Infections Lecture 3: Bacterial Resistance to Antibiotics Flashcards
How does inherent (natural) resistance to bacteria work?
- Gram negative outer membrane provides a permeability barrier
- It stops sufficient amounts of antibiotic from entering cell to exert its action
How does acquired resistance work?
- A new antibiotic used and most infections then respond
2. Over time treatment fails as resistance is acquired
What are the two ways acquired resistance works?
- Changes in the bacterial genome
- Mutation and Selection: Vertical Evolution
- Exchange of genes between strains and species: horizontal evolution
What is vertical evolution?
- Spontaneous mutation that confers resistance
- Happens in the absence of antibiotics
- Drug does not induce resistance
- Better adapted survive and thrive - All bacterium die and resistant bacterium stays alive to replicate
What is horizontal evolution?
- Bacteria acquire resistant genes from other bacteria
- Swap genes by:
- conjugation: Cell to cell contact, DNA crosses a sex plus
- Transduction: genes transported by bacterial virus
- Transformation: DNA acquired from environment
Give examples of how the conversion of active drug to inert product by an enzyme occurs? (common)
- Gram positive and negative cells can produce beta-lactamase
- Converts Penicillin to penicilloic acid (not antibacterial) - Aminglycosides can be inactivated by acetyl/adenyl/nucloetidyl transferases
- Chloramphenicol (broken by acetylation) (chloramphenicol acetyl transferase)
What is the reduction in cellular permeability to antibiotic?
- Doesn’t allow drug to get to toxic levels in cell
- Change in cell wall and membrane which antagonises antibiotic transport processes (generation of efflux pump)
- Some species pump tetracycline out of cell
Give examples of how changes in the antibiotic target site results in resistance and acquisition resistant form of target enzyme?
- Example: Ribosomes are targeted for erythromycin (modified to prevent binding) (S.aureus)
- Penicillin binding proteins on cell wall which prevented methicillin action also known as MRSA
- Resistance to quinolones due to changed structure of target enzyme DNA gyrase
What are the four mechanisms of actions of bacterial resistance?
- Conversion of active to inert by enzyme
- Reduction in cellular permeability to antibiotic
- Changes to antibiotic target site resulting in resistance
- Altered metabolic pathway
Give an example of how an altered metabolic pathway works?
Trimethoprim resistance when E.coli has its metabolic pathway altered from UTI treatments
How does clostridium difficile emerge?
- Use of antibiotics kill the normal gut flora
2. C. difficile takes over to release toxins
Describe the Glycopoetide Resistant Enterococci and how it obtains its resistance?
- Gram postive cocci
- Enteric: normally found in digestive and urinary that
- Intrinsically resistant to many antibiotics: PBP (penicillin binding protein) bind less well to beta lactams
- Conjugation: acquires the resistance by conjugation (acquired beta lactase)
What does Glycopoetide Resistant Enterococci commonly cause?
Wound infections
Bacteraemia
Abdominal and pelvic infections
Particular problem in immuno-compromised
What is the Carbapenem Resistant Enterobacteriaceae, what are its common names and what are the treatment options?
- Enterobacteriaceae: Gram Negative Bacilli
- Part of gut flora or can be found in soil and water
- Resistant to ost or all available antibiotics
- Most commonly e. coli or salmonella
- Treatment options: Polymyxins, Tigecycline, fosfomycin and aminoglycosides
What is TB?
- Mycobacterium Tuberculosis
2. Contagious infectious lungs
