Lec 5-6 Micro Tx Staph Strep Flashcards
What is pharmacokinetics?
“what the body does to the drug”
- absorption, distribution, metabolism, elimination
What is pharmacodynamics?
“What the drug does to the body [or organism]”
What does it mean if an antimicrobial is concentration-dependent?
- increase in concentration causes increase in rate of bacterial killing
3 examples of concentration-dependent antibiotics?
- daptomycin [lipopeptides]
- aminoglycosides
- fluoroquinolones
What does it mean if an antimicrobial is time-dependent [concentration independent]?
- killing is predicted by the amount of time that concentration in body is above certain level [MIC]
- don’t get any more effectiveness by giving bigger dose at each time point, want to give doses more frequently
What are 2 examples of time-dependent drugs?
- b lactams
- glycopeptides [vancomycin]
What is the minimum inhibitory concentration [MIC]?
- lowest concentration of an antibiotic that will inhibit the visible growth of bacteria in vitro
What are 5 tests for antibiotic susceptibility
- broth macrodilution
- microdilution
- E test
- disk diffusion
- automated systems
What is mech of broth macrodilution?
- innoculate different concentrations of drug with same amount of bacteria
- let incubate 24 hours
- look for tubes with no turbidity [= no bacteria growth]
- MIC is the lowest antibiotic conc that has no turbidity
What is broth microdilution?
- uses idea of broth macrodilution but looking at multiple types of antibiotics as well as concentrations.
What is mech of E[psilometer] test?
- plate inoculated with bacteria
- lay down antibiotic-impregnanted strip with varying conc of antibiotic along the strip
- wait 24 hours
drug diffuses out from strip and inhibits bacterial growth - look for line where zone of inhibition ends to get min antibiotic conc that stops bacterial growth
What is mech of disk diffusion [kirby bauer] test?
- plate innoculated with bacteria
- put on antibiotic impregnated disk
- measure size of zone of inhibition around the disk [large zone is susceptible, small or no zone is resistant]
- qualitative not quantitative
- does not give MIC
How do you calculate MIC from disk diffusion?
- you can’t!
- you can only get qualitative information –> larger inhibition zone means more susceptible, smaller means resistant
What does bacteriostatic mean?
- arrests bacterial growth
- allows host immune system to kill bacteria
What does bactericidal mean?
- kills the bacteria
- eradicates infection in absence of host defense mech
Is linezolid bacteriostatic or bactericidal?
bacteriostatic
Are B lactams bacteriostatic or bactericidal?
bactericidal
Is vancomycin bacteriostatic or bactericidal?
both – it is bactericidal against some organisms and bacteriostatic against others
What is mech of action of B-lactams?
- interfere with bacterial cell wall synthesis
- bind penicillin binding proteins [PBPs] that are on cytoplasmic membrane
- inhibit transpeptidases
- prevent cross-linking of peptidoglycan
What are the 5 types of penicillins?
- natural penicillins
- anti-staphylococcal penicillins
- extended-spectrum [amino] penicillins
- anti-pseudomonal penicillins
- B-lactamase inhibitor combinations
What is the route of administration of penicillin?
- determined by how stable the drug is in presence of gastric acid –> if oral has to be stable
- most incompletely absorbed after oral administration
What is the one type of penicillin that is completely absorbed after oral administration?
amoxicillin
What is the half life like for penicillin? What does this mean for dose timing?
- short half-life so need to dose frequently
How is penicillin excreted normally? what is the one exception?
renal elimination
nafcillin is the exception – is not eliminated by renal
What are 4 main types of infections penicillin is used to treat?
- gram positive cocci, gram negative cocci, gram positive bacilli, spirochetes
What are 3 specific bacteria that penicillin is drug of choice for?
- streptococcus pyogenes [GAS]
- agalactiae [GBS]
- treponema pallidum [syphilis]
What is penicillin G?
intravenous penicillin [most important]
What is penicillin V?
oral penicillin –> stable in presence of acid
What are penicillinases? Whats a bacteria that they are commonly found in?
- penicillinases inactivate penicillin
- found in staphylococcus aureus
What are some examples of anti-staphylococal penicillins?
nafcillin [most important]
oxacillin
dicloxacillin
What is significant about anti-staphylococcal penicillins? How are they affected by penicillinase? what are they used to treat? are they active against gram negative?
- penicillinase resistant
- drug of choice for staph aureus skin or bloodstream infections
- no gram-negative activity
What is MSSA?
methicillin susceptible staph aureus
What are some examples of extended spectrum [amino] penicillins?
- ampicillin and amoxicillin [oral]
What is significant about extended spectrum penicillins? what are they used to treat? are they active against gram negative/positive/anaerobes?
- treat gram-positive organisms [GAS and GBS]
- better gram-negative activity than natural penicillin
- some anaerobic activity
- active against enterococci
What is ampicillin used to treat primarily?
listeria monocytogenes
What are two drugs of choice for strep throat [strep pyogenes]?
- penicillin
- amoxicillin
What 3 main things confer penicillin resistance?
- lack of peptidoglycan cell wall
- B lactamases
- decreased permeability to antibiotic
Why is mycoplasma inherently resistant to penicillin?
because mycoplasma lacks a cell wall –> penicillin works by attacking the cell wall so if no cell wall can’t attack
What do B-lactamases do? How can they be passed on?
- hydrolyzed B-lactam ring
- gene encoding enzyme transferred via plasmid from one bacteria to another
- major causes of resistance in gram negatives
What are two mechs of decreased permeability in bacterial cell wall to antibiotic?
- change in outer membrane porin so drug can’t enter
- efflux pump so drug is leaving get lower conc in cell
What is mech of altered penicillin target?
- get mutation in PBP to reduce affinity
- in MRSA get altered PBP [PBP2a] that lowers affinity for all B-lactams
What are 3 B-lactamase inhibitors?
- clavulanic acid
- sulbactam
- tazobactam
What do B-lactamase inhibitors do?
- contain a B-lactam ring
- bind to B lactamases and prevent them binding antibiotic
Which B-lactamase inhibitor do you pair with ampicillin to increase gram negative activity?
ampicillin and sulbactam
Which B-lactamase inhibitor do you pair with amoxicillin to increase gram negative activity?
amoxicillin and clavulanic acid
What is mech of hypersensitivity rxn to penicillin?
- penicilloic acid [penicillin metabolite] causes an immune rxn
- get hives –> angioedema –> anaphylaxis
Which patients get maculopapular rash from amoxicillin?
pts with EBV associated mononucleosis
Why does penicillin cause diarrhea?
- get alterations in commensal flora
- get clostridium difficile colitis
What is possible effect of penicillin on kidney
- interstitial nephritis
What is effect of penicillin on neuro?
causes neurotoxicitiy –> decreases seizure threshold
How are cephalosporins categorized?
- into 5 generations
- increased gram negative activity with higher generations
- 4th generation has good gram + and - activity