Antibiotic Resistance Flashcards
What is resistance?
When a previously susceptible organism is no longer inhibited by an antibiotic at levels that can be safely achieved clinically
How would you treat intermediate resistance?
increase of the standard dose
What is the therapeutic index?
the difference between the dose necessary for treatment and the dose that causes harm
What is intrinsic resistance?
When all strains of a species are naturally resistant
What is MIC and MBC?
- MIC: minimum inhibitory concentration is the lowest concentration of an antibiotic that completely inhibits growth of bacterium
- MBC: minimum bactericidal concentration is the lowest dose that completely kills a bacterium (always higher than MIC)
What is antibiotic breakpoint?
- concentration chosen for laboratory testing that will differentiate sensitive from resistant populations of bacteria
- varies for each species
Why are antibiotic breakpoints used?
- to simplify testing
- to allow labs to test only one concentration rather than having to determine the MIC
What defines antibiotic breakpoint?
- distribution of MICs of target bacteria
- achievable therapeutic concentration in tissue
- maximum achievable concentration
What are some examples of intrinsically resistant bacteria?
- streptococci are resistant to aminoglycosides (MIC > conc. that causes toxicity)
- pseudomonas spp. are resistant to B-lactams (produces B-lactamases)
- mycoplasma spp. resistant to all B-lactam antibiotics (has no effect as they do not have peptidolglycan)
What is acquired resistance?
when a previously susceptible strain or species develops an increase in MIC that takes it beyond therapeutic range
What are the resistance mechanisms?
- enzymatic inactivation
- enzymatic addition
- impermeability
- efflux
- alternative pathway
- altered target
What are examples of bacteria that become resistant by enzyme inactivation and their mechanism?
- hydrolyses it which inactivates it
- eg. B-lactamases, cephalosporins, and expanded spectrum B-lactamases
What are examples of bacteria that become resistant by enzyme addition and their mechanism?
- adds adenylases/phosphorylases/acetylases which inactivates it
- eg. aminoglycosides
What are examples of bacteria that become resistant by efflux pumps?
- tetracyclines
- quinolones
- macrolides
- can contribute to organisms gaining a higher level of resistance
What are examples of bacteria that become resistant by alternative pathways and their mechanism?
- flucloxacillin
- precursors are converted to peptidoglycan through a Mec A product instead of through penicillin binding proteins
What are examples of bacteria that become resistant by an altered binding site?
- rifampicin
- fluoroquinolones
- sulphonamides
Describe the evolution of quinolone resistance
- 2 genes involved GyrA and parC
- point mutations change affinity of proteins for DNA
- mutation in one gene encodes low resistance
- mutation in both genes encodes high level resistance
What are the resistance transmission mechanisms?
- transformation (altered gene with altered affinity for product eg. penicillin/S.pneumoniae)
- conjugation (plasmids shared between bacteria, can encode resistance determinants eg. B-lactamases)
- transposons (small segments of DNA that encode their own transmission that can collect resistance determinants eg. erythromycin in S.pyogenes)
What is a superbug and examples?
- organism that has gained resistance to a critical antibiotic
- organism that has gained resistance to multiple antibiotics
- eg. MRSA/GISA/VRE
What are the carbapenemases and their active sites?
- KPC (serine)
- NDM (zinc)
- Oxa-48 group (serine)
Describe how carbapenemases cause resistance and the bacteria it is active against
- by transmission of plasmid (conjugation)
- KPC: cephalosporins/aztreonam/carbapenems
- NDM: cephalosporin/BL/BLI/carbapenems
- Oxa-48: 1-3rd generation cephalosporins, variable against 4th/BL/BLI/carbapenems
When do we worry about resistant bacteria?
- when consequences of infection are severe and organism is common (MRSA)
- when organism is naturally resistant to many antibiotics (Ps.aeruginosa)
- when the infection is in a site where it is difficult to get high concentrations of antibiotic (pneumococcal meningitis)
How is bacterial resistance addressed?
- optimise treatment of bacterial disease
- better diagnostics/diagnosis
- focused treatment
- appropriate length of courses
How are resistant bugs treated?
- culture
- susceptibility testing
- use most bactericidal drug available
- consider use of combinations
