Antibiotic Resistance Flashcards
Why might antibiotic development be stagnant for the last few years?
Lack of monetary gain from antibiotic development
Time required for antibiotic development
Difficulty developing novel antibiotic classes or targets
What is antibiotic resistance?
Organism continues to cause infection despite treatment with antimicrobial –> Leads to therapeutic failure
Antimicrobial is unable to halt growth of organism in vitro due to presence of mutation of acquired gene
How is clinical resistance measured?
Broth dilution
Disk diffusion
E-test
Gene sequencing
Broth dilution
Add fixed amount of bacteria to broth containing a serial dilution of antibiotic
Allow to grow for 16-24 hrs
Determine the lowest concentration of antibiotic that inhibits growth - minimum inhibitory concentration (MIC)
MIC50
Concentration necessary to inhibit 50% of bacteria
MIC90
Concentration necessary to inhibit 90% of bacteria
Disk diffusion
Disks with pre-determined mass of dried antibiotic are placed on an agar dish that has been newly plated with ‘lawn’ of organism
Antibiotic fuses into agar
Where antibiotic concentration in agar is sufficiently high, bacterial growth is inhibited
Resistance is correlated to zone of clearance around disc
Can also be used to test for inducible resistance when 2 disks are placed next to each other
Susceptible VS Resistant
Do the concetrations of given antibiotic attained in human beings achieve concentrations at site of infection that are sufficient to treat pathogen with given MIC?
Yes if considered susceptible. No if considered resistant
If lab MIC is lower than CLSI breaking point, susceptible
If lab dd is higher than CLSI breaking point, susceptible
E test
Gradient of antibiotic concentrations immobilized along rectangular plastic test trip and placed on agar dish that has been newly plated with ‘lawn’ of organism
After 48 hours incubation, a drop shaped inhibition zone intersects graded test strip at MIC
Where did antimicrobial resistance come from?
Resistance genes are ancient and hard wired into microbial pangenome
How to prevent antibiotic resistance?
Reduce prescription of unnecessary antibiotic use
When necessary to treat, choose wisely and deescalate therapy as soon as possible
Reduce transmission of multidrug resistant organisms (hand hygiene, isolation precautions, protocols for central line insertion, remove catheters as soon as possible)