Antibiotic Resistance Flashcards
Define resistance.
a previously susceptible organism is no longer inhibited by an antibiotic at levels that can be safely achieved clinically (causes MIC to rise)
Define intermediate resistance.
Resistance which can be treated with an increase from the standard dose.
Define therapeutic index.
Difference between dose necessary for treatment, and minimum dose causing harm.
Define intrinsic resistance.
All strains of a species are resistant (regardless of dose of antibiotic)
Define minimum inhibitor concentration (MIC) + minimum bactericidal concentration (MBC).
Lowest concentration of an antibiotic that completely inhibits the growth of a bacterium.
Lowest concentration of an antibiotic that completely kills a bacterium.
What is the MBC of bacteriostatic drugs ?
They do not have one (they do not kill the bacteria)
Describe a method to determine the MIC and MBC of a drug.
TUBE METHOD
- Antibiotic added in increasing concentration in medium inoculated with bacterial cells.
- MIC is first clear tube
- Then, transfer content of each clear tube including and following the MIC tube to fresh medium containing no antibiotic.
- First clear tube at that point is the MBC
Define antibiotic breakpoint. What factors might change the antibiotic breakpoint.
- Concentration chosen for laboratory tests which will differentiate sensitive from resistant populations of bacteria (makes it easier for labs, allows them to test only one concentration rather than having to determine the MIC)
- The breakpoint of a given antibiotic will be different for different species because they will have different intrinsic resistance/susceptibility.
What are the factors which determine the breakpoint of an antibiotic.
- The distribution of MICs of the target bacteria
- Achievable therapeutic concentration in tissue (i.e. because if the breakpoint is at a toxic dose, then breakpoint needs to be reduced)
- Maximum achievable concentration
Identify organisms with intrinsic resistance, and identify the classes of antibiotics each is resistant to and the reason they are resistant.
Streptococci are naturally resistant to aminoglycosides (because their MIC is higher than the toxic concentration)
Pseudomonas spp. normally resistant to beta-lactams (because intrinsic beta lactamases, although these can be overcome by design)
Mycoplasma spp. are all resistant to beta lactams (because no peptidoglycan in cell wall, which beta lactams act against)
Enterobacteriacae are all resistant to metronidazole (because they are facultative anaerobes, so normally grow in aerobic conditions)
Define acquired resistance.
Previously susceptible species or stain develops an increased MIC which takes it beyond therapeutic range.
Identify the main mechanisms of resistance.
1) Enzymatic inactivation by destruction
2) Enzymatic inactivation by addition
3) Efflux
4) Alternative pathway
5) Altered target
Identify an enzyme responsible for the process of enzymatic inactivation by destruction. Identify a class of antibiotics affected by this.
Beta lacatamases
Expanded spectrum beta lactamases
Beta lactams (including cephalosporins) are effected by this.
Identify a class of antibiotics affected by the process of enzymatic inactivation by addition.
Aminoglycosides
Describe the process of efflux. Identify an antibiotic affected by the process by efflux.
“Efflux pumps are transport proteins involved in the extrusion of toxic substrates (including virtually all classes of clinically relevant antibiotics) from within cells into the external environment.” Mechanism of resistance which may have a role in organisms gaining higher levels of resistance.
Affects tetracyclines, quinolones, macrolides.