Antibiotics and resistance Flashcards
Describe resistance to ‘last resort’ antibiotics
- Incidence to carbapenems (broad spectrum)
- Klebsiella pneumononiae (50% in some countries resistant)
- Unregulated antibiotics- stricter practice in Scandinavia than in UK
What are the different types of antibiotic resistance?
- ESBLs- extended spectrum beta-lactamases
- MRSA- methicillin resistant S. aureus
- CRE- carbapenem resistant enterobacteriaceae
Give examples of ESBLs
- E.coli resistant to cephalosporin
- K.pneumoniae resistance to cephalosporin
What causes 50% of bloodstream infections?
E.coli
What are the different types of antibiotic function?
- Binding to cell wall- beta lactams and glyopeptides
- Inference with nucleic acid synthesis
- Inhibition of DNA gyrase (folding)- fluoroquinolone (ciprofloxacins)
- Inhibition of ribosomes- bacteriostatic (stuns not kills), aminoglycosides, tetracyclines
- Inhibition of folic acid synthesis (not for pregnancy)
Describe penicillin
- Beta lactam ring
- Bidns to cell wall
- Narrow spectrum
Describe aminopenicillins
- Beta lactam ring
- Bind to cell wall
- Broad spectrum
- E.g. flucloxacillin
- Does not treat staphylococci
Describe extended-spectrum penicillins
- Beta lactam ring
- High potency
- Even against pseudomonas
Describe cephalosporins
- Beta lactam ring
- High potency
- Broad spectrum
- Cell wall binding
Describe carbapenems
- Beta lactam ring
- High potency
- Bind to cell wall
What are the beta-lactamase inhibitor combinations?
- Co-amoxicillin
- Tazocin
Describe macrolides
- Work against ribosomes
- Gram pos and neg
- Intracellular
Describe trimethoprim
- Folic acid inhibitor
Describe fluroquinolones
- DNA gyrase inhibitor
- Broad spectrum
Describe vancomycin
- Glycopeptide
- Binds to cell wall and works against MRSA
What are the mechanisms of antibiotic resistance?
- Specific enzymes that inactivate antibiotics
- Modified bacterial cell wall envelope that makes them impermeable to antibiotics
- Expulsion by efflux system
- Modified target, therefore binds less avidly
- Antibiotic mechanism bypassed by changing metabolic pathway
Describe enzyme inactivation as a method of AR with beta lactamase
- Commonest and most clinically significant
- Staph cocci adaptation- penicillinase
- Gram negative developed aminopenicillin resistance
- Haemophilus influenzae (in children) developed resistance to aminopenicillin
Describe enzyme inactivation as a method of AR with cephalosporins
- Extended spectrum Beta lactamases (ESBL)
- Klebsiella and E.coli resistance to cephalosporins
Describe enzyme inactivation as a method of AR with carbapenems
- Pseudomonas
- E.coli
- Klebsiella resistance against meropenem
Describe impermeability as a method of AR
- Porins in bacterial cell walls (channels)
- Pseudomonas has porin-deficient cell wall
- Resistance to carbapenems
Describe efflux as a method of AR
- Pseudomonas and E. coli
- Expulsion of antibiotic from the cell
Describe target alteration as a method of AR
- Antibiotic cannot bind as well
- Strep pneumoniae
- Pneumonia, meningitis and ear infections
- Changing penicillin binding proteins
- MRSA (MecA- gene- changes S. cocci cell wall which stops flucloxacillin from binding)
Describe bypass as a method of AR
- Vancomycin (glycopeptide- VRSA)
- S.aureus uses a different pathway to synthesise cell wall
- Enzymatic pathway to repair and contain lysis
- E.g. VanA
Describe bacterial genetics
- mRNA synthesis
- mRNA to ribosome to protein synthesis
- Chromosome can undergo alteration
- Mutation can occur every 20 minutes
- Spontaneous change in DNA (e.g. in TB)
Describe mobile genetic elements
- Plasmids
- Circular- contain at least one gene
- > Traffic outside bacterium
- > Open reading frames that allow self replication
- > Antibiotic resistance gene on plasmid
- Conjugate- bacteria can share resistance
- > Interspecies sharing is also possible
What are factors that encourage antibiotic resistance?
- Using antibiotics when unnecessary (rapid and accurate diagnosis can reduce this)
- Using ‘broad-spec’ when narrow spectrum works
- Using a longer course than necessary
- Agricultural and industrial use
