L27 - O'Keefe - Intro to Antibiotics Part 2 Flashcards
How does antibiotic selection differ for empiric vs directed/targeted therapy?
For directed therapy, since you know the organism and susceptibility, you can use a drug with a more narrow spectrum
*also, for directed therapy the antibiotic is given for a pre-defined duration
Compare the duration of therapy for the 2 causes of meningitis…
Meningitis due to strep pneumoniae = treat for 10-14 days
meningitis due to Niesseria meningitidis = 7 days
What are two types of therapies that can be employed for the use of antibiotics?
Prophylactic therapy and combination therapy
Define prophylactic therapy
antibiotics are give to PREVENT the development of infection
choose therapy based on drug of choice for the most probably organism and susceptibility patterns of the region
administer as long as the patient is at risk
Define Combination therapy (specifically…what are 3 things it can be used to do?)
- broaden bacterial coverage to all organisms causing infection
- decrease the emergence of resistance
- take advantage of synergy by using more than 1 antibiotic
What are two examples of prophylaxis (prevention) that were discussed in lecture?
peri-operative surgical prophylaxis
endocarditis prophylaxis
Explain peri-operative surgical prophylaxis
wound infections can be caused by skin flora
during operations, antibiotics are given against skin flora to reduce wound infection
explain endocarditis prophylaxis
to prevent endocarditis, antibiotic is given against oral flora for dental procedures
applies if person has a damaged or prosthetic heart valve or previous endocarditis
For both prophylaxis examples, what is the overall dosing regimen?
single dose given only
no benefit from prolonged antibiotic use
What are the 3 possible effects from combination therapy?
synergy
additive
antagonism
Define synergy
the antimicrobial effect of the two drugs together is greater than the additive activity of each one separately
(A + B) > A + B
Define additive
the antimicrobial activity of the drugs used together is equal to the sum of each one separately
(A + B) = A + B
Define antagonism
the antimicrobial activity of the drug combo is less than what you would expect from the addition of each one
(A + B)
Give an example of synergy
For enterococcal endocarditis:
penicillins don’t kill enterococcus, but if you add gentomyacin (aminoglycoside) you get rapid killing
Compare and contrast bacteriostatic vs bactericidal (definitions)
Bacteriostatic = antibiotic INHIBITS bacterial growth, killing depends on host defense mechanisms (to “cure” the infection)
Bactericidal = antibiotic KILLS bacteria, is less dependent on host defense mechanisms
*note: he said to know whether classes are bacteriostatic or bactericidal
What are disadvantages of bacteriostatic antibiotics?
If host defenses are inadequate, organisms that were only partially inhibited could survive/replicate and give a recurrent infection upon stopping use of the antibiotic (or if serum conc of the antibiotic go below the MIC)
Give an example where host defenses won’t be sufficient to get ride of infection
Endocarditis = infection on a clot in a valve
because there’s no blood supply to the clot, host defenses don’t reach it
What are examples of bacteriostatic antibiotics?
macrolides, ketolides, tetracyclines, glycylcylines, sulfonamides, clindamycin, Synercid, and linezolid
*note: he said to know whether classes are bacteriostatic or bactericidal
When would you want to use a bactericidal antibiotic (overall)?
it’s preferable if the host immune system is compromised or doesn’t function well (ex: neutropenia or immunosuppresion)
*remember: neutropenia = low neutrophil levels
Bactericidals are required for the treatment of…? (give 4 examples)
meningitis (host defenses aren’t effective in sub-arachnoid space)
endocarditis
osteomyelitis
febrile neutropenia
What are examples of bactericidal antibiotics?
penicillins, cephalosporins, carbanpenems, aztreonam, fluoroquinolones, aminoglycosides, vancomycin, daptomycin, Bactrim, and metronidazole
*note: he said to know whether classes are bacteriostatic or bactericidal
What is plotted for a pk graph? pd graph? pk/pd graph?
PK graph = conc vs time
PD graph = conc vs effect (aka dose response curve)
PK/PD graph = effect vs time
What are two important PD parameters for antibiotics?
AUC/MIC
Time above MIC
What is PAE?
Post-antibiotic effect
it’s the time it takes for the bacteria to re-grow once serum conc of antibiotic fall BELOW the MIC (is drug and organism specific!)
ex: sometimes the organism starts to grow immediately but sometimes there’s a gap (the gap is the PAE)
What is the benefit of a long PAE?
You can safely spread the dose out and allow serum concentrations to fall below MIC
Describe the PAE for gram positive bacteria
all antibiotics have some PAE
beta-lactams have a PAE of 2 hours
Describe the PAE for gram negative bacteria
prolonged PAEs seen with: protein or nucleic acid synthesis inhibitors (ex: aminoglycosides or fluoroquinolones)
Define concentration dependent killing
Get more rapid and extensive killing with higher serum concentrations…the higher the level of drug in serum, the more rapid the killing
Prolonged persistent effects (post-antibiotic)
Give an example of concentration dependent killing
Once daily aminoglycosides
give a high “once a day” dose and avoid toxicity
Define time dependent killing
killing depends on time of exposure above MIC (not higher serum concentrations)
seen with highly resistant organisms
How would dosing differ for time dependent killing?
can extend dosing (ex: infuse for 4 hours instead of 1) so the drug stays in the patient for a longer period of time even if the peak level is lower
*you’re increasing exposure of patient to a concentration of drug that’s effective against the organism
what is the general approach to the selection of an antimicrobial? (give 5 “steps”)
- confirm presence of infection
- select empiric therapy (start therapy before you know what the organism is)
- identify the pathogen
- modify/streamline the antibiotic therapy
- monitor therapeutic response
What are the 3 infection-specific parameters to consider when choosing an antibiotic?
- severity of infection
- site of infection
- infecting organism
(ex: don’t give orally for sepsis)
What are 6 host-specific factors to consider when choosing an antibiotic and why?
- allergies (and degree of cross-reactivity)
- age (elderly have dec renal function and thus maintain antibiotics for longer)
- pregnancy or nursing (potential effect on fetus and there’s also increased in Vd as well as renal clearance)
- rental and hepatic function
- concomitant drug therapy
- underlying disease states
Why is renal/hepatic function important for choosing antibiotics?
Diminished function may lead to drug accumulation and undue toxicity so you have to adjust doses
What antibiotics are primarily eliminated by the kidneys? (7)
most beta-lactams vancomycin aminoglycosides some fluoroquinolones Bactrim daptomycin tetracycline
What antibiotics are primarily eliminated/metabolized by the liver? (9)
macrolides Synercid linezolid clindamycin metronidazole some fluoroquinolones Bactrim doxycyline tigecycline
What is one example where you must consider concomitant drug therapy when choosing an antibiotic?
azoles for fungal infections inhibit the cyp system
ex: in the case of a kidney transplant, cyclosporins are given and azole would increase the levels of cyclosporins
what disease states may predispose patients to infection/pathogens?
diabetes and soft tissue infections
burns and skin infections
trauma patients
What are the 7 drug factors you must consider when choosing an antibiotic?
- in-vitro activity and current susceptibilities
- established clinical efficacy
- drug of choice charts
- PK and tissue penetration (MUST get sufficient concentrations at the site of infection)
- PD (type of bacterial activity needed for organism and infection type)
- side effect profiles
- cost
Which is more costly…IV or oral antibiotics?
IV
Monitoring serum concentrations and toxicity can be costly. This is done for which group of antibiotics?
Aminoglycosides
