Antimicrobials Flashcards
Antibiotic vs. antimicrobial
Antibiotic: substance produced by bacteria, and active against other bacteria
Antimicrobial: substance (either natural or synthetic) that is active against microbes including bacteria, fungi, protozoa
What organisms are most likely to be involved?
-streptococcus
-staphylococcus
-e coli
Treating Streptococcus infections
-Not much resistance
-likely pick Penicillin
Treating E coli
-A lot of resistance
-location will also change the susceptibility reports
eg. In urine, a resistant drug may actually be susceptible
How is it possible to have bacteria that have resistance even though the animals it is found in never had antibiotics?
-Intrinsic resistance- many bacteria already have natural resistance to a lot of antimicrobials
Choosing antimicrobial therapy
- Ask where infection is located?
-easier to treat in urine
-other areas more difficult - Will antimicrobial make it to the site of infection?
eg. CSF, Eye, etc. - Will antimicrobials be effective in pathogens environment?
eg. drug effectiveness in abscess
What is the appropriate drug formulation and dosage regimen?
-keep drug away from hind gut fermentation
-IV infusion (intravenous regional perfusion)- leads to it staying more local
- intraosseous perfusion- caulking gun into joint
-beads at surgical site
-oral dosing- drug goes everywhere, not as efficient at being exactly where it needs to be
Convenia
-may be an appropriate 1st line antibiotic when compliance or administration in doubt
*one dose, lasts longer
*issues: if there is adverse rxn, can’t stop it. Also if there is a short term infection, antibiotics stay in system longer
Testimonial use in antimicrobials
-low quality evidence
-not appropriate, especially when thinking about AMR
Antimicrobial toxicities
-GI effects (vomiting, diarrhea, gut flora changes)
-skin sensitivity
-changes in Blood cells
-organ specific toxicity
*not really hepatotoxicity with antibiotics
Food animals and antimicrobials
-need to be administered safely
-minimize injection site lesions
-stay on label: for example when it says administer dose over 3 sites compared to 1
What factors will play a role in antimicrobial selection?
-cost
-microbe
-pharmacodynamics
-pharmacokinetics
-Risk
-treatment principles
What is the purpose of antimicrobial therapy?
- administer enough dose that it kills all bacteria at site of infection
OR
- Sufficiently suppress so that they can be eliminated by the hosts immune system
Assumptions of high plasma drug concentrations
- large concentration of drug to diffuse into various tissues and body fluids
- Soft tissue infections (wounds, pyoderma)= most bacteria located in extracellular fluid (in equilibrium with plasma)
New macrolide drug plasma concentrations
Have very low plasma concentrations but extremely high tissue concentrations
*bind to leukocytes, carried to site of infection
Minimum inhibitory concentration (MIC)
-lowest drug concentration that inhibits bacterial growth
-dose to reach target plasma concentration of 2-10x the MIC
Minimum Bactericidal concentration (MBC)
-lowest drug concentration to kill 99.9% of bacteria
Mutant prevention concentration (MPC)
-MIC of the least susceptible (ex. more resistant) single=step mutant bacterial population
Antimicrobial susceptibility testing
Resistance= local drug conc < MIC
Intermediate= Local drug conc is equal to MIC
Susceptible= local drug conc > MIC
What is SIR based off of?
-Basedd off of plasma concentrations
**issue is that we don’t know what the actual concentration is at the site of infection. At site of infection could be much higher or much lower
Disk diffusion
-qualitative, not quantitative
-determine zone of inhibition and compare to standards to determine susceptiblity or not
E-test
-expensive
-MIC-like results
-strip filled with antimicrobial (one end high levels, other much less)= provides zone of inhibition or not
Antimicrobial culture and susceptibility testing
-Guides therapeutic decisions
*but does not guarantee drug success or failure
*need to select initial therapy because C&S testing does not come back immediately SO best to know what the likely pathogen and susceptibility is
What does susceptibility not test for?
-host immune system
-drug distribution in body
-drug efficacy in plasma/tissues vs broth/agar
-bacterial growth rates and inoculum size
-mixed infections
-infective environment (debris, pus)
-in vivo antimicrobial synergism
Susceptibility testing limitations
-assumes drug concentrations are only reached via systemic administration
*local administration may have higher concentrations
CLSI-derived veterinary breakpoints
-Not common in vet med
-breakpoints are specific for certain drug and certain pathogen
*estimate, not certain
Future diagnostic approach to determine antimicrobial susceptibility testing
-Use genomics. Find the genes which determine resistance
**may be better than culture and sensitivity testing
Bactericidal
-ratio of MBC to MIC is less than 4-6
eg. possible to obtain concentrations in the patient that will kill 99% of bacteria
Bacteriostatic
-Ratio of MBC to MIC is large
eg. its not safe or feasible to administer enough antimicrobial to kill 99% of bacteria
Bacteriostatic vs. bactericidal
One is not better than the other. Not absolute!!
-the elimination of infection is really based on the immune system
eg. bacteriostatic can kill enough that the immune system can then do its job efficiently
Best predictors of efficacy of bacteriostatic vs. bactericidal
-optimal dosing
-PK
-tissue penetration
**more important than how much the bacteria actually kills
Post Antibiotic effect
Bacterial growth remains suppressed after the antimicrobial concentration has dropped below MIC
-may be reason that dosage regimens effective even with concentrations lower than MIC
**May allow for longer interval between doses
What effects Post antibiotic effect>
-antimicrobial used
-bacteria
Long Post antibiotic effects
-fluoroquinolones
-macrolides
-chloramphenicol
-tetracycline
-aminoglycosides
-metronidazole
Short post antimicrobial effects
-penicillins
-cephalosporins
-trimethoprim/sulphas
Categories of bacterial kill-curves
- Concentration dependent
-Cmax:MIC
want to be at least 10x
-AUC: MIC
bigger exposure relative to MIC, better efficiency; want 125x above MIC - Time dependent
-T>MIC
drugs spend a lot of time above the MIC; half of dosing interval above MIC
Kill curves- concentration dependent
-As concentration goes up, curve gets steeper= kill more bacteria and kill faster
**be aware of how much would be toxic to animal
-Sometimes at a certain point, higher concentration does not really kill bacteria more or faster
-more dose is better
Kill curves- time dependent
-dosing more often is better
*same dose but divided more times/day
-can be unappealing to owners= poor owner compliance
Long acting formulations for time dependent killers
1.Slow absorbing= flip flop
-gets slowly absorbed from injection site
2.high protein binding= convenia
**issue is that sometimes they are sticking around long term but never reach MIC
Antimicrobial dosing
-important in preventing multidrug resistance
Categorization of vet antimicrobials
Category 1: important for human infections; not many drugs that can be used instead of them
Categories 2 & 3: important in human medicine but other options available if resistance occurs
*most vet drugs in category 2
Category 4: low important. Not used in human med at all.
eg. ionophores
