antibiotic resistance Flashcards
What do bacteriostatic antibiotics do?
Inhibit bacterial growth by inhibiting protein syntheses, DNA replication and metabolism
Also reduce exotoxin production and endotoxin surge less likely from gram -ve bacteria
What do bactericidal antibiotics do?
Inhibit cell wall synthesis causing death of bacteria
When are bactericidal antibiotics very useful?
Poor tissue penetration (e.g. Endocarditis)
Difficult to treat infections (e.g. TB)
Need to eradicate infection quickly (e.g. meningitis)
What is required for a bacteriostatic antibiotics to work?
Minimum inhibitory concentration (MIC) MIC:MBC ratio >4
What is required for bactericidal antibiotics to work?
Minimum bactericidal concentration (MBC)
What does concentration dependent killing depend on?
The height of concentration above the minimum inhibitory concentration (MIC)
Peak concentration/MIC ratio
What does time dependent killing depend on?
On time the concentration stays above the minimum inhibitory concentration for
t>MIC
Give an example of an antibiotic group that uses concentration dependent killing
Aminoglycosides
quinolones
Give 2 examples of a antibiotic groups that uses time dependent killing
Beta lactams
Macrolides
clindamycin
Name 4 mechanisms of antibiotic resistance
- target site mutation
- Destroy or inactivate antibiotic
- Prevent antibiotic access
- Remove antibiotic from bacteria
how does target site mutation cause antibiotic resistance?
Changes molecular configuration at antibiotic binding site or masks it
Flucloxacillin is no longer able to bind to PBP of Staphylococci in MRSA
Give 2 examples of the destroy/inactivate antibiotic mechanism of antibiotic resistance
- Beta lactamase hydrolyses beta lactam ring so it can no longer bind to PBP
- Staph producing penicillinase so penicillin but flucloxacillin is inactivated
how does removal of antibiotic cause antibiotic resistance?
Export pumps remove the antibiotic so the level of antibiotic is reduced
- S. aureus and S. pneumoniae resistant to fluoroquinolones
- Enterobacteriaceae resistance to tetracyclines
By what 2 ways can antibiotic resistance develop?
- Intrinsic (naturally resistant)
2. Acquired
Give 3 examples of intrinsic antibiotic resistance development
- Gram -ve outer membrane can’t be penetrated by vancomycin
- Enterococci PBP are not effectively bound by cephalosporins
- Aerobic bacteria enable to reduce metronidazole to its active form
what are the 2 ways that acquired antibiotic resistance can occur?
- Spontaneous mutation
2. Horizontal gene transfer
How can acquired spontaneous mutation antibiotic resistance come about?
- New nucleotide base pair
- Change in aa sequence
- Change to enzymes to cell structure
- Reduced affinity or activity of antibiotic
Cause altered enzyme function leading to reduced antibiotic effect
Give and briefly explain the 3 types of horizontal gene transfer antibiotic resistance
- Conjugation - sharing of extra-chromosomal DNA plasmids (‘bacteria sex’)
- Transduction - insertion of DNA by bacteriophages
- Transformation - bacteria takes up free DNA
Name 2 important gram +ve antibiotic resistant organisms
- Methicillin resistant Staphylococcus Aureus (MRSA)
2. Vancomycin Resistant Enterococci (VRE)
How has MRSA gained antibiotic resistance?
- Staphylococcal cassette chromosome med (SSCmec) contains resistance gene mecA
- Encode penicillin-binding protein 2a (PBP2a) that does not bind to penicillin
- Confers resistance to beta lactam antibiotics as well as Methicillin
How has vancomycin-resistant enterococci (VRE) gained antibiotic resistance?
Plasmid mediated acquisition of gene encoding altered aa on peptide chain preventing vancomycin binding
Promoted by cephalosporin use
Name 3 important gram -ve antibiotic resistant types
- b-lactamase enzymes hydrolysing penicillins
- Extended spectrum beta lactamase (ESBL)
- AmpC b-lactamase resistance
Give 3 examples of b-lactamase enzymes hydrolysing penicillins
TEM-1 in E. coli, H. influenzae and N. gonorrhoea
SHV-1 in K. pneumoniae
CTX_M cephalosporinase in enterbacteriaceae
What, typically, are b-lactamase enzymes hydrolysing penicillins sill sensitive to?
Extended spectrum beta lactamase (ESBL) inhibitors due to a further mutation at active site
