cell wall weakens
—> autolysin activated to destroy existing cell wall / osmotic lysis
MBC vs MIC
MBC: minimal bactericidal concentration = lowest concentration of antimicrobial that kills initial bacterial inoculum by 99.9%
MIC: minimal inhibitory concentration = lowest concentration of antimicrobial that prevent visible growth of bacteria
Mechanisms for antibiotic resistance
- Reduced permeability to antimicrobial (Porin mutation)
- Increased efflux (efflux pump: abolished transcriptional repressor/synthesis of efflux pump protein)
- Modification of antibiotic target
- PBP modification, Ribosomal protein methylation
- by mutation/ horizontal gene transfer - Modification of antibiotic (Beta-lactamase, aminoglycoside modifying enzyme)
Beta lactamases
Gram +ve: extracellular
Gram -ve: periplasm (between LPS and peptidoglycan)
What is Immunization and vaccine
Immunization: artificially inducing immunity to provide protection from disease
Vaccine: antigenic preparation used to induce immunity
Types of vaccine
- Live attenuated
- virus (MMR, varicella-zoster)
- bacteria (BCG) - Inactivated
- whole virus (polio, influenza)
- whole bacteria (pertussis) - Fractions
- toxoids
- polysacchaide
- conjugates
- protein subunits
Active immunisation
- Induction of acquired immunity by priming with antigen
- Production of specific antibody and T lymphocyte
Benefits and problems with live attenuated vaccine
Benefits
- Mimic natural infection
- protect unvaccinated —> herd immunity
Problems
- Reversion to virulence
- In immunocompromised patients: person-to-person transmission
How, When to use and problems with inactivated vaccines
How
- Heat (Vibrio Cholera)
- Chemical
- formaldehyde (Hep A)
- beta-propiolactone (influenza)
When
- Impossible to attenuate, can only kill
- Risky strain
- Unknown stability / risk of reversion
Problems
- Less immunogenic
- Poorer stimulation of memory cells
- Shorter duration of protection
How to improve immunogenicity
- Adjuvant: aluminium salts to boost immune response, non-specific, effective in inducing antibody response but less in inducing cell-mediated immunity
- Protein conjugation: polysaccharide capsule/antigen conjugated to protein carrier to improve response and allow T cell to participate —> call for more memory B cells and plasma cells
Difference in vaccination scheme
- Availability, efficacy, safety of vaccine
- Disease burden
- Availability of treatment (if available then less need for vaccine)
- Cost-effectiveness
Passive immunisation and its problems
- Administration of exogenously produced antibody / memory T cell
- provide immediate but short-lasting protection
- prophylaxis / replacement therapy
- for those unable to respond immunologically
- e.g. pooled human immunoglobulin, specific immunoglobulin (all from donor)
Problems
- Short-lasting
- Serum sickness
- Risk of bloodborne infections
