Module 25 - Antibiotics Flashcards
Describe how antibiotics are classified.
- Source
- Mechanism of Action (Target)
- Spectrum
- Chemical Structure
Differ the effects of bacteriostatic and bactericidal antibiotics n bacterial growth in vitro.
Describe the three determinants of antimicrobial action in vivo.
- Selective Toxicity
- Exploiting differences in structure and metabolism of the bacterium and host cell.
- Access to the site of infection
- achieve adequate levels where the organism is
- Provision of appropriate levels for an appropriate time
- maintain adequate levels to allow inhibition or killing
These factors determine whether an organism will be “sensitive” or “resistant” to an antimicrobial.
Describe the mechanism of Vancomycin (glycopeptides).
It binds to the terminal D-ala-D-ala residue of the peptidoglycan, preventing the incorporation of the NAG-NAM subunit into the growing peptidoglycan chain.
They are administered through injection, not orally. Only effective with gram-positive organisms.
Explain the mechanism of resistance to glycopeptides.
- Alteration of Target: mutation of terminal D-ala-D-ala to D-ala-D-lactate in enterococci, disallowing binding to the sequence
- Production of excess target (peptidoglycan) in Staphylococci.
Describe the mechanism of how beta-lactam antibiotics.
The antibiotics interfere with the transpeptidases (penicillin-binding protein) which are responsible for the cross-linking of peptidoglycan in the bacterial cell wall.
This is achieved as beta-lactams is structurally similair D-ala-D-ala - the terminal amino acid residues on the precursor NAM/NAG-peptide subunits of the nascent peptidoglycan layer. Effective with both gram-positive and gram-negative bacteria.
Explain how some bacterial strains are resistant to beta-lactam antibiotics.
They possess beta-lactamase enzyme which breaks down the beta-lactam ring of the antibiotics, which is crucial for its function.
Some strains may also alter penicillin-binding proteins (transpeptidases), which still maintains its function of building up peptidoglycan, but disallowing binding and deactivation by beta-lactam antibiotics.
Describe the mechanism of aminoglycosides.
They inhibit the association/recognition of the mRNA with the 30S ribosome, leading to the misreading of the mRNA code. It is bactericidal in nature.
The spectrum of this antibiotic is against aerobic, gram-negative bacteria (also allows gram-positive). Considerable toxicity.
Examples include gentamicin, tobramycin, amikacin.
Describe the resistance mechanism for aminoglycosides
- Aminoglycosides have many functional groups that can be readily modified by the bacteria. These enzymatic modifications may lead to a reduced entry of the antibiotics into the bacterium.
- Modifications on the outer membrane may also lead to reduced entry.
- Modifications (to aminoglycoside or outer membrane) to increased efflux of antibiotics.
- Ribosomal mutation leading to reduced binding.
Recap all the resistance mechanisms to general antimicrobial agents
- Drug inactivation
- By hydrolysis, e.g. β-lactams
- By covalent modification, e.g. aminoglycoside, chloramphenicol
- Altering the target of drug action
- Modify target to a less sensitive form, e.g. β-lactam
- Overproduce target, e.g. vancomycin
- Reduce access of drug to target
- Reduced entry into cell, e.g. aminoglycosides
- Increase efflux from cell, e.g. aminoglycosides
- Failure to activate the inactive precursor of a drug
- e.g. metronidazole
Mention the basic mechanism of metronidazole.
It is administered initially as an inactive precursor form before being activated by the microorganism.
Describe the genetic basis behind resistance.
Intrinsic
- cell wall impermeability (vancomycin and G -ves)
- lack of target (Mycoplasma - no cell wall; enterococci - unable to synthesise folic acid)
- chromosomal resistance gene (Pseudomonas beta-lactamase)
Acquired
- horizontal gene transfer (e.g. bacteriophages, plasmids)
- mutation
Mention the methods of bacterial DNA transfer.
