Hospital acquired infection and antibiotic resistance Flashcards
What is the breakpoint?
The concentration of antibiotic that can be achieved in a clinical setting
If the bacteria can divide at a concentration at or higher than the breakpoint, it is deemed resistant
Name some major antibiotic resistant Gram-negative bacterial pathogens.
- Pseudomonas aeruginosa
cystic fibrosis - Klebsiella
GI infection - Salmonella
GI infection, typhoid fever - Acinetobacter baumanii
UTI, wounds - Neisseria gonorrheae
gonorrhoea
Name some major antibiotic resistant Gram-positive bacterial pathogens.
- Staphylococcus aureus (MRSA)
wound and skin infection - Streptococcus pneumoniae
pneumonia - Clostridium dificile
diarrhoea, colitus - Enterococcus spp.
UTIs, bacteremia
Name 7 types of antibiotic.
Beta-lactams Aminoglycosides Chloramphenicol Tetracycline Quinolones Sulphonamides Macrolides
How do beta-lactams work? Give some examples.
- Penicillin and Methicillin
They have a beta-lactam ring of similar structure to the precursor of peptidoglycan and hence interferes with the synthesis of the peptidoglycan cell wall
- Binds to Penicillin Binding Proteins (PBP) - they catalyse a number of steps in
peptidoglycan synthesis
How do quinolones work?
Quinolones inhibit the functioning of DNA gyrase (Gram-negative) and topoisomerase (Gram-positive) hence hampering the unravelling of DNA during replication
How do macrolides work? Give an example.
- Only Gram-positive infections
- Targets the 50S ribosomal subunit and prevents the aminoacyl transfer step so there is no peptide bond
- Erythromycin
How do aminoglycosides work? Give some examples.
- bactericidal
- affects protein synthesis
- affects RNA proofreading which leads to misfolded proteins
- Some of these proteins are incorporated into the membrane and allow leakage
so the cells rupture. - hs some issues with being toxic
How do sulphonamides work?
- bacteriostatic
- used to treat UTIs
- interferes with the folate pathway
How does tetracycline work?
- bacteriostatic
- inhibits protein synthesis
- Prevents charged amino-acyl tRNAs from binding to the mRNA/ribosome complex
- prevents the elongation of the polypeptide
How does chloramphenicol work?
- Bacteriostatic
- Inhibits the peptidyl transfer step of protein synthesis
- Binds to the 50S subunit and blocks the peptidyl transfer step
What are the four main mechanisms of antibiotic resistance?
- Altered target site
- Inactivation of antibiotic
- Altered metabolism
- Decreased drug accumulation
what is bacteriostatic?
inhibits the growth of bacteria
what is resistance?
the ability of an organism to replicate in the presence of an antibiotic at a particular concentration
what is MIC? (minimal inhibitory concentration)
the lowest concentration of the antibiotic required to inhibit growth
what were misconceptions formed at the dawn of the antibiotic era?
- Resistance against more than one class of antibiotics could not occur
- There is no horizontal gene transmission
- Resistant organisms would be significantly less ‘fit’
what is an exception to resistance of an antibiotic developing quickly?
why?
Erythromycin and Vancomycin
Vancomycin - is toxic and not hugely effective so it wasn’t used much at the
time of discovery so it took longer for resistance to develop
what is the general mechanism of action of antibiotics?
Antibiotics generally tend to inhibit processes that are unique to bacteria -
SELECTIVE TOXICITY
explain how altered active site gives rise to resistance?
- the target site can change with a new gene that encodes for a target modifying enzyme
- the new gene might have the same function but a new structure so it does not respond to the new antibiotic
how does MRSA have an altered target site?
MRSA acquired a gene, which produces an alternative penicillin binding protein - it performs the same function but has lower affinity to beta- lactams so methicillin is ineffective.
how is Streptococcus pneumoniae resistant?
Streptococcus pneumoniae is resistant to erythromycin because it has acquired a gene which encodes an enzyme that methylates the AB target site in the 50S ribosomal subunit - this changes its structure
how does the inactivation of the antibiotic work?
- Acquire gene for an enzyme which breaks down the antibiotic
- eg. beta-lactamase (bla)
how is the metabolism altered?
- Re-engineer the metabolic pathways so you bypass the step that the antibiotic interferes with.
- increased production of enzyme substrate can be used to outcompete antibiotic inhibitor
how does decreased drug accumulation work?
- Reduced permeability of Antibiotic into bacterial cell
- Increase EFFLUX of antibiotic out of cell
- the drug does not reach a sufficient concentration to be effective
