Magic Bullets - Antibiotics Flashcards
Describe the selective toxicity of penicillins.
In the absence of allergy, penicillins have very low toxicity and high doses can be used.
Describe the selective toxicity of aminoglycosides.
Aminoglycosides have a narrow therapeutic index, thus the dose that causes toxicity is very close to the therapeutic dose.
What is resistance?
- Resistance is when a previously susceptible organism is no longer inhibited by an antibiotic at levels that can be safely achieved clinically.
- Intermediate resistance can be treated with an increase from the standard dose.
What is the therapeutic index of a drug?
The difference between dose necessary for treatment and that causing harm is usually large and is known as the therapeutic index.
What is intrinsic resistance?
Intrinsic resistance is when all strains of a species are resistant.
What is the minimum inhibitory concentration (MIC) of an antibiotic?
Minimum inhibitory concentration (MIC) is the lowest concentration of an antibiotic that completely inhibits the growth of a bacterium.
What is the minimum bactericidal concentration (MBC) of an antibiotic?
The minimum bactericidal concentration (MBC) is the lowest dose that completely kills a bacterium.
Describe what an antibiotic break point is.
- A concentration chosen for laboratory testing that will differentiate sensitive from resistant populations of bacteria.
- The breakpoint for a given antibiotic will vary for each of the species tested due to their differing intrinsic resistance / susceptibility.
- Used to simplify testing in the laboratory.
- Allows laboratories to test only one concentration rather than having to determine the MIC.
Describe the relationship between streptococci and aminoglycosides.
Explain this.
- Streptococci are naturally resistant to aminoglycosides.
- This is because the MIC is above the concentration that causes toxicity.
Describe the relationship between Pseudomonas spp. and beta lactams.
Explain this.
- Pseudomonas spp. are normally resistant to beta lactams.
- This is because pseudomonas spp. have intrinsic betalactamases, but can be overcome design.
Describe the relationship between mycoplasma spp. and beta lactam antibiotics.
- Mycoplasma spp. are all resistant to beta-lactam antibiotics.
- This is because the mycoplasm cell wall has no peptidoglycan.
Describe the relationship between enterobacteriaciae and metronidazole.
- Enterobacteriaciae are all resistant to metronidazole.
- This is because they are facultative anaerobes - they grow in aerobic conditions.
What is acquired resistance?
Acquired resistance occurs when a previously susceptible strain or species develops an increase in the MIC that takes it beyond the therapeutic range.
Give examples of resistance mechanisms and an example of the antibiotics which they cause resistance to.
- Enzymatic inactivation
- E.g. β-lactamases
- Enzymatic addition
- E.g. Aminoglycosides
- Impermeability
- E.g. β-lactams
- Efflux
- E.g. Tetracyclines
- Alternative pathway
- E.g. MRSA mecA
- Altered target
- E.g. Rifampicin
What is resistance evolution?
- Development of resistance through mutation in critical chromosomal genes.
- Critical genes involved that are the target of the antibiotic.
- Examples include rifampicin, DNA gyrases.
Describe the evolution of quinolone resistance.
- There are two genes involved in gyrA and parC.
- Point mutations in the genes change the affinity of the proteins for DNA.
- Mutation in one gene encodes low level resistance.
- Mutation in both genes encodes high level resistance.
What are the forms of resistance transmission?
- Transformation - altered gene with altered affinity for product.
- E.g. penecillin in S. pneumoniae
- Conjugation
- E.g. β-lactamases, Enterobacteria
- Transposons - small segments of DNA that encode their own transmission.
- E.g. erythromycin in S. pyogenes
