Antibiotic Resistance Flashcards
What is resitance?
When a previously suspetible organsims can no longer be killed by an antibiotic at levels which can be sfely achieved clinically
What is intermediate resitance?
Can be treated with an increase from the standard dose
What is the therapeutic index?
The difference between the dose necessary for treatment and that causing harm (usually large)
What is intrinsic resistance?
When all strains of a species are resistant (naturally)
What is the Minimum inhibitory concentration (MIC)?
The lowest concentration of an antibiotic that COMPLETELY inhibits the groeth of a bacterium
What is the Minimum Bactericidal Concentration (MBC)?
The lowest dose that completely kills a bacterium
What is higher the MIC or MBC?
MBC
What is the “antibiotic breakpoint”?
- A concentration chosen for labratory testing that will differentiate sensitive from resistant populations of bacteria
- Allows labratories to test only one concentration rather than having to determine the MIC
What defines the breakpoint?
- Distribution of MICs of target bacteria
- Achievable theraapeutic concentration in tissue
- Maximum achievable concentration
What are streptococci naturally resistant to?
Aminoglycosides
What are Pseudomonas spp. naturally resistant to?
Beta lactams
What are Mycoplasma spp naturally resitant to?
Beta lactam antibiotics
What are enterobacteriaciae resitant to?
Metronidazole
Through which mechanisms can bacteria become resitant?
- Enzymatic inactivation
- Enzymatic addition
- Impermeability
- Efflux
- Alternative pathway
- Altered target
How are enzymes inactivated through destruction?
Beta lactam ring can be hydrolysesd and breaked open
How can enxymes be inactivated through addition?
Aminoglycosides for example can come along and drop acetlyase enzume on tp reducing the drug down to a non-useful form
How do efflux pumps work?
Piece of cellular machinary that actively with ATP can pump antibiotics such as Tetracyclines, Quinolones and Macrolides out of the cell.
- May have an important role in organsims gaining higher levels of resitance
- Tetracyclines, Quinolones, Macrolides
What organism can cause resitance through an aleternative pathway through mec A?
MRSA
What antibiotics can be affected by an altered binding site?
- Rifampicin
- Fluoroquinolones
- Sulphonamides
What can happen as a result of fluoroquinolones being used below their therapeutic index?
Hypermutability
What are the 2 main genes involved in quinolone resitance?
- GyrA and parC
- Mutation of 1 gene encodes low level resistance
- Mutations in both genes encodes a high level of resistance
What antibiotic is the most active fluoroquinolone against 2nd strep s pneumoniae mutants?
Gemifloxacin
How can resitance be transmitted between organisms?
- Transformation (Penicillin in S.pneumoniae) - Conjugation (Beta-lactamases, enterobacteria) - Transposons (Eryhtromycin in S pyogenes)
What is conjugation?
One bacteria shares genetic material to another via a plasmid
What are transpons and integrons?
- Small segments of DNA that encode their own transmission
- Many bacteria have these mobile gentic elements
- Allow genome plasticity
- May collect resistance determinants
What is a MinION?
Handheld device that reads individual bases on DNA which can then help identify bacteria’s genome (type and/or resistance)
What is a superbug?
- An organism that has gained resistnace to a critical drug
- Or an organism that has gained resitance to multiple antibiotics
What are some examples of superbugs?
- MRSA - Methicillin Resistant Staph Aureus
- GISA - Glycopeptide Resistant Staph Aureus
- VRE - Vancomycin Resistant Enterococcus
- ESBLs - Expanded spectrum beta-lactamases
What enzyme can break down carbapenem?
Carbapenamase
What are the 3 major classes of carbapenemases?
- Klebsiella pneumoniae carbapenemase (KPC) requires serine
- New Delhi metallo-betalactamase (NDM) requires zinc
- Oxa-48 group requires serine
What is colistin?
Last resort antibiotic for multi-drug resistant g -ve infections including pneumonia
What infections do we worry about most?
- When the consequences of infection are severe and the organsim is common
- When the organism is naturally resistant to many antibiotics
- When the infection is in a site where it is difficult to get high concentrations of antibiotic
How do we plan on tackiling the problem of antibiotic resistance?
- Optimise the treatment of bacterial disease
- Better diagnosis/diagnostics
- Focussed treatment
- Appropriate length of courses
How are resistant bugs treated?
- Culture essential
- Susceptibility testing
- Use the most bactericidal drug available
- Consider the use of combinations
